Detection-loophole-free test of quantum nonlocality, and applications.

We present a source of entangled photons that violates a Bell inequality free of the "fair-sampling" assumption, by over 7 standard deviations. This violation is the first reported experiment with photons to close the detection loophole, and we demonstrate enough "efficiency" overhead to eventually perform a fully loophole-free test of local realism. The entanglement quality is verified by maximally violating additional Bell tests, testing the upper limit of quantum correlations. Finally, we use the source to generate "device-independent" private quantum random numbers at rates over 4 orders of magnitude beyond previous experiments.

Legionella pneumophila: denizen of defenders.

Legionella pneumophila, the causative agent of legionellosis, is an intracellular parasite of human monocytic cells and neutrophils. The life cycle of Legionella within phagocytic cells is distinct from that of other bacterial pathogens. Adherence of L pneumophila to phagocytes is mediated by attachment of complement proteins to the Legionella cell surface, followed by binding to complement receptors of phagocytes. Opsonized Legionella also may enter phagocytes after engagement of the Fc receptors. Within the host cell, the parasites reside in a membrane-bound vacuole that does not fuse with lysosomes. Activation of mononuclear phagocytes by the cell-mediated immune system serves to limit intracellular bacterial growth. Polymorphonuclear leukocytes are better at killing L pneumophila than are macrophages. However, Legionella also can invade and parasitize granulocytes. Although significant progress has been made in understanding some aspects of the pathogenesis of legionellosis, we know very little about the mechanisms by which these facultative intracellular parasites avoid killing by host defense mechanisms. This is an important area for future research and should lead to a better understanding of host-parasite interactions.

Legionella pneumophila inhibits protein synthesis in Chinese hamster ovary cells.

Legionella pneumophila is a gram-negative facultative intracellular parasite that causes Legionnaires disease. To explore the interactions between L. pneumophila and host cells, we have developed a continuous cell line model of infection. We show that about 80% of Chinese hamster ovary (CHO) cells were associated with L. pneumophila after incubation for 3 h at a multiplicity of infection of 20 bacteria per cell. Within 3 to 4 h of incubation with L. pneumophila, protein synthesis of CHO cells was markedly inhibited, as shown by the reduction of incorporation of radiolabeled amino acids into proteins. L. pneumophila did not inhibit transport of amino acids or cause degradation of newly synthesized proteins in CHO cells. Cytochalasin D blocked internalization of L. pneumophila by CHO cells, yet CHO cell protein synthesis was inhibited. These results indicated that L. pneumophila could inhibit host protein synthesis from the cell exterior. L. pneumophila that had been killed with antibiotics prior to incubation with CHO cells still inhibited protein synthesis, indicating that the inhibition of CHO cell protein synthesis occurred in the absence of de novo protein synthesis by L. pneumophila.

Leukocyte function and chronic bronchitis.

Chronic bronchitis is a condition of mucous hypersecretion. It represents an interface between airway structures, cigarette smoke, and inflammatory cells. Chronic bronchitis is a late complication of smoking, typically occurring after 30 pack years. Stable patients have mucous hypersecretion and little evidence of acute inflammation. In contrast, during acute attacks of bronchitis, an intense accumulation of neutrophils occurs in the airways. Mechanisms of injury to airway structures include chemicals and reactive oxygen species within cigarette smoke, and secreted products of recruited neutrophils. Recent studies demonstrate that secreted products of polymorphonuclear leukocytes (PMNs) can cause secretory cell metaplasia and increase mucous production. Thus, the role of the PMN in chronic mucous hypersecretion appears to be a significant one. Cessation of cigarette smoking remains a most important aspect of caring for patients with chronic mucous hypersecretion.

Nicotine is chemotactic for neutrophils and enhances neutrophil responsiveness to chemotactic peptides.

Neutrophils contribute to chronic bronchitis and pulmonary emphysema associated with cigarette smoking. Nicotine was found to be chemotactic for human neutrophils but not monocytes, with a peak activity at approximately 31 micromolar. In lower concentrations (comparable to those in smokers' plasma), nicotine enhanced the response of neutrophils to two chemotactic peptides. In contrast to most other chemoattractants for neutrophils, however, nicotine did not affect degranulation or superoxide production. Nicotine thus may promote inflammation and consequent lung injury in smokers.

Amount of nicotine and carbon monoxide inhaled by smokers of low-tar, low-nicotine cigarettes.

In 76 smokers, correlations between plasma nicotine and alveolar carbon monoxide levels of the individual smoker and the nicotine and CO yields of his cigarette were very poor. In 24 smokers of low-nicotine, low-tar cigarettes, mean alveolar CO levels did not differ from those of smokers of regular cigarettes. Mean plasma nicotine levels were lower in smokers of low-nicotine cigarettes, but a wide overlap of individual values occurred. The implication that an individual shifting to ultra-low-tar cigarettes reduces risks of cardiopulmonary disease is unwarranted.

Deposition of sidestream cigarette smoke in the human respiratory tract.

Measurement of deposition of sidestream cigarette smoke in the human respiratory tract is important for assessing the health effects of sidestream cigarette smoke. We measured the deposition fraction of sidestream cigarette smoke in 5 normal adult male volunteers using sidestream smoke at a concentration similar to that encountered indoors with smokers present. The mean deposition was 11%. These data indicate that the deposition fraction of sidestream smoke is similar to other previously studied aerosols in the same size range and is much less than mainstream smoke.