Oxygen intercalation in PVD graphene grown on copper substrates: A decoupling approach.

We investigate the intercalation process of oxygen in-between a PVD-grown graphene layer and different copper substrates as a methodology for reducing the substrate-layer interaction. This growth method leads to an extended defect-free graphene layer that strongly couples with the substrate. We have found, by means of X-ray photoelectron spectroscopy, that after oxygen exposure at different temperatures, ranging from 280 °C to 550 °C, oxygen intercalates at the interface of graphene grown on Cu foil at an optimal temperature of 500 °C. The low energy electron diffraction technique confirms the adsorption of an atomic oxygen adlayer on top of the Cu surface and below graphene after oxygen exposure at elevated temperature, but no oxidation of the substrate is induced. The emergence of the 2D Raman peak, quenched by the large interaction with the substrate, reveals that the intercalation process induces a structural undoing. As suggested by atomic force microscopy, the oxygen intercalation does not change significantly the surface morphology. Moreover, theoretical simulations provide further insights into the electronic and structural undoing process. This protocol opens the door to an efficient methodology to weaken the graphene-substrate interaction for a more efficient transfer to arbitrary surfaces.

Precisely controlled fabrication, manipulation and in-situ analysis of Cu based nanoparticles.

The increasing demand for nanostructured materials is mainly motivated by their key role in a wide variety of technologically relevant fields such as biomedicine, green sustainable energy or catalysis. We have succeeded to scale-up a type of gas aggregation source, called a multiple ion cluster source, for the generation of complex, ultra-pure nanoparticles made of different materials. The high production rates achieved (tens of g/day) for this kind of gas aggregation sources, and the inherent ability to control the structure of the nanoparticles in a controlled environment, make this equipment appealing for industrial purposes, a highly coveted aspect since the introduction of this type of sources. Furthermore, our innovative UHV experimental station also includes in-flight manipulation and processing capabilities by annealing, acceleration, or interaction with background gases along with in-situ characterization of the clusters and nanoparticles fabricated. As an example to demonstrate some of the capabilities of this new equipment, herein we present the fabrication of copper nanoparticles and their processing, including the controlled oxidation (from Cu0 to CuO through Cu2O, and their mixtures) at different stages in the machine.

Adsorption and Coupling of 4-aminophenol on Pt(111) surfaces.

We have deposited 4-aminophenol on Pt(111) surfaces in ultra-high vacuum and studied the strength of its adsorption through a combination of STM, LEED, XPS and ab initio calculations. Although an ordered (2√3×2√3)R30° phase appears, we have observed that molecule-substrate interaction dominates the adsorption geometry and properties of the system. At RT the high catalytic activity of Pt induces aminophenol to lose the H atom from the hydroxyl group, and a proportion of the molecules lose the complete hydroxyl group. After annealing above 420K, all deposited aminophenol molecules have lost the OH moiety and some hydrogen atoms from the amino groups. At this temperature, short single-molecule oligomer chains can be observed. These chains are the product of a new reaction that proceeds via the coupling of radical species that is favoured by surface diffusion.

125I-Antisauvagine-30: a novel and specific high-affinity radioligand for the characterization of corticotropin-releasing factor type 2 receptors.

Corticotropin-releasing factor (CRF) receptors type 1 (CRF(1)) and type 2 (CRF(2)) differ from each other in their pharmacological properties. The human and ovine CRF versions bind to CRF(1) receptors with significantly higher affinity than to CRF(2) receptors. Recently antisauvagine-30, an N-terminally truncated version of the CRF analog sauvagine, was characterized as a specific antagonist to mouse CRF(2B). We have synthesized the radiolabeled version (125)I-antisauvagine-30 and tested it for its affinity at human CRF(1) (hCRF(1)), hCRF(2A), Xenopus CRF(1) (xCRF(1)) and xCRF(2) receptors. In control binding studies (125)I-labeled hCRF, sauvagine and astressin were also bound to these receptors. (125)I-antisauvagine-30 exclusively bound to hCRF(2A) and xCRF(2) but not to hCRF(1) and xCRF(1) receptors. (125)I-antisauvagine-30 binding to hCRF(2A) and xCRF(2) receptors was saturable and of high affinity (hCRF(2A): K(d)=125 pM; xCRF(2): K(d)=1.1 nM). In displacement binding experiments using (125)I-antisauvagine-30 as radioligand several CRF analogs bound to hCRF(2A) and xCRF(2) receptors with similar rank orders as reported with other CRF radioligands. Finally, preliminary studies using (125)I-antisauvagine-30 binding to membrane homogenates prepared from different rat brain structures showed that the peptide bound specifically to brain areas expressing CRF(2) receptors. These data demonstrate that (125)I-antisauvagine-30 is the first high-affinity ligand to specifically label CRF(2) receptors.

