Laser-writable high-k dielectric for van der Waals nanoelectronics.

Similar to silicon-based semiconductor devices, van der Waals heterostructures require integration with high-k oxides. Here, we demonstrate a method to embed and pattern a multifunctional few-nanometer-thick high-k oxide within various van der Waals devices without degrading the properties of the neighboring two-dimensional materials. This transformation allows for the creation of several fundamental nanoelectronic and optoelectronic devices, including flexible Schottky barrier field-effect transistors, dual-gated graphene transistors, and vertical light-emitting/detecting tunneling transistors. Furthermore, upon dielectric breakdown, electrically conductive filaments are formed. This filamentation process can be used to electrically contact encapsulated conductive materials. Careful control of the filamentation process also allows for reversible switching memories. This nondestructive embedding of a high-k oxide within complex van der Waals heterostructures could play an important role in future flexible multifunctional van der Waals devices.

Effect of low temperatures on glucose-induced insulin secretion and glucose metabolism in isolated pancreatic islets of the rat.

The direct effect of hypothermia on the inhibition of insulin secretion may result from inhibition of the availability of energetic substrates and/or the lack of metabolic signals. In order to verify this hypothesis, the insulin secretion and the main metabolic glucose pathways were measured during the incubation of rat islets. In the presence of 16.7 mmol glucose/l and at 37 degrees C, insulin secretion was 925 +/- 119 microU/2 h per ten islets. With the same experimental conditions, glucose utilization, determined as the formation of 3H2O from [5-3H]glucose was 2225 +/- 184 pmol/2 h per ten islets, glucose oxidation measured as the formation of 14CO2 from [U-14C]glucose was 673 +/- 51 pmol/2 h per ten islets, pentose cycle determined as the formation of 14CO2 from either [1-14C]glucose or [6-14C]glucose was 37 +/- 5 pmol/2 h per ten islets; glucose oxidation by the tricarboxilic acid cycle, calculated to be the difference between glucose oxidation and pentose cycle values, was 636 pmol/2 h per ten islets. Hypothermia highly inhibited glucose-induced insulin secretion and glucose utilization. Inhibition of insulin secretion was partial at 27 degrees C since it was 2.5 times lower than that at 37 degrees C, and it was complete at 17 degrees C. Glucose oxidation in the tricarboxilic acid cycle was markedly inhibited by hypothermia since the inhibition coefficient (Q10) between 37 and 27 degrees C was 5. In contrast, glucose oxidation in the pentose phosphate shunt was enhanced at 27 degrees C, reaching 92 +/- 17 pmol/2 h per ten islets, and it was inhibited relatively little at 17 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of low temperatures on glucose-induced insulin secretion and ionic fluxes in rat pancreatic islets.

The direct effect of cold on the inhibition of B cell secretion is well known in hibernating and experimentally hypothermic mammals. This temperature dependency may result from the inhibition of ion transport across the membranes. In order to verify this hypothesis, ionic effluxes and insulin secretion from rat islets loaded with 86Rb+ and 45Ca+ were measured during perifusion. At 37 degrees C, the rise in glucose concentration from zero to 16.7 mmol/l provoked a rapid decrease in 86Rb+ efflux, an early fall and subsequent rise in 45Ca2+ efflux and a typical biphasic pattern of insulin secretion. At 27 degrees C, glucose induced only a very slight increase in insulin secretion, while the fluxes of radioactive ions were not significantly modified in amplitude but were clearly delayed. At 17 degrees C, no insulin response to glucose was observed and the decrease in K+ conductance indicated by 86Rb+ flux decrease was less temperature-dependent than the movement of Ca2+. After supplementary stimulation with a high extracellular concentration of Ca2+, insulin secretion was enhanced at 27 degrees C and reached levels induced by glucose alone at 37 degrees C. An increase in hormone secretion occurred even at 17 degrees C, but only during a first phase of secretion. Regular increases in temperature potentiated insulin secretion and provoked changes in ionic fluxes which suggest that B cell depolarization (86Rb+ flux decrease) induced by glucose can occur at 15 degrees C but cannot induce the opening of voltage-dependent Ca2+ channels (increase in 45Ca2+ efflux) until temperatures higher than 27 degrees C are reached.(ABSTRACT TRUNCATED AT 250 WORDS)

Lung hysteresis: a morphological view.

