The effect of high altitude on central blood pressure and arterial stiffness.

Central arterial systolic blood pressure (SBP) and arterial stiffness are known to be better predictors of adverse cardiovascular outcomes than brachial SBP. The effect of progressive high altitude (HA) on these parameters has not been examined. Ninety healthy adults were included. Central BP and the augmentation index (AI) were measured at the level of the brachial artery (Uscom BP+ device) at <200 m and at 3619, 4600 and 5140 m. The average age of the subjects (70% men) were 32.2±8.7 years. Compared with central arterial pressures, brachial SBP (+8.1±6.4 mm Hg; P<0.0001) and pulse pressure (+10.9±6.6 mm Hg; P<0.0001) were significantly higher and brachial diastolic BP was lower (-2.8±1.6 mm Hg; P<0.0001). Compared with <200 m, HA led to a significant increase in brachial and central SBP. Central SBP correlated with AI (r=0.50; 95% confidence interval (CI): 0.41-0.58; P<0.0001) and age (r=0.32; 95% CI: 21-0.41; P<0.001). AI positively correlated with age (r=0.39; P<0.001) and inversely with subject height (r=-0.22; P<0.0001), weight (r=-0.19; P=0.006) and heart rate (r=-0.49; P<0.0001). There was no relationship between acute mountain sickness scores (Lake Louis Scoring System (LLS)) and AI or central BP. The independent predictors of central SBP were male sex (coefficient, t=4.7; P<0.0001), age (t=3.6; P=0.004) and AI (t=7.5; P<0.0001; overall r2=0.40; P<0.0001). Subject height (t=2.4; P=0.02), age (7.4; P<0.0001) and heart rate (t=11.4; P<0.0001) were the only independent predictors of AI (overall r2=0.43; P<0.0001). Central BP and AI significantly increase at HA. This rise was influenced by subject-related factors and heart rate but not independently by altitude, LLS or SpO2.

Performance of silicon nanocrystal non-volatile memory devices under various programming mechanisms.

Non-volatile memory devices based on silicon nanocrystal synthesized with very low energy Si+ implantation are fabricated. Memory performance under various programming mechanisms including Fowler-Nordheim (FN), drain-bias channel-hot-electron (DCHE), and source-bias channel-hot-electron (SCHE) has been investigated. It is observed that the DCHE yields the largest memory window among the three programming mechanisms. The DCHE and SCHE have similar endurance characteristics, but the SCHE has a longer retention time than the DCHE. Both the DCHE and SCHE have a larger memory window, a better endurance and a longer retention time as compared to the FN. Explanations to the phenomena are given.

There are two mechanisms of achiasmate segregation in Drosophila females, one of which requires heterochromatic homology.

There are numerous examples of the regular segregation of achiasmate chromosomes at meiosis I in Drosophila melanogaster females. Classically, the choice of achiasmate segregational partners has been thought to be independent of homology, but rather made on the basis of availability or similarities in size and shape. To the contrary, we show here that heterochromatic homology plays a primary role in ensuring the proper segregation of achiasmate homologs. We observe that the heterochromatin of chromosome 4 functions as, or contains, a meiotic pairing site. We show that free duplications carrying the 4th chromosome pericentric heterochromatin induce high frequencies of 4th chromosome nondisjunction regardless of their size. Moreover, a duplication from which some of the 4th chromosome heterochromatin has been removed is unable to induce 4th chromosome nondisjunction. Similarly, in the absence of either euchromatic homology or a size similarity, duplications bearing the X chromosome heterochromatin also disrupt the segregation of two achiasmate X chromosome centromeres. Although heterochromatic regions are sufficient to conjoin nonexchange homologues, we confirm that the segregation of heterologous chromosomes is determined by size, shape, and availability. The meiotic mutation Axs differentiates between these two processes of achiasmate centromere coorientation by disrupting only the homology-dependent mechanism. Thus there are two different mechanisms by which achiasmate segregational partners are chosen. We propose that the absence of diplotene-diakinesis during female meiosis allows heterochromatic pairings to persist until prometaphase and thus to co-orient homologous centromeres. We also propose that heterologous disjunctions result from a separate and homology-independent process that likely occurs during prometaphase. The latter process, which may not require the physical association of segregational partners, is similar to those observed in many insects, in Saccharomyces cerevisiae and in C. elegans males. We also suggest that the physical basis of this process may reflect known properties of the Drosophila meiotic spindle.

The lethal(1)TW-6cs mutation of Drosophila melanogaster is a dominant antimorphic allele of nod and is associated with a single base change in the putative ATP-binding domain.

