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.

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.

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.

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.

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.

La disfunción endotelial en la angiopatía diabética. El factor de crecimiento del endotelio vascular / Endothelial dysfunction in diabetic angiopathy. Vascular endothelial growth factor

La angiopatía es una complicación muy frecuente en los diabéticos. El daño endotelial multicausal origina tanto la micro como la macroangiopatía. La disfunción del endotelio sería la primera fase de la secuencia patogénica. Existe una serie de marcadores bioquímicos, morfológicos y funcionales que permiten su detección en estadios iniciales. Aunque en la retinopatía diabética ha sido ampliamente analizado el papel del factor de crecimiento del endotelio vascular (VEGF), parece que también puede tener una intervención en otras complicaciones vasculares, como son la nefropatía, la neuropatía y la macroangiopatía. Recientemente se han comenzado a ensayar tratamientos que modulan la acción de ese factor; sin embargo, las consecuencias que podrían derivarse sobre algunos territorios, como el coronario y el retiniano, pueden ser contrapuestas (AU)

N-acetylcysteine prevents cigarette smoke induced small airways alterations in rats.

This study investigated the effect of cigarette smoke exposure and the potential protection N-acetylcysteine (NAC) in rat lungs. Forty-eight rats were exposed to cigarette smoke (CS) for 10 weeks, without (CS group) or with (CS+NAC group) oral intake of NAC 200 mg x rat(-1) x day(-1), or to fresh air (Control). All rat lungs were assessed in terms of lung function, ventilation distribution (nitrogen, helium and sulphur hexafluoride phase III slopes), and morphometry (airway wall thickening of small, medium and large bronchi). The small bronchi, defined as the airways with an internal perimeter <1,000 microm showed significantly thicker airway walls in the CS than in the Control group. By contrast, no airway wall thickening was observed in the CS+NAC group with respect to Control. Except for decreased lung volumes and compliance in CS and CS+NAC groups, which were entirely attributable to smaller body weight gain, lung function was indistinguishable from Control. Phase III slopes were significantly increased only in the CS group. In conclusion, smoke-induced alterations in the rat lungs were reflected in wall thickening of the small bronchi and increased ventilation maldistribution. These smoke-induced morphometric and ventilation distribution alterations were prevented by N-acetylcysteine.

Architecture, elastic fiber, and collagen in the distal air portion of the lung of the 18-month-old rat.

BACKGROUND: The increase in the distal air spaces which takes place with age is the only sufficiently documented datum for differentiation between the senile and the adult lung. There are other pulmonary components which may be modified as the lung enters the phase of old age, but they have not as yet been sufficiently studied. The purpose of this study is to make a morphometric comparison between the wall thickness of the distal air spaces, elastic fiber, and collagen in lungs of rats of between 5 and 18 months of age. METHODS: The left lung of each rat was histologically processed for light microscopy. The sections were contrasted using methylene blue, resorcinfuchsin and Sirius red. Systematic randomized sampling was used for the selection of the histological fields studied. Morphometric variables were studied, and were systematized into three groups, namely: variables related with the alveolar architecture, variables which quantify elastic fiber, and those which quantify collagen. RESULTS: The old animals exhibited significant differences (p < 0.05) in the following variables: 1. In relation with the alveolar architecture, mean linear intercept, alveolar chord and wall thickness increased, whereas internal alveolar perimeter and tissue density decreased. 2. The relation elastic fiber density/lung tissue density increased. None of the variables which quantify collagen displayed significant differences. CONCLUSION: Our data lead us to consider that the lungs of the old animals displayed, not only an enlargement of the distal air spaces, but also a thickening of the alveolar wall and an increase in elastic fiber in relation to the rest of the lung tissue.

Methodological contributions for the morphometric study of the lung: approximation to the ideal sample size and quantification of collagen fiber.