Characterization of [(3)H]Quisqualate binding to recombinant rat metabotropic glutamate 1a and 5a receptors and to rat and human brain sections.

We have investigated the binding properties of [(3)H]quisqualate to rat metabotropic glutamate (mGlu) 1a and 5a receptors and to rat and human brain sections. Saturation isotherms gave K:(D) values of 27 +/- 4 and 81 +/- 22 nM: for mGlu1a and mGlu5a receptors, respectively. Several compounds inhibited the binding to mGlu1a and mGlu5a receptors concentration-dependently. (S:)-4-Carboxyphenylglycine, (S:)-4-carboxy-3-hydroxyphenylglycine, and (R,S)-1-aminoindan-1,5-dicarboxylic acid, which completely inhibited [(3)H]quisqualate binding to the mGlu5a receptor, were inactive in a functional assay using this receptor. The distribution and abundance of binding sites in rat and human brain sections were studied by quantitative receptor radioautography and image analysis. Using 10 nM: [(3)H]quisqualate, a high density of binding was detected in various brain regions with the following rank order of increasing levels: medulla, thalamus, olfactory bulb, cerebral cortex, spinal cord dorsal horn, olfactory tubercle, dentate gyrus molecular layer, CA1-3 oriens layer of hippocampus, striatum, and cerebellar molecular layer. The ionotropic component of this binding could be inhibited by 30 microM: kainate, revealing the distribution of mGlu1+5 receptors. The latter were almost completely inhibited by the group I agonist (S:)-3,5-dihydroxyphenylglycine. The binding profile correlated well with the cellular sites of synthesis and regional expression of the respective group I receptor proteins revealed by in situ hybridization histochemistry and immunohistochemistry, respectively.

[3H]ATPA: a high affinity ligand for GluR5 kainate receptors.

The pharmacological properties of [3H]ATPA ((RS)-2-amino-3(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid) are described. ATPA is a tert-butyl analogue of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid) that has been shown to possess high affinity for the GluR5 subunit of kainate receptors. [3H]ATPA exhibits saturable, high affinity binding to membranes expressing human GluR5 (GluR5) kainate receptors (Kd approximately 13 nM). No specific binding was observed in membranes expressing GluR2 and GluR6 receptors. Several compounds known to interact with the GluR5 kainate receptor inhibited [3H]ATPA binding with potencies similar to those obtained for competition of [3H]kainate binding to GluR5. Saturable, high affinity [3H]ATPA binding (Kd approximately 4 nM) was also observed in DRG neuron (DRG) membranes isolated from neonatal rats. The rank order potency of compounds to inhibit [3H]ATPA binding in rat DRG and GluR5 membranes were in agreement. These finding demonstrate that [3H]ATPA can be used as a radioligand to examine the pharmacological properties of GluR5 containing kainate receptors.

Binding characteristics of a potent AMPA receptor antagonist [3H]Ro 48-8587 in rat brain.

A new AMPA receptor antagonist, Ro 48-8587, was characterized pharmacologically in vitro. It is highly potent and selective for AMPA receptors as shown by its effects on [3H]AMPA, [3H] kainate, and [3H] MK-801 binding to rat brain membranes and on AMPA- or NMDA-induced depolarization in rat cortical wedges. [3H]Ro 48-8587 bound with a high affinity (KD = 3 nM) to a single population of binding sites with a Bmax of 1 pmol/mg of protein in rat whole brain membranes. [3H]Ro 48-8587 binding to rat whole brain membranes was inhibited by several compounds with the following rank order of potency: Ro 48-8587 > 6-nitro-7-sulphamoylbenzo[f] quinoxaline-2,3-dione (NBQX) > YM 90K > 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) > quisqualate > AMPA > glutamate > kainate > NMDA. The distribution and abundance of specific binding sites (approximately 95% of total) in sections of rat CNS, revealed by quantitative receptor radioautography and image analysis, indicated a very discrete localization. Highest binding values were observed in cortical layers (binding in layers 1 and 2 > binding in layers 3-6), hippocampal formation, striatum, dorsal septum, reticular thalamic nucleus, cerebellar molecular layer, and spinal cord dorsal horn. At 1 nM, the values for specific binding were highest in the cortical layers 1 and 2 and lowest in the brainstem (approximately 2.6 and 0.4 pmol/mg of protein, respectively). Ro 48-8587 is a potent and selective AMPA receptor antagonist with improved binding characteristics (higher affinity, selectivity, and specific binding) compared with those previously reported.