The lung is an imperfect elastic body and for this reason dissipates energy. The energy applied to the lung in inspiration is not recovered in expiration. The property of dissipating energy receives the name of hysteresis. Lung hysteresis can be quantified because it applies to the area between the ascending and descending portions of the pressure-volume curve. Lung hysteresis comprises parenchymal hysteresis and bronchial hysteresis. Each point on the pressure-volume applies to a different morphology of the lung parenchyma. The changes that take place in the lung architecture during expiration are related to alveolar recruitment: in inspiration the lung volume increases by the opening of distal air units. In expiration the lung volume decreases due to derecruitment. The energy is dissipated mainly in the alveolar recruitment process, in which forces of molecular adhesion, such as surface tension, are at work. Bronchial hysteresis involves the dead space and the bronchial wall being greater in expiration.

Pressure volume curve and alveolar recruitment/de-recruitment. A morphometric model of the respiratory cycle.

HYPOTHESIS: The changes in pulmonary volume taking place during respiration are accompanied by the opening and closing of the alveoli, with the number of alveoli open, at the same transpulmonary pressure (TPP) differing, depending on whether the lung is insufflated or deflated. MATERIAL AND METHODS: Seventy 344 Fischer rats divided into five groups. Group 1 lungs were fixed by instilling 10% formalin through the trachea to a pressure of 25 cm H2O. The lungs of the next four groups were air-filled and fixed via the pulmonary artery: group 2 lungs were fixed in inflation at 10 cm H2O TPP; group 3 lungs were fixed in inflation at 20 cm. H2O TPP; the lungs of groups 4 and 5 were fixed in deflation and, therefore, were inflated with air up to 27 cm. H2O to drop to 20 cm in group 4 and to 10 cm in group 5. The lungs were processed for light microscopy, carrying out a morphometric study. The results were statistically processed. RESULTS: The lungs insufflated with liquid fixative at 25 cm of TPP reached higher values in the variables Pulmonary Volume, Internal Alveolar Surface (IAS) and Number of Alveoli, being statistically significant (p < 0.05) in comparison with the other four groups. In the lungs fixed in deflation, the pulmonary volume, IAS and number of alveoli were greater than in those fixed in inflation. The lungs fixed to 20 cm in deflation displayed significant statistical differences compared with those fixed to 20 cm in inflation. The IAS and number of alveoli gave good rates in relation with the pulmonary volume (r > or = 0.65). Three variables were used to measure the size of the alveoli, alveolar cord, alveolar surface and Lm, but none showed significant modifications. CONCLUSION: This study supports the hypothesis that changes in lung volume are related to the increase/decrease in the number of alveoli that are open/closed and not to the modification in the size of the alveoli. Alveolar recruitment is the microscopic expression of pulmonary hysteresis, since the number of alveoli open in deflation is greater than the number open during inflation.

Morphological hysteresis of the small airways.

The resistance to airflow that develops in most obstructive processes takes place in the small airways. The aim of the present paper is to describe bronchial hysteresis morphometrically in a respiratory cycle model. As a working hypothesis, it is proposed that the changes that take place in the respiratory tract during the respiratory cycle are related to the bronchial size. Specimen rat lungs were organized into five groups: In the first group, the lungs were filled with a liquid fixative to 25 cm of H2O transpulmonary pressure. The following four groups were inflated with air and fixed through the pulmonary artery. Groups 2 and 3 were fixed at 10 and 20 cm transpulmonary pressure in inflation. The last two groups were fixed in deflation and, for this purpose, the transpulmonary pressure was increased to 27 cm and decreased to 20 and 10 cm, respectively. The lungs were processed for morphometrical study and the following variables were quantified: pulmonary volume, internal area, internal perimeter, wall area, internal area radius and bronchial wall radius. The diameter of the airways studied varied between 84.06 microm and 526.4 microm. The results were classified into three subgroups consisting of small, medium-sized and large bronchi. With a single exception--the internal area in the medium-sized bronchi inflated to 20 cm--all the results obtained in deflation were higher than those obtained in inflation. The internal area increased or decreased significantly upon raising or lowering the transpulmonary pressure respectively, in the small and medium-sized bronchi. The wall area in the large bronchi showed significant differences between inflation and deflation at 10 and 20 cm transpulmonary pressure. The wall area was modified significantly in the lungs fixed at 20 cm in the small bronchi and at 10 cm in medium-sized bronchi. The bronchial wall radius was significantly greater in the large bronchi and smaller in the small bronchi. The lumen of the medium-sized and small bronchi increases in inspiration and decreases in expiration. The wall thickness displayed differences between inflation and deflation. The most marked hysteresis was presented by the bronchial wall in the large bronchi. Our results suggest that the behavior of the bronchi varies according to their size.

Age and experimental obstructive emphysema. A morphometrical study on the rat.

