Cytopathogenesis of Sendai virus in well-differentiated primary pediatric bronchial epithelial cells

Sendai virus (SeV) is a murine respiratory virus of considerable interest as a gene therapy or vaccine vector, as it is considered nonpathogenic in humans. However, little is known about its interaction with the human respiratory tract. To address this, we developed a model of respiratory virus infection based on well-differentiated primary pediatric bronchial epithelial cells (WD-PBECs). These physiologically authentic cultures are comprised of polarized pseudostratified multilayered epithelium containing ciliated, goblet, and basal cells and intact tight junctions. To facilitate our studies, we rescued a replication-competent recombinant SeV expressing enhanced green fluorescent protein (rSeV/eGFP). rSeV/eGFP infected WD-PBECs efficiently and progressively and was restricted to ciliated and nonciliated cells, not goblet cells, on the apical surface. Considerable cytopathology was evident in the rSeV/eGFP-infected cultures postinfection. This manifested itself by ciliostasis, cell sloughing, apoptosis, and extensive degeneration of WD-PBEC cultures. Syncytia were also evident, along with significant basolateral secretion of proinflammatory chemokines, including IP-10, RANTES, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), interleukin 6 (IL-6), and IL-8. Such deleterious responses are difficult to reconcile with a lack of pathogenesis in humans and suggest that caution may be required in exploiting replication-competent SeV as a vaccine vector. Alternatively, such robust responses might constitute appropriate normal host responses to viral infection and be a prerequisite for the induction of efficient immune responses.

Low-energy excitations of a boson pair in a double-well trap

The states of a boson pair in a one-dimensional double-well potential are investigated. Properties of the ground and lowest excited states of this system are studied, including the two-particle wave function, momentum pair distribution, and entanglement. The effects of varying both the barrier height and the effective interaction strength are investigated.

Matching Well-Being to Merit:The Example of Punishment

In this paper, I explore our common-sense thinking about the relation between moral value, moral merit, and well-being. Starting from Ross’s observation that welfarist axiologies ignore our intuitions about desert, I focus on axiologies that take moral merit and well-being to be independent determinants of value. I distinguish three ways in which these axiologies can be formulated, and I then consider their application to the issue of punishment. The objection that they recommend penalties in circumstances in which intuitively we would judge them to be unjustified is examined, and I suggest that it can be met by incorporating temporal information into the way in which value, well-being and moral merit are linked.

The effect of animals on human health and well-being

Substantial sums of money are invested annually in preventative medicine and therapeutic treatment for people with a wide range of physical and psychological health problems, sometimes to no avail. There is now mounting evidence to suggest that companion animals, such as dogs and cats, can enhance the health of their human owners and may thus contribute significantly to the health expenditure of our country. This paper explores the evidence that pets can contribute to human health and well-being. The article initially concentrates on the value of animals for short- and long-term physical health, before exploring the relationship between animals and psychological health, focusing on the ability of dogs, cats, and other species to aid the disabled and serve as a "therapist" to those in institutional settings. The paper also discusses the evidence for the ability of dogs to facilitate the diagnosis and treatment of specific chronic diseases, notably cancer, epilepsy, and diabetes. Mechanisms underlying the ability of animals to promote human health are discussed within a theoretical framework. Whereas the evidence for a direct causal association between human well-being and companion animals is not conclusive, the literature reviewed is largely supportive of the widely held, and long-standing, belief that "pets are good for us." © 2009 The Society for the Psychological Study of Social Issues.

The Implications of Bach's Introduction of New Fugal Techniques and Procedures in the Well-Tempered Clavier Book Two

Among the fugues of the WTC II, there are some fugal techniques and procedures that were not explored in the first book. Here, the ‘fugal techniques’ include parallel entries (as used in the fugues in D-sharp minor, G minor and B-flat minor) and double counterpoint at the tenth or twelfth as well as fifteenth (as used in the fugues in G minor and B major). The ‘fugal procedures’, on the other hand, refer to meticulously planned multi-exposition architecture (as seen in the fugues in F-sharp minor exploiting two subsidiary subjects, and B-flat minor exploiting inversion and stretto) and a form in which the appearance of the subsidiary subject is gradually predicted in the fugal discourse (viz. C-sharp minor, G-sharp minor and B major). All these new ideas helped Bach to write more dramatic, more profound fugues for WTC II. The paper will consider how Bach came to acquire the new techniques and to use them in such ways, and what motivated him to adopt these new compositional approaches. Do they offer any clues for our better understanding of why Bach compiled the WTC II?