BACKGROUND: A morphometric study of the rat lung was done to determine the importance, within the precision of a morphometric study, of the sample size in relation to the quality of the image and to propose a method for the quantification of lung collagen fiber. METHODS: Sixty Wistar rats, divided into two age groups consisting of adult and old rats, were used. The left lungs were studied and processed for light microscopy. Methylene blue, resorcin-fuchsin, and Sirius red stainings were performed. The variables were quantified automatically. In the sections stained with methylene blue, the variables alveolar chord, wall thickness, mean linear intercept index, tissue density, and internal alveolar perimeter were quantified, in two series, one with x40 magnification (panoramic image) and the other with x100 magnification. In the sections stained with resorcin-fuchsin, elastic fiber was quantified and the result related with that obtained for the variable tissue density. The results were compared statistically, and those obtained with different magnifications for single variables were related by using the correlation test; the misclassification indices were also calculated. In the sections stained with Sirius red, the surface that was birefringent to polarized light was quantified and related to the collagen fiber; the results were compared statistically. RESULTS: Concerning results obtained for single variables with different magnifications good, correlation indices were obtained (r > or = 0.62) for all but the wall thickness (r = 0.3). The results obtained for the panoramic images were the highest. The misclassification index was lower for the panoramic images. Significant differences (P < 0.5) were not found when comparing the mean birefringent surface in the two groups of animals. CONCLUSIONS: The results obtained lead us to consider that, despite the fact that the quality of the panoramic images is poorer, the results for these images are more accurate, possibly because a greater number of structures was analyzed. The measurement of the birefringent surfaces of the sections stained with Sirius red may be used in the study of lung collagen fiber.

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.

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.

[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.

Emphysema as a result of involuntary exposure to tobacco smoke: morphometrical study of the rat.

Several attempts have been made to describe the relation that exists between tobacco smoke and emphysema, through different experimental models of the active smoker. Despite the negative effects that involuntarily inhaled tobacco smoke can have on the lung, no experimental model of the passive smoker has been proposed. In this study, an experimental model of the involuntary smoker is described and the following hypothesis proposed: Passive exposure to tobacco smoke produces morphological alterations in the rat lung, which are compatible with emphysema. Emphysema will be considered to have been caused when enlargement of the distal airspaces of the lung and lung tissue destruction are demonstrated. Sixty Wistar rats were used, divided into two groups: a control group and a group that was passively exposed to tobacco smoke for a period of 3 months. A morphometrical study of the lung was performed using a computerized system. To demonstrate enlargement of the distal airspaces of the lung, the following variables were quantified: alveolar chord and mean linear intercept index (Lm); tissue loss was demonstrated by means of the quantification of the variables: tissue density, internal alveolar perimeter (IAP), and wall thickness (WT). The elastic fiber was also quantified. The animals that were exposed to tobacco smoke displayed the following significant alterations (p < .05): an increase of the alveolar chord and of the Lm, a decrease of the IAP, WT, and tissue density, and a loss of the elastic component of the lung. On the basis of these findings, it is concluded that the rats that were exposed in a passive way to tobacco smoke display morphological pulmonary alterations that are compatible with the definition of emphysema.

Changes occurring with increasing age in the rat lung: morphometrical study.

BACKGROUND: It was hypothesized that the evolution towards the senile lung is progressive, being initiated in the adult stage; and for this reason changes similar to those described in the senile lung can be detected in the lungs of middle-aged rats. To test the hypothesis, the following design was used. The lungs of two groups of rats, adult (mean age of 16 weeks) and middle-aged (mean age of 56 weeks) were morphometrically compared. METHODS: Thirty-one Wistar rats were used for the study; their lungs were processed histologically. The microscopic fields were analysed in a computer, and 20 variables were quantified. These were grouped into a) variables which describe the shape and size of the distal airspace, b) variables which describe the distal lung tissue, and c) variables which describe elastic fibers. The results were statistically compared: correlation tests were carried out, and the specificity, sensitivity, and misclassification indices were calculated. RESULTS: All the results of the variables which define the size of the airspaces were found to be significantly higher (P < 0.0001) in the middle-aged animals; the results obtained when the lung tissue was quantified directly from the histological section suggested a loss of tissue in the middle-aged animals. However, when these data were converted into absolute values, no loss was indicated in the total lung tissue. The values of the variables which describe the elastic fiber were found to have increased significantly (P < 0.0001) in the middle-aged animals. The misclassification index was found to be lower than 10% in six variables and between 10% and 20% in four. CONCLUSION: The low misclassification indices found lead us to consider that our morphometric method is ideal for distinguishing the lungs of the two groups of animals used. The results of the quantification of the variables show that the middle-aged animals exhibit simple enlargement of the distal airspaces, without tissue loss, which coincides with the current definition of the senile lung.

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)