Dawning of the N=32 Shell Closure Seen through Precision Mass Measurements of Neutron-Rich Titanium Isotopes.

A precision mass investigation of the neutron-rich titanium isotopes ^{51-55}Ti was performed at TRIUMF's Ion Trap for Atomic and Nuclear science (TITAN). The range of the measurements covers the N=32 shell closure, and the overall uncertainties of the ^{52-55}Ti mass values were significantly reduced. Our results conclusively establish the existence of the weak shell effect at N=32, narrowing down the abrupt onset of this shell closure. Our data were compared with state-of-the-art ab initio shell model calculations which, despite very successfully describing where the N=32 shell gap is strong, overpredict its strength and extent in titanium and heavier isotones. These measurements also represent the first scientific results of TITAN using the newly commissioned multiple-reflection time-of-flight mass spectrometer, substantiated by independent measurements from TITAN's Penning trap mass spectrometer.

Zwitterionic and anionic multinuclear pentacoordinate silicon(IV) complexes with bridging (R,R)-tartrato(4-) ligands and SiO5 skeletons: synthesis and reactivity in aqueous solution.

Two nutrients in one molecule: A zwitterionic λ(5)Si,λ(5)Si'-disilicate (1) was synthesized and characterized. It contains ligands that exclusively derive from natural products ((R,R)-tartaric acid, choline). Hydrolysis of 1 yields 2, which shows a remarkable kinetic stability in water. Upon dissolution of 1 and 2 in water, the nutrients choline and orthosilicic acid are formed by hydrolysis.

Clean Indoor Air Acts reduce the burden of adverse cardiovascular outcomes.

OBJECTIVES: Second-hand smoke is associated with an increased risk of adverse health outcomes, such as acute myocardial infarction (AMI) and coronary heart disease (CHD). At present, 38 US states/territories have enacted Clean Indoor Air Acts (CIAAs). The purpose of the current study was to compare the prevalence of self-reported health outcomes on a state/territory-wide level 1 year prior to CIAA implementation and at least 1 year after CIAA implementation for each respective state/territory. STUDY DESIGN: Pre-test, post-test study. METHODS: Seventeen states/territories with pre- and post-CIAA data were included in the current study. All data (AMI, CHD/angina, former and current smoker rates) were collected from the Behavioral Risk Factor Surveillance System (BRFSS) in the year prior to each state/territory's respective CIAA implementation (baseline) and 2009 (most recent year with BRFSS data). RESULTS: Between baseline and 2009, 10 states/territories (58.8%) had a significant decrease in the prevalence of CHD/angina or AMI, 11 states/territories (64.7%) had a significant decrease in the prevalence of current smokers, and three states/territories (17.7%) had a significant decrease in the prevalence of both current and former smokers. Six states/territories (35.3%) had a significant increase in the prevalence of former smokers. CONCLUSIONS: State/territory-wide CIAAs are beneficial in reducing adverse cardiovascular health outcomes in the short term. The prevalence of AMI, CHD/angina, and former and current smokers decreased significantly following CIAA implementation. The current study adds further support for the passage and implementation of CIAAs on a state/territory-wide level. However, further studies need to be conducted to assess the long-term outcomes of CIAAs.

Pulmonary alveolar macrophage. Defender against bacterial infection of the lung.

The rate of ingestion of inhaled bacteria by pulmonary alveolar macrophages is an important determinant of host defense. This parameter was investigated by infecting rats with finely dispersed aerosols bearing Staphylococcus aureus in high concentrations (about 10(s) bacteria/ft(3)/min). These aerosols deposited more than 10(6) bacteria/murine lung. At 0, 2(1/2), and 5 h after infection, bacterial clearance rates were measured in the left lung, and the intracellular or extracellular location of 100 bacteria was determined histologically in the right lung (perfused in situ). The clearance rates at 2(1/2) and 5 h were 44.5% and 76.9%, respectively. The percentages of intracellular bacteria were: 0 h, 54.8%; 2(1/2) h, 87.1%: 5 h, 91.9%. When rats were exposed for 4 h to 2.5 ppm of ozone (O(3)), bacterial clearance did not occur - 15.3%, although 78.7% of the bacteria were intracellular. Clumps of more than 10 bacteria-usually intracellular-were also present. These experiments demonstrate that phagocytic ingestion is an exceedingly rapid process, that in this experimental model the inactivation of inhaled staphylococci results almost entirely from phagocytosis, and that ozone-induced reductions in bacterial clearance are due to severe impairment of intrapulmonary killing mechanisms and minor impairment of bacterial ingestion.