Age, as a risk factor in the development of experimental obstructive emphysema, is proposed as the hypothesis of this study. Ninety-two Wistar rats were organized into two age groups: adult (16 weeks) and middle-aged (56 weeks). Each age group was subdivided into three groups: a control group, consisting of unmanipulated animals; a "cannula" group consisting of animals into whose trachea a cannula was implanted; and a "valve" group, consisting of animals into whose trachea a valve had been implanted. The survival was one month. A histomorphometric study was performed on the lungs and the results were compared statistically. Throughout the experiment the amount of food consumed by each animal and the variations in weight were monitored. After sacrifice, the lungs were processed for light microscopy. Thirteen histomorphometric variables were quantified and subsequently systematized into three groups: those which quantified the size of the distal airspace ("area of the alveolar section", "alveolar chord" and "mean linear intercept"): those which quantified the tissue ("wall thickness", "tissue density", "internal perimeter of each alveolar section", "internal alveolar perimeter per field" and "alveolar section/section perimeter"); and those which quantified the elastic fibre ("elastic fibre area", "elastic fibre perimeter", "elastic fibre area/elastic fibre perimeter", "elastic fibre density" and "elastic fibre density per tissue density"). The results were compared statistically and the sensitivity, specificity and misclassification indices were calculated, as well as the attributable and relative risk. From the results, it was observed that, in general, the animals of the valve and cannula groups in both age groups displayed a decrease in food intake and a body weight loss. The middle-aged animals were the only group which displayed significant differences in all the morphometric variables except wall thickness, when the cannula and valve groups were compared with the control group. In both the cannula and valve groups, the values of the variables which quantified the distal airspace increased, while the values of the variables which quantified the lung tissue and the elastic fibre decreased. In the manipulated middle-aged group, the attributable risk of developing emphysema was 56.66% and the relative risk 5.55; in the group of manipulated adult animals, the attributable risk was 23.55% and the relative risk 1.66. The results of this study lead us to propose that the middle-aged rats with experimental airflow obstruction displayed a greater risk of developing emphysema than the adult rats which were subjected to the same procedure.

Pulmonary response to bovine albumin. A morphometric study in rats.

The following hypothesis is proposed: that hypersensitivity pneumonitis (HP), experimentally induced in rats, is the cause of a thickening in the alveolar wall, a decrease in the size of the alveole, hyperplasia in the bronchus-associated lymphoid tissue (BALT) and hypertrophy in the goblet cells. Wistar rats were classified into two different groups, namely, non-treated animals and animals exposed to bovine albumin (BA). A morphometric study was carried out and the following variables were quantified: a) percentage of lymphocytes, neutrophils and alveolar macrophages of the bronchio-alveolar lavage (BAL); b) the interstice of the alveole, the alveolar chord length, the alveolar wall thickness and the number of alveolar macrophages with hemosiderin within its cytoplasm; c) the size of lymphatic area (LA) in BALT, the length of the lymphatic epithelium (LEp) in BALT and the percentage of goblet cells in the bronchial epithelium. The following results were obtained from the animals exposed to BA: 1) a significant increase in both lymphocytes and neutrophils of BAL, and of alveolar macrophages with hemosiderin in its cytoplasm; 2) a significant thickening of the alveolar walls and the BALT elements, which confirms the above mentioned hypothesis; 3) a significant increase in the alveolar chord and a significant decrease in the number of goblet cells of the bronchus, which contradicts the above mentioned hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Tobacco smoke and age as risk factors in emphysema. Morphometrical study on the rat.

During ageing, a progressive deterioration in the pulmonary function, which can be accelerated by exposure to tobacco smoke, takes place. The hypothesis that the initial age of exposure to tobacco smoke is a factor of utmost importance in the development of emphysema is proposed. Eighty-six rats, aged nineteen months at the time of sacrifice, were used and were ordered into three groups: the first group consisted of unmanipulated animals; the second, of animals which had been exposed to tobacco smoke from the age of twelve months to the age of nineteen months; and the third, of animals which had been exposed to tobacco smoke from the age of nine months to the age of twelve months. The lungs of the animals were histologically processed for light microscopy and were studied morphometrically by computer. Eleven quantitative variables were quantified and ordered into three groups: variables related with alveolar enlargement; variables related with tissue loss; and variables related with the elastic fibre. The number of animals in which alveolar enlargement and tissue destruction concurred was counted, thus enabling the attributable and relative risks of developing emphysema to be calculated in the two groups of manipulated animals. From the results it is clear that, when compared with the unmanipulated group, the two groups which had been exposed to tobacco smoke displayed an increase in the variables which quantified alveolar enlargement and a decrease in those which measured tissue loss; these results were more significant in the third group (p < 0.001) than in the second (p < 0.05); significant differences were also found between these two groups of animals. The relative risk and attributable risks of developing emphysema were 2.41 and 28.15 respectively in the second group and 3.48 and 34.48 in the third group. Our results lead us to propose that the risk of developing emphysema exists in inverse proportion to the initial age of exposure to tobacco smoke.