The l(1)TW-6cs mutation is a cold-sensitive recessive lethal mutation in Drosophila melanogaster, that affects both meiotic and mitotic chromosome segregation. We report the isolation of three revertants of this mutation. All three revert both the meiotic and mitotic effects as well as the cold sensitivity, demonstrating that all three phenotypes are due to a single lesion. We further show that these revertants fail to complement an amorphic allele of the nod (no distributive disjunction) locus, which encodes a kinesin-like protein. These experiments demonstrate that l(1)TW-6cs is an antimorphic allele of nod, and we rename it nodDTW. Sequencing of the nod locus on a nodDTW-bearing chromosome reveals a single base change in the putative ATP-binding region of the motor domain of nod. Recessive, loss-of-function mutations at the nod locus specifically disrupt the segregation of nonexchange chromosomes in female meiosis. We demonstrate that, at 23.5 degrees, the meiotic defects in nodDTW/+ females are similar to those observed in nod/nod females; that is, the segregation of nonexchange chromosomes is abnormal. However, in nodDTW/nodDTW females, or in nodDTW/+ females at 18 degrees, we observe a more severe meiotic defect that apparently affects the segregation of both exchange and nonexchange chromosomes. In addition, nodDTW homozygotes and hemizygous males have previously been shown to exhibit mitotic defects including somatic chromosome breakage and loss. We propose that the defective protein encoded by the nodDTW allele interferes with proper chromosome movement during both meiosis and mitosis, perhaps by binding irreversibly to microtubules.

Influence of beta-lactamase inhibitors on the potency of their companion drug with organisms possessing class I enzymes.

The ability of beta-lactamase inhibitors to induce class I beta-lactamases in certain organisms in vitro suggests a potential for antagonism in vivo. Therefore, a study was designed to assess the ability of sulbactam and clavulanate to induce beta-lactamases in two strains each of Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, and Pseudomonas aeruginosa both in vitro and in vivo. Induction in vitro was observed only with S. marcescens and P. aeruginosa and generally only when inhibitor concentrations greater than 2 micrograms/ml were examined. A mouse model of lethal infection, designed to detect in vivo antagonism arising from beta-lactamase induction, was used to determine what effect sulbactam and clavulanate would have on the 50% protective doses (PD50s) of cefoperazone and ticarcillin. Antagonism (a significant increase in the PD50) was observed in only 4 of 32 tests. Three of these involved antagonism of cefoperazone by clavulanate, and one involved antagonism of cefoperazone by sulbactam. In 6 of 32 tests, enhancement of efficacy (a significant decrease in PD50) was observed. In four of these, sulbactam enhanced cefoperazone; in one, sulbactam enhanced ticarcillin; and in one, clavulanate enhanced ticarcillin. Four of the six cases of enhancement occurred when the beta-lactamase inhibitor was given at the time of challenge. None of these positive or negative in vivo effects were predicted by in vitro tests. These data suggest that beta-lactamase inhibitors can influence the in vivo potency of their companion drug in both a beneficial and detrimental fashion against organisms with class I beta-lactamases and that these effects cannot be predicted from in vitro assays.

False-positive gram-stained smears of sterile body fluids due to contamination of laboratory deionized water.

Bacterial contamination of staining reagents led to false-positive smears from clinical samples. Piped deionized water used to make up the staining reagents was found to be the source of contamination. The closed loop system supplying the deionized water was decontaminated with hydrogen peroxide and upgraded by addition of a reverse osmosis unit and bacterial filter. No subsequent contamination has been demonstrated.

Bordetella bronchiseptica and toxigenic type D Pasteurella multocida as agents of severe atrophic rhinitis of swine.

Bordetella bronchiseptica and toxigenic type-D Pasteurella multocida were cultured from pigs in each of five herds diagnosed as having severe atrophic rhinitis (AR). B. bronchiseptica alone, P. multocida alone, or both organisms isolated from four herds were inoculated intranasally into 1-week-old gnotobiotic pigs which were necropsied 4 weeks post-inoculation (PI). Nasal turbinate atrophy in B. bronchiseptica-inoculated pigs was moderate to severe, while P. multocida-inoculated pigs had slight to severe atrophy. Pigs inoculated with both organisms had moderate to complete turbinate atrophy. P. multocida was reisolated at necropsy from all pigs receiving the organism except those having no turbinate damage. B. bronchiseptica and P. multocida from a fifth herd were simultaneously inoculated into six naturally farrowed 6-day-old SPF pigs. Necropsy performed 4 weeks PI revealed severe to complete turbinate atrophy. Nasal turbinates were normal for control pigs in both experiments.