High-Resolution Electron Microscopy of Semiconductor Heterostructures and Nanostructures

This chapter briefly describes the fundamentals of high-resolution electron microscopy techniques. In particular, the Peak Pairs approach for strain mapping with atomic column resolution, and a quantitative procedure to extract atomic column compositional information from Z-contrast high-resolution images are presented. It also reviews the structural, compositional, and strain results obtained by conventional and advanced transmission electron microscopy methods on a number of III–V semiconductor nanostructures and heterostructures

A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

Down syndrome, caused by an extra copy of chromosome 21, is associated with a greatly increased risk of early onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP), an Alzheimer risk factor, although the possession of extra copies of other chromosome 21 genes may also play a role. Further study of the mechanisms underlying the development of Alzheimer disease in Down syndrome could provide insights into the mechanisms that cause dementia in the general population

The human ventilatory response to acute hyperoxia during and after 8h of both isocapnic and poikilocapnic hypoxia

During 8 h of either isocapnic or poikilocapnic hypoxia, there may be a rise in ventilation (VE) that cannot be rapidly reversed with a return to higher PO2 (L. S. G. E. Howard and P. A. Robbins. J. Appl. Physiol. 78:1098-1107, 1995). To investigate this further, three protocols were compared: 1) 8-h isocapnic hypoxia [end-tidal PCO2 (PETCO2) held at prestudy value, end-tidal PO2 (PETO2) = 55 Torr], followed by 8-h isocapnic euoxia (PETO2 = 100 Torr); 2) 8-h poikilocapnic hypoxia followed by 8-h poikilocapnic euoxia; and 3) 16-h air-breathing control. Before and at intervals throughout each protocol, the VE response to eucapnic hyperoxia (PETCO2 held 1-2 Torr above prestudy value, PETO2 = 300 Torr) was determined. There was a significant rise in hyperoxic VE over 8 h during both forms of hypoxia (P < 0.05, analysis of variance) that persisted during the subsequent 8-h euoxic period (P < 0.05, analysis of variance). These results support the notion that an 8-h period of hypoxia increases subsequent hyperoxic VE, even if acid-base changes have been minimized through maintenance of isocapnia during the hypoxic period

Human ventilatory response to 8 h of euoxic hypercapnia.

Ventilation (VE) rises throughout 40 min of constant elevated end-tidal PCO2 without reaching steady state (S. Khamnei and P. A. Robbins. Respir. Physiol. 81: 117-134, 1990). The present study investigates 8 h of euoxic hypercapnia to determine whether VE reaches steady state within this time. Two protocols were employed: 1) 8-h euoxic hypercapnia (end-tidal PCO2 = 6.5 Torr above prestudy value, end-tidal PO2 = 100 Torr) followed by 8-h poikilocapnic euoxia; and 2) control, where the inspired gas was air. VE was measured over a 5-min period before the experiment and then hourly over a 16-h period. In the hypercapnia protocol, VE had not reached a steady state by the first hour (P < 0.001, analysis of variance), but there were no further significant differences in VE over hours 2-8 (analysis of variance). VE fell promptly on return to eucapnic conditions. We conclude that, whereas there is a component of the VE response to hypercapnia that is slow, there is no progressive rise in VE throughout the 8-h period

Changes in respiratory control during and after 48 hours of both isocapnic and poikilocapnic hypoxia in humans.

Ventilatory acclimatization to hypoxia is associated with an increase in ventilation under conditions of acute hyperoxia (VEhyperoxia) and an increase in acute hypoxic ventilatory response (AHVR). This study compares 48-h exposures to isocapnic hypoxia (protocol I) with 48-h exposures to poikilocapnic hypoxia (protocol P) in 10 subjects to assess the importance of hypocapnic alkalosis in generating the changes observed in ventilatory acclimatization to hypoxia. During both hypoxic exposures, end-tidal PO2 was maintained at 60 Torr, with end-tidal PCO2 held at the subject's prehypoxic level (protocol I) or uncontrolled (protocol P). VEhyperoxia and AHVR were assessed regularly throughout the exposures. VEhyperoxia (P &lt; 0.001, ANOVA) and AHVR (P &lt; 0.001) increased during the hypoxic exposures, with no significant differences between protocols I and P. The increase in VEhyperoxia was associated with an increase in slope of the ventilation-end-tidal PCO2 response (P &lt; 0.001) with no significant change in intercept. These results suggest that changes in respiratory control early in ventilatory acclimatization to hypoxia result from the effects of hypoxia per se and not the alkalosis normally accompanying hypoxia

Changes in cerebral blood flow during and after 48 h of both isocapnic and poikilocapnic hypoxia in humans.