Characterization of binding of [3H]PD 128907, a selective dopamine D3 receptor agonist ligand, to CHO-K1 cells.

PD 128907 [4a R, 10 b R-(+)-trans-3, 4, 4a, 10 b - tetrahydro - 4- n -propyl2 H,5H-[1]benzop-yrano[4,3-b]1,4-oxazin-9-ol.], a selective dopamine (DA) D3 receptor agonist ligand exhibits about a 1000-fold selectivity for human D3 receptors (Ki, 1 nM) versus human D2 receptors (Ki, 1183 nM) and a 10000-fold selectivity versus human D4 receptors (Ki, 7000 nM) using [3H]spiperone as the radioligand in CHO-K1-cells. Studies with [3H]PD 128907, showed saturable, high affinity binding to human D3 receptors expressed in CHO-K1 cells (CHO-K1-D3) with an equilibrium dissociation constant (Kd) of 0.99 nM and a binding density (Bmax) of 475 fmol/mg protein. Under the same conditions, there was no significant specific binding in CHO-K1-cells expressing human D2 receptors (CHO-K1-D2). The rank order of potency for inhibition of [3H]PD 128907 binding with reference DA agents was consistent with reported values for D3 receptors. These results indicate that [3H]PD 128907 is a new, highly selective D3 receptor ligand with high specific activity, high specific binding and low non-specific binding and therefore should be useful for further characterizing the DA D3 receptors.

Frequency of early-morning rise in blood glucose in children with diabetes at camp.

To estimate the frequency of an early-morning glucose rise (EMR) in relatively unselected children with insulin-dependent diabetes mellitus (IDDM), we assessed capillary blood glucose (CBG) at midsleep (0200-0430) and prebreakfast (0700-0800) in 97 children with diabetes at camp. The EMR (prebreakfast CBG-midsleep CGB) was inversely related to the midsleep CBG level (r = -.45, P less than .001). Of the 49 children with midsleep CBG less than 200 mg/dl, the mean EMR was 34 +/- 60 mg/dl, and 18 of these children had rises of greater than 40 mg/dl. In conclusion, when midsleep glycemia is less than 200 mg/dl, a rise in blood glucose from midsleep to prebreakfast, often greater than 40 mg/dl, is a common element of glycemic control among children with IDDM. The relative importance of the Somogyi phenomenon, the dawn phenomenon, and mere insulin insufficiency in the early-morning hours cannot be determined from these data.

The intravenous insulin tolerance test in type I diabetes.

The intravenous insulin tolerance test (ITT) allows general assessment of insulin sensitivity by determining the fall in plasma glucose after injection of 0.1 unit/kg regular insulin. To evaluate the usefulness of this test diagnostically in distinguishing Type I from Type II diabetes, 24 patients with Type I diabetes (defined as early age of onset, ideal body weight or less at onset, and insulin dependence) underwent ITTs. Seven patients had normal glucose disposal rates (Ki greater than or equal to 2.5. Nine patients had Ki less than 2.5 but greater than 1.0. Eight patients had Ki less than 1.0. The slopes did not correlate with the control of the diabetes (as assessed by measurement of glycosylated hemoglobin), the presence or titer of anti-insulin antibodies, the duration of the diabetes, the age of onset, the presence of complications, or the current insulin dose. These results indicate that varying amounts of insulin resistance may be present in Type I diabetes and cannot necessarily be explained by poor control or the presence of insulin antibodies.

Genetic transmission of tumoral calcinosis: autosomal dominant with variable clinical expressivity.