Polymorphonuclear leucocyte motility in patients with severe burns.

Chemotaxis, chemokinesis and cellular orientation were measured for unstimulated and 10(-7) n-formyl methionyl leucyl phenylalanine (F-met-leu-phe) stimulated polymorphonuclear leucocytes (PMNS) of nine patients with recent 10-80 per cent burns using a computer-assisted image analysis technique. The technique records PMN movement, as viewed with a phase-contrast microscope on videotapes, and then uses computer programs to calculate the speed and direction of up to 50 PMNS over a 5-min period. Orientation was determined visually. Cellular adherence was also measured by attachment methods. PMNS from burn patients were slower (av. speed 16.8 microns/min), responded less well to F-met-leu-phe (av. speed 20.9 microns/min, av. McCutcheon index 0.32), were less often oriented towards the chemoattractant (av. 39 per cent) and were more adherent (av. 50 per cent) than control cells (av. speed 21.8 microns/min; av. speed F-met-leu-phe 32.2 microns/min; McCutcheon index 0.61; oriented 59 per cent adherent; 16 per cent). Thus PMNS from burn patients orient less well, are significantly slower and have less directionality in response to a chemoattractant, and are more adherent suggesting activation.

Effect of ferrous sulfate aerosols and nitrogen dioxide on murine pulmonary defense.

A murine infectivity model was used to test the effect of exposure to atmospheres containing 290 +/- 50 microgram/m3 of respirable sized ferrous sulfate (FeSO4) particles (0.4 micron mass median aerodynamic diameter) and 1.0 ppm nitrogen dioxide (NO2) prior to infection with aerosols of Staphylococcus aureus or group C streptococci. Exposure to these combined pollutants for 24 or 48 hr did not impair pulmonary inactivation of S. aureus. Exposure to FeSO4 or NO2 for 48 hr, or to both pollutants for 24 or 48 hr, resulted in significant decreases in inactivation of inhaled group C streptococci. Mortality studies following pollutant exposure demonstrated earlier, but not an increased number of deaths. These studies demonstrate the importance of the test organism in assessing air quality standards with the infectivity model and enhanced toxicity and prolongation of exposure to relatively low levels of submicron-size particles of FeSO4 and NO2.

Effect of near ambient exposures to sulfur dioxide and ferrous sulfate particles on murine pulmonary defense mechanisms.

An infectivity model was used to test the safety margins for presently established air quality standards for sulfur dioxide and sulfate particles. Mice and rats were exposed to atmospheres of sulfur dioxide and mono-disperse ferrous sulfate particles from 3 to 6 times the standard for 17 hr prior to, or 4 hr after infection with aerosols of Staphylococcus aureus or Group C Streptococci. Exposure to these concentrations of pollutants did not impair the rodents' ability to ingest and inactivate the minimally virulent Straphylococcus or enhance the virulence of the Group C Streptococci. Insofar as these results can be extrapolated to man, the present air quality standards for sulfur dioxide and sulfate particles are protective in regard to respiratory bacterial infection.

Novel silicon-containing analogues of the retinoid agonist bexarotene: syntheses and biological effects on human pluripotent stem cells.

Twofold sila-substitution (C/Si exchange) of the clinically used RXR-selective retinoid agonist bexarotene leads to disila-bexarotene, which displays pharmacological potency similar to that of the parent carbon compound, as shown in a HeLa-cell-based RXR assay. Formal exchange of the SiCH2CH2 Si group in disila-bexarotene with a SiCH2Si or SiOSi moiety leads to the disila-bexarotene analogues 8 and 9. The silicon compounds 8 and 9 were synthesized in multistep syntheses, starting from HC≡C(CH3)2SiCH2Si(CH3)2C≡CH and HC≡C(CH3)2SiOSi(CH3)2C≡CH, respectively. The key step in the syntheses of 8 and 9 is a cobalt-catalyzed [2+2+2] cycloaddition reaction that affords the 1,3-disilaindane and 2-oxa-1,3-disilaindane skeletons. Disila-bexarotene and its analogues 8 and 9 were studied for their biological effects relative to all-trans retinoic acid in cultured human pluripotent stem cells. The parent carbon compound bexarotene was included in some of these biological studies. Although the silicon-containing bexarotene analogues disila-bexarotene, 8, and 9 appear not to regulate the differentiation of TERA2.cl.SP12 stem cells, preliminary evidence indicates that these compounds may possess enhanced functions over the parent compound bexarotene, such as induction and regulation of cell death and cell numbers. The biological data obtained indicate that bexarotene, contrary to the silicon-containing analogues disila-bexarotene, 8, and 9, may partially act to induce cell differentiation.