Goodpasture's syndrome in aging. An experimental study on the rat. I.

The following hypothesis is proposed: Experimental lung disease in old rats is different from this disease in adult rats. In order to demonstrate this, we performed a morphometrical evaluation of the pulmonary state of two groups of rats at different ages and to which Goodpasture's syndrome had been induced. 115 Wistar rats were used. They were divided into four different groups as follows: 1) Healthy adult rats which had not been subjected to treatment; 2) diseased adult rats to which antipulmonary serum had been administered; 3) healthy old rats; and 4) diseased old rats. With the help of a computerized system, the length of the alveolar chord, the thickness of the alveolar wall and the surface of the bronchial-associated lymphoid tissue in each group was calculated. We also counted the number of alveolar macrophages (AM) with haemosiderin, the percentage of goblet bronchial cells and that of AM, lymphocytes and polymorphonuclear leukocytes of the broncho-alveolar lavage (BAL). The following results were obtained. When related to the diseased adult rats, the diseased old rats showed an increase in the alveolar chord and a decrease in the thickness of the alveolar wall, as well as in the number of AM with haemosiderin, goblet cells and BAL lymphocytes. These results support the proposed hypotheses, since the diseased adult animals showed signs of alveolar inflammation with interstitial edema, while in the diseased old animals these results are compatible with emphysema.

Goodpasture's syndrome in aging. An experimental study on the rat. II.

The following hypothesis is suggested: if a lung disease is induced in an adult rat, then its lung, in the senile age, will be different from what is considered to be a normal senile lung. In order to demonstrate this, the pulmonary state of two groups of old rats, one of which had suffered from Goodpasture's syndrome in the adult age has been assessed morphometrically. Fifty-three Wistar rats were used. They were divided into two groups: 1) healthy old rats; and 2) diseased old rats. Antipulmonary serum was administered to the latter and they were sacrificed a year later. Making use of a computing system, we calculated the following data for each group: the alveolar chord length, the alveolar wall thickness and the surface of the bronchial-associated lymphoid tissue (BALT). The alveolar macrophages (AM) with haemosiderin which were found in the lung tissue were also counted and the percentage of goblet bronchial cells and that of bronchoalveolar lavage (BAL) cells was also assessed. From the results, the following points should be emphasized: in diseased old rats, an increase in the alveolar chord, a decrease in lymphocytes with an increase in the AM of the BAL, and a decrease in goblet cells and AM with haemosiderin occur, all of which are significant when these rats are compared to healthy old rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein distribution in plasma HDL subfractions in alcohol consumers.

Alcohol intake is known to increase plasma HDL subfractions and apo A levels. Few data are available, however, with regard to precise apoprotein composition of plasma lipoproteins in alcohol consumers. The aim of the present study was to examine the lipid and apoprotein distribution in plasma lipoproteins of subjects with different levels of alcohol intake. Thirty-six male regular drinkers were classified as social (n = 10, average daily consumption greater than or equal to 5 and less than or equal to 20 g), moderate (n = 11, average daily consumption greater than 20 g and less than 70 g) and heavy drinkers (n = 15, average daily consumption greater than or equal to 70 g). Reference data were obtained from 11 subjects, all lifelong abstainers. Lipoproteins were fractioned by sequential ultracentrifugation and apolipoprotein distribution in VLDL, HDL-2 and HDL-3 was determined by isoelectrofocusing in polyacrylamide-urea gel. HDL-2 cholesterol was significantly higher in heavy drinkers (P less than 0.005). A parallel trend for HDL-3 cholesterol was observed. In alcohol consumers HDL-2 particles were enriched in apos C, in particular apo C-II (P 0.005), displacing apo A-I. These data suggest that apolipoprotein distribution in the HDL-2 subfraction is influenced by alcohol intake even at the lowest level.

[A morphometric model of hypersensitivity pneumonitis in the aging rat]. / Un modelo morfométrico de neumonitis por hipersensibilidad en la rata vieja.