Tumoral calcinosis is a rare inherited metabolic disorder characterized by hyperphosphatemia, elevated serum 1,25-dihydroxyvitamin D levels and periarticular cystic and solid calcifications. Based on previous investigations, the inheritance of this disorder has been postulated to be autosomal recessive. This interpretation was based on finding clinically affected subjects in only single generations of kindreds. We investigated four generations of an affected kindred and found nine subjects with the disease. A unique dental lesion which is specific for this disorder and serves as a phenotypic marker was identified in two generations of the kindred. In all affected subjects, elevated serum 1,25-dihydroxyvitamin D levels were found, although each member did not have the classical clinical findings of tumoral calcinosis. The possibility that this disorder may be variably expressed and have multiple formes frustes has not been previously considered. Using the unique dental lesion as well as the classical clinical and biochemical abnormalities, we found that in this kindred, tumoral calcinosis is transmitted in an autosomal dominant mode, with variable clinical expressivity.

The flashlight test lacks validity as a screen for nocturnal hypoglycemia.

Though never validated, the flashlight test is a commonly used screen for nocturnal hypoglycemia. Between 2 a.m. and 4 a.m., we applied the test to 107 children at Eagle's Nest Camp for Children with Diabetes. We validated the test against simultaneously determined capillary blood glucose values (Glucoscan). An eyelid squint in response to the flashlight was considered an intact test. No significant difference existed between mean glucoses for intact and nonintact responses. Both sensitivity and positive predictive value are too low for the flashlight test to be useful in screening for nocturnal hypoglycemia.

Parent-peer influence as a predictor of marijuana use.

Although there is some literature which discusses adolescent reference groups, none have utilized reference group theory to examine the relative impact of the parent and peer reference groups and to attempt to predict behavior among teenagers from this knowledge. This study attempts to correct this deficiency by examining the frequency of marijuana use in a nonrandom sample of college students from a large southwestern university. Ordinal type scales and tau-b provide a statistically strong degree of association between the type of reference group orientation and marijuana use. The results of this study show that the influence of the most salient reference group appears to be an important predictor of whether or not an individual may engage in the use of marijuana.

Performance of technical skills of diabetes management: increased independence after a camp experience.

This study examines some educational effects of a camp experience on independent performance of tasks in the management of diabetes mellitus. One hundred and eleven children were studied with regard to insulin administration, urine glucose testing, recognition of hypoglycemic reactions, adherence to diet, and over-all independence. There was a significant increase in independent measurement of insulin dose, administration of insulin injections, and urine glucose testing. No significant differences were seen in dietary adherence of ability to recognize hypoglycemic reactions. Precamp data indicated that returning campers demonstrated greater independence in insulin administration prior to camp than did new campers. After camp, both new and returning campers showed significant increases in independent performance of dose measurement and injection. It is concluded that a camp educational experience contributes to both the knowledge and performance of self-care techniques required in the management of diabetes mellitus.

Parathyroid autotransplantation in primary parathyroid hyperplasia.

Four patients with primary parathyroid hyperplasia were treated by total parathyroidectomy and autotransplantation of parathyroid tissue into the forearm muscle. All patients remained normocalcemic after vitamin D and oral calcium replacement therapy were stopped at 1 1/2, four, nine and 13 months, respectively. Graft function was documented further by detection of a higher concentration of parathyroid hormone in plasma from the basilic vein draining the graft bed than from the basilic vein in the contralateral arm. Intravenous calcium infusion suppressed parathyroid hormone secretion from the graft whereas hypocalcemia induced by ethylenediaminetetra-acetic acid markedly stimulated hormone release. In two patients histologic examination of a grafted fragment revealed hyperplastic parathyroid tissue. This method of treatment offers a suitable alternative to radical subtotal parathyroidectomy in selected patients with hyperparathyroidism.

The early diagnosis of medullary carcinoma of the thyroid gland in patients with multiple endocrine neoplasia type II.

Pentagastrin is a potent stimulator of thyrocalcitonin secretion from "C" cells. Since medulllary carcinoma of the thyroid gland (MCT) is a tumor composed of "C" cells, pentagastrin was used to screen a large kindred with multiple endocrine neoplasia type II (MCT, pheochromocytoma (s), and parathyroid hyperplasia). Four children with no thyroid abnormalities evident on physical examination, with negative thyroid scans, and with normal levels of plasma thyrocalcitonin both before and after calcium infusion, were found to have elevated peripheral levels of this hormone following pentagastrin injection. All four children were found to have very small foci of MCT, in both thyroid lobes at the time of total thyroidectomy. Pentagastrin stimulation used conjointly with selective catheterization of the inferior thyroid vein provided even greater diagnostic accuracy in detecting elevations in thyrocalcitonin secretion. This test has great diagnostic utility, especially in screening patients with multiple endocrine neoplasia type II.