Silicon analogues of the RXR-selective retinoid agonist SR11237 (BMS649): chemistry and biology.

C/Si switch: Twofold sila-substitution (C/Si exchange) in the RXR-selective retinoids 4 a (SR11237) and 5 a leads to 4 b (disila-SR11237) and 5 b, respectively. Chemistry and biology of the C/Si pairs are reported.SR11237 (BMS649, 4 a) is a pan-RXR-selective retinoid agonist. Its silicon analogue, disila-SR11237 (4 b; twofold C/Si exchange), was prepared in a multistep synthesis by starting from 1,2-bis(ethynyldimethylsilyl)ethane. In addition, the related C/Si analogues 5 a and 5 b, with an indane (disila-indane) instead of a tetraline (disila-tetraline) skeleton, were synthesized. The C/Si pairs 4 a/4 b and 5 a/5 b were studied for their interaction with retinoid receptors and were demonstrated to be highly potent RXR-selective ("rexinoid") agonists. Interestingly, twofold C/Si exchange in the indane moiety of 5 a resulted in a 10-fold increase in biological activity of the corresponding silicon-containing rexinoid 5 b, possibly resulting from an increased receptor affinity or a divergent allosteric effect on co-regulator-binding surfaces. The crystal structures of the ternary complexes formed by 5 a and 5 b, respectively, with the ligand-binding domain of hRXRalpha and a peptide of the co-activator TIF2/GRIP1 revealed additional interactions of the disila analogue 5 b with the H7 and H11 residues, supporting the first option of increased binding affinity. This is the first demonstration of an increase in binding affinity of a ligand to a nuclear receptor by C/Si replacement, thereby adding this C/Si switch strategy to the repertoire of nuclear receptor ligand design.

Cellular acid phosphatase activity: correlation of cytochemical and biochemical measurements.

Methods for comparing results of cellular acid phosphatase activities obtained by quantitative cytospectrophotometry with those obtained by biochemical analysis are needed to express the cytospectrophotometric data in biochemical units. Since naturally occurring cells have differing amounts of acid phosphatase, enzyme activity was measured cytochemically and biochemically in polymorphonuclear leukocytes and peritoneal and alveolar macrophages from male rats to determine if these measurements permitted construction of a line correlating the two parameters. Cellular acid phosphatase activity, as measured cytospectrophotometrically and biochemically, increased proportionately with polymorphonuclear leukocytes having the lowest activities and alveolar macrophages the highest. These values when subjected to linear regression analysis fixed a line with a correlation coefficient of 0.95 demonstrating that cytochemical and biochemical activities of acid phosphatase activity can be correlated using naturally occurring cells.

Group B streptococcal lung infection in neonatal rabbits.

The interaction of alveolar macrophages (AMs) and group B streptococci (GBS) was investigated in 1 and 2-day-old rabbits following infection in an exposure chamber containing 10(7) streptococci per cubic foot of air. The % of streptococci within AMs was similar at 0 and 4 h (36 and 65%) after infection for the two groups of rabbits. Twenty-four h after infection, the 2-day-old rabbits had a significantly higher % of ingested GBS (86 versus 68%). Sixty % of inspired GBS were inactivated by the older rabbits within 4 h after infection. This clearance persisted in the younger rabbits until 48 h (mean negative clearance of -17, -276, and -79% at 4, 24, and 48 h) before their numbers were reduced by inflammation. Sixty of 78 1-day-old rabbits had inflammatory responses between 24 and 72 h versus only 5 of 50 older rabbits. At 24 h after infection, AMs of 1-day-old rabbits contained significantly increased numbers of intracellular GBS microcolonies (17/20) than did AMs from 2-day-old rabbits (5/19). These observations suggest that the enhanced susceptibility to GBS infection in the immediate postnatal period is caused at least in part by ineffective intracellular killing by AMs.

Effect of 0.64 ppm ozone on alveolar macrophage lysozyme levels in rats with chronic pulmonary bacterial infection.