Our objective was to develop an experimental model of hypersensitivity pneumonitis in the aging rat. The following hypothesis was proposed: hypersensitivity pneumonitis in the aging rat will be evident in alterations in cells harvested by bronchoalveolar lavage (BAL) and in an increase in alveolar interstitial tissue. Sixty animals with a mean age of 18 months were divided into 2 groups. Group 1 contained healthy, untreated animals and group 2 contained unhealthy animals that had been exposed to bovine seralbumin (BS). BAL and morphometric analysis of the lung was performed. The percentage of lymphocytes, polymorphonuclear, leukocytes and alveolar macrophages were determined in BAL. The morphometric variables studied were mean linear intersection (Lm), length of alveolar cord, wall thickness, tissue density and number of measurements of alveolar cord. The results show that the unhealthy animals had higher (p < 0.001) percentages of lymphocytes in BAL, lower Lm, diminished alveolar cord and thinner walls, as well as greater tissue density and a higher number of measurements. All differences were statistically significant (p < 0.001). These results lead to the conclusion that exposure of the aging rat to BS produces an increase in lymphocytes in BAL and an increase in interstitial alveolar content, findings that are related to alveolar-interstitial inflammation.

[Modifications in the composition of plasma HDLs in non-insulin-dependent diabetics]. / Modificaciones en la composición de las HDL plasmáticas en diabéticos no insulin dependientes.

The levels of plasmatic lipids and the lipo and apoprotein composition of lipoprotein of high density were analysed in 18 patients, diagnosed as having non-insulin dependent diabetes, and compared to a control group of 18 healthy patients. 10 patients showed a moderate hypertriglyceridemia, this sub-group having the main HDL alteration. In this lipoprotein fraction an increase of triglycerides was observed, and a decrease in cholesterol and apoprotein III, probably as result of a lower activity of lipoprotein lipase in plasma.

[Cardiovascular risk factors in an Arab and Hispanic working population]. / Factores de riesgo cardiovascular en una población laboral árabe e hispana.

318 records of male workers, 169 Spanish and 149 Arab were retrospectively studied in 1987 at the "Gabinete de Seguridad e Higiene en el Trabajo" (Council for Safety and Hygiene in the Workplace) in Ceuta in order to prove the hypothesis that 2 different ethnic groups living in the same geographic area have a non-equal distribution of cardiovascular risk factors. The Spanish group showed a higher prevalence in blood hypertension, diabetes, glucose intolerance, obesity and alcohol intake, compared to the Arab group. Smoking and high levels of seric cholesterol were similar in both groups, however, medium levels of seric cholesterol were lower in the Arab group. Family histories of cardiovascular disease were very rare in the latter mentioned group. These observations suggested a major predisposition to ischemic cardiopathy in the Spanish group.

Airway and lung parenchyma morphology during the respiratory cycle.

OBJECTIVE: Describe the morphological changes that take place in the lung parenchyma and in the airways during the respiratory cycle with a view to establishing a relationship between them. SUBJECTS: Adult Wistar rats. INTERVENTIONS: The lungs were fixed at seven different points in the respiratory cycle: Inflation, 10 and 20 cm. transpulmonary pressure, total lung capacity. Deflation, 20, 15, 10 and 0 cm transpulmonary pressure. MEASUREMENTS: The lungs were processed for morphometric study and bronchial and parenchymal variables, such as lung volume, number of alveoli, anatomic dead space, bronchial lumen surface and bronchial wall surface were quantified. The results were compared by analysis of variance (ANOVA) or the Kruskal-Wallis and Mann-Whitney's U tests. RESULTS: The lung volume, the number of alveoli and the anatomic dead space increased with the increase of the transpulmonary pressure and decreased with the decrease of it, the obtained values in deflation being higher than those in inflation (p<0.05). The bronchial lumen and the bronchial wall surfaces generally showed higher values in inflation than in deflation (p<0.05). CONCLUSIONS: The anatomic dead space was altered as a consequence of the variations in airway diameter and length. Lung parenchyma tension may have been of influence in the variations of the bronchial wall.

[Area mesencephalica on the raphe and its importance. (Stereometric reconstruction in cat) (author's trnsl)]. / Die Area mesencephalica an der Raphe und ihre Bedeutung. (Eine stereometrische Rekonstruktion bei der Katze).

The cat's mesencephalic raphe, caudally extended to the locus ceruleus and rostrally to the habenulo-interpedunculary area, was reconstructed with foamy-plastic plates in a stereotaxis ensemble of the brainstem. This reconstruction serves as an important reference to the topography and for interpreting the functional background of the stereotaxic lesions accumulated in the last 5 years. The alterations of the lung's alveolar interstitium after the nervous lesions, were classified in different groups of common evolution.