During acclimatization to the hypoxia of altitude, the cerebral circulation is exposed to arterial hypoxia and hypocapnia, two stimuli with opposing influences on cerebral blood flow (CBF). In order to understand the resultant changes in CBF, this study examined the responses of CBF during a period of constant mild hypoxia both with and without concomitant regulation of arterial P(CO2). Nine subjects were each exposed to two protocols in a purpose-built chamber: (1) 48 h of isocapnic hypoxia (Protocol I), where end-tidal P(O2) (P(ET,O2)) was held at 60 Torr and end-tidal P(CO2) (P(ET,CO2)) at the subject's resting value prior to experimentation; and (2) 48 h of poikilocapnic hypoxia (Protocol P), where P(ET,O2) was held at 60 Torr and P(ET,CO2) was uncontrolled. Transcranial Doppler ultrasound was used to assess CBF. At 24 h intervals during and after the hypoxic exposure CBF was measured and the sensitivity of CBF to acute variations in P(O2) and P(CO2) was determined. During Protocol P, P(ET,CO2) decreased by 13% (P &lt; 0.001) and CBF decreased by 6% (P &lt; 0.05), whereas during Protocol I, P(ET,CO2) and CBF remained unchanged. The sensitivity of CBF to acute variations in P(O2) and P(CO2) increased by 103% (P &lt; 0.001) and 28% (P &lt; 0.01), respectively, over the 48 h period of hypoxia. These changes did not differ between protocols. In conclusion, CBF decreases during mild poikilocapnic hypoxia, indicating that there is a predominant effect on CBF of the associated arterial hypocapnia. This fall occurs despite increases in the sensitivity of CBF to acute variations in P(O2)/P(CO2) arising directly from the hypoxic exposure

Effects of 8h of eucapnic and poikilocapnic hypoxia on middle cerebral artery velocity and heart rate in humans.

This study examines the effects of prolonged hypoxia, with and without control of end-tidal CO2 partial pressure (PET,CO2), on the intensity-weighted mean velocity of blood flow in the middle cerebral artery (VIWM) and on heart rate (HR). Specifically, the time course of the responses, their reversibility with brief periods of hyperoxia and the recovery phase following prolonged hypoxia were all investigated. Twelve subjects were studied, of whom nine provided satisfactory data. A purpose-built chamber was used for the prolonged control of the end-tidal gases, and an end-tidal forcing system was used for generating the brief variations in end-tidal gases. Three 16 h protocols were employed: (1) 8 h eucapnic (average PET,CO2 = 39 mmHg) hypoxia (end-tidal O2 partial pressure, PET,O2 = 55 mmHg) followed by 8 h eucapnic euoxia (PET,O2 = 100 mmHg); (2) 8 h poikilocapnic (average PET,CO2 4 mmHg below eucapnia) hypoxia (PET,O2 = 55 mmHg) followed by 8 h poikilocapnic euoxia (PET,O2 = 100 mmHg); and (3) control (air inspired throughout). VIWM (using Doppler ultrasound) and HR were measured during brief exposures to hypoxic/euoxic and hyperoxic conditions with PET,CO2 held 1-2 mmHg above eucapnia, at 0, 20, 240 and 480 min in the first 8 h, and at the same times in the second 8 h. There were no significant trends in VIWM under hypoxic conditions for either hypoxic protocol (ANOVA) and no significant differences between the three protocols for VIWM in hyperoxia (ANOVA). In contrast to VIWM, there was a significant increase in HR over time during both hypoxic exposures (P &lt; 0.01, ANOVA). HR increased to a similar extent for the two types of hypoxia, and there was some suggestion that HR remained elevated after the relief of hypoxia. The results suggest that, with the level of hypoxia employed, progressive changes in HR occur, but that this level and duration of hypoxia has little sustained effect on VIWM