A rat model of chronic pulmonary infection (CPI) initiated by Pseudomonas aeruginosa embedded in agar beads was used to test the effect of ozone on lysosomal enzyme levels in alveolar macrophages (AM). CPI was induced by intratracheal instillation of a 0.1-ml suspension of infected beads into the left lung. Ten days after infection half the rats were exposed to atmospheres of air and half to 0.64 ppm ozone for 4 weeks. Enzyme levels were measured using a scanning cytospectrophotometer linked to PDP/11 computer. Measurement of lysozyme in individual rat AM in situ showed a significant decrease in cell size and enzyme content in ozone-exposed uninfected animals. Cell size and enzyme content of ozone-exposed animals with CPI were further reduced, suggesting a synergistic effect between ozone exposure and chronic infection.

Neonatal lung defense mechanisms: a study of the alveolar macrophage system in neonatal rabbits.

Abnormal function of the alveolar macrophage system may explain the enhanced susceptibility to pulmonary infection in human neonates. This hypothesis was investigated by infecting 1- to 14-day-old rabbits with aerosols of Staphylococcus aureus and then measuring in situ rates of bacterial ingestion, inactivation, and destruction in the lapine lung. The inhaled staphylococci were killed within the lungs of 1-day-old rabbits at a significantly slower rate than that for 7- and 14-day-old rabbits (P less than 0.05). Much of this decrease was due to diminished rates of bacterial ingestion by alveolar macrophages of younger animals. Staphylococci were also killed and destroyed less rapidly within these macrophages, but these differences could not be tested for significance.

Effect of protein A on the antistaphylococcal defence mechanisms of the murine lung.

The importance of IgG attached to protein A in the initial reaction of inspired Staphylococcus aureus and alveolar macrophages was studied by infecting unimmunized mice with aerosols of S. aureus strains 566 and Wood 46 with high and low protein A content. At 2, 4, and 8 hr after infection, the presence of IgG attached to S. aureus and rates of staphylococcal ingestion and killing by macrophages were determined. IgG was detected by staining of sections of the right lung with fluorescein-labeled goat antibody to mouse IgG. For S. aureus strain 566, 25%--40% of the total number of bacteria, as determined in equivalently sized subjacent sections stained by the Brown and Brenn tissue gram stain, contained attached IgG. A few S. aureus strain Wood 46 were surrounded by dimly fluorescing complexes. Since rates of bacterial ingestion and killing were similar for both strains in this in vivo model of infection, IgG binding to protein A does not affect the bactericidal capacity of alveolar macrophages.

Lung response to congenitally athymic (nude), heterozygous, and Swiss Webster mice to aerogenic and intranasal infection by Nocardia asteroides.

Congenitally athymic (nude, Nu/Nu), heterozygous (Nu/+), and Swiss Webster mice were exposed to virulent Nocardia asteroides GUH-2 inhaled from aerosols or administered intranasally. Clearance of the bacteria from the lungs was determined at 6 h and 1, 2, 3 and 7 days after infection. N. asteroides aspirated into the lungs from intranasal administration were killed less rapidly and induced more severe pulmonary infections than did comparable numbers of organisms inhaled from aerosols. Bacterial clearance and histological data indicated that nude mice were significantly more susceptible to nocardial infection than were heterozygous littermates or Swiss Webster mice. From these data we conclude that: (i) pulmonary defenses cope less well with intranasally administered N. asteroides than with aerosolized organisms, (ii) alveolar macrophages alone appear not to be an efficient barrier to nocardial infections, and (iii) T cells are important to pulmonary clearance and prevention of dissemination of N. asteroides from the lung.

Murine pulmonary alveolar macrophages: rates of bacterial ingestion, inactivation, and destruction.

The component processes of phagocytosis (ingestion, inactivation, and destruction of bacteria) were studied in mice by histological and microbiological techniques after aerosol infection with Staphylococcus aureus. Rates of bacterial ingestion and inactivation were (respectively): 0 hr, 37.7% and 0; 1 hr, 64.5% and 45.8%; 2 hr, 75.9% and 67.9%; 4 hr, 82.4% and 84.1%; and 8 hr, 90.7% and 94.8%. Bacterial destruction began 2-4 hr after aerosol infection and affected 80% of the bacteria by 8 hr. Comparison of these processes indicated that bacterial ingestion occurred before inactivation and was 76% complete at 2 hr. Inactivation resulted in death of 84% of the bacteria at 4 hr, and 80% of the bacteria were at least partially destroyed by 8 hr. The mechanism of X-irradiation-induced depression of pulmonary bacterial inactivation was studied in syngeneic mice protected from lethal effects of X-irradiation by chest and pelvic shields or by transplantation of 2 times 10(6) bone marrow cells. Impairments in bacterial inactivation resulted from diminished ingestion of bacteria by macrophages.

Effect of influenza viral infection on the ingestion and killing of bacteria by alveolar macrophages.

In experimental animals, influenza prediposes the lung to superinfection by reducing the antibacterial efficiency of the alveolar macrophage system. Because such defects may represent abnormalities in ingestion or inactivation of inhaled bacteria, these subcomponents of phagocytosis were tested in mice infected 5 days previously with influenza A virus (NWS or WSN). The mice were exposed to aerosols of Staphylococcus epidermidis and then the rates of bacterial inactivation and percentages of intracellularly located staphylococci were measured. Rates of bacterial inactivation were determined for the left lung by pour-plate enumeration methods. The percentage of ingested bacteria was determined in the in situ perfused right lung by histologically determining the intra- or extracellular location of 100 or more staphylococci. Rates of inactivation of S. epidermidis at 4 hours after bacterial challenge were: control, 90.1 per cent; WSN, 73.0 per cent; NWS, 68.6 per cent, P less than 0.01. The percentage of intracellular staphylococci at 4 hours were: control, 90.9 per cent; WSN, 69.9 per cent; and NWS, 73.8 per cent, P less than 0.01. Microcolonies of proliferating staphylococci were also observed within macrophages of mice infected with each strain of influenza. These experiments demonstrated that in this experimental model, influenzal infection impairs the inactivation of inhaled bacteria by retarding the ingestion of bacteria and by allowing bacteria to proliferate within macrophages.

A quantitative method for the analysis of cell shape and locomotion.

A rapid, semiautomated system to quantitate and analyze leukocyte shape and locomotion was developed. Video images of moving leukocytes were obtained using a Vidicon camera mounted on a Nikon phase microscope. The video signal was either inputted directly, or indirectly via a video cassette recorder, to a Datacube video analog-digital, digital-analog converter. A Digital Equipment Corporation LSI 11/23 computer using the RT-11/TSX-Plus operating system and computer programs written in FORTRAN and MARCO assembly language permitted image segmentation, image display, and calculation of position, speed, direction of movement and orientation of each leukocyte at 10 s intervals. These data were stored on a winchester disk for subsequent evaluation of the leukocyte orientation, speed and direction of movement using statistical and graphical methods. The reproducibility of measurements made with the video system was tested by comparison with manual measurements; a correlation coefficient of 0.998 was obtained for the two methods. Rates of chemokinesis were then determined for unstimulated and chemokinetically stimulated polymorphonuclear leukocytes (PMNs) and found to average 12.8 micron/min and 18.1 micron/min, respectively. The high speed, ease of data analysis, and potential for multiparameter evaluation makes this system useful for directly evaluating leukocyte locomotion.

A computer-assisted image-analysis system for analyzing polymorphonuclear leukocyte chemotaxis in patients with diabetes mellitus.

A computer-assisted image-analysis system that precisely tracks the cell movements of up to 50 polymorphonuclear leukocytes (PMNLs) was developed and used to quantitatively measure cellular chemokinesis and chemotaxis in normal individuals and in diabetic patients with hyperglycemia. The PMNLs were tested in Zigmond chambers with or without a gradient of 10(-7) M n-formylmethionylleucylphenylalanine (f-Met-Leu-Phe). Cellular movement was recorded on videotape by using a videocamera mounted on the microscope. The videotapes were analyzed by computer programs to calculate the speed and direction of each PMNL at 10-sec intervals. Average rates of chemokinesis were 19.6 microns/min without and 25.3 microns/min with f-Met-Leu-Phe. McCutcheon indices, which measure chemotaxis, were 0.01 without and 0.48 with f-Met-Leu-Phe. Similar values were observed in diabetic patients after fasting (average glucose, 217 mg/100 ml) and 2 hr after glucose challenge (average glucose, 309 mg/100 ml). These values demonstrate that PMNLs from diabetic patients with hyperglycemia move at normal rates and respond appropriately to f-Met-Leu-Phe.