Oncolytic herpes viruses, chemotherapeutics, and other cancer drugs

Oncolytic viruses are emerging as a potential new way of treating cancers. They are selectively replication-competent viruses that propagate only in actively dividing tumor cells but not in normal cells and, as a result, destroy the tumor cells by consequence of lytic infection. At least six different oncolytic herpes simplex viruses (oHSVs) have undergone clinical trials worldwide to date, and they have demonstrated an excellent safety profile and intimations of efficacy. The first pivotal Phase III trial with an oHSV, talimogene laherparepvec (T-Vec [OncoVex<sup>GM-CSF</sup>]), is almost complete, with extremely positive early results reported. Intuitively, therapeutically beneficial interactions between oHSV and chemotherapeutic and targeted therapeutic drugs would be limited as the virus requires actively dividing cells for maximum replication efficiency and most anticancer agents are cytotoxic or cytostatic. However, combinations of such agents display a range of responses, with antagonistic, additive, or, perhaps most surprisingly, synergistic enhancement of antitumor activity. When synergistic interactions in cancer cell killing are observed, chemotherapy dose reductions that achieve the same overall efficacy may be possible, resulting in a valuable reduction of adverse side effects. Therefore, the combination of an oHSV with “standard-of-care” drugs makes a logical and reasonable approach to improved therapy, and the addition of a targeted oncolytic therapy with “standard-of-care” drugs merits further investigation, both preclinically and in the clinic. Numerous publications report such studies of oncolytic HSV in combination with other drugs, and we review their findings here. Viral interactions with cellular hosts are complex and frequently involve intracellular signaling networks, thus creating diverse opportunities for synergistic or additive combinations with many anticancer drugs. We discuss potential mechanisms that may lead to synergistic interactions

Conditions Necessary for Plants to Grow Well

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Modeling Course-Based Undergraduate Research Experiences: An Agenda for Future Research and Evaluation

Course-based undergraduate research experiences (CUREs) are being championed as scalable ways of involving undergraduates in science research. Studies of CUREs have shown that participating students achieve many of the same outcomes as students who complete research internships. However, CUREs vary widely in their design and implementation, and aspects of CUREs that are necessary and sufficient to achieve desired student outcomes have not been elucidated. To guide future research aimed at understanding the causal mechanisms underlying CURE efficacy, we used a systems approach to generate pathway models representing hypotheses of how CURE outcomes are achieved. We started by reviewing studies of CUREs and research internships to generate a comprehensive set of outcomes of research experiences, determining the level of evidence supporting each outcome. We then used this body of research and drew from learning theory to hypothesize connections between what students do during CUREs and the outcomes that have the best empirical support. We offer these models as hypotheses for the CURE community to test, revise, elaborate, or refute. We also cite instruments that are ready to use in CURE assessment and note gaps for which instruments need to be developed.Howard Hughes Medical InstituteScience and Mathematics Educatio

Environmental Impact on the Southeast Limb of the Cygnus Loop

We analyze observations from the Chandra X-ray Observatory of the southeast knot of the Cygnus Loop supernova remnant. In this region, the blast wave propagates through an inhomogeneous environment. Extrinsic differences and subsequent multiple projections along the line of sight rather than intrinsic shock variations, such as fluid instabilities, account for the apparent complexity of the images. Interactions between the supernova blast wave and density enhancements of a large interstellar cloud can produce the morphological and spectral characteristics. Most of the X-ray flux arises in such interactions, not in the diffuse interior of the supernova remnant. Additional observations at optical and radio wavelengths support this account of the existing interstellar medium and its role in shaping the Cygnus Loop, and they demonstrate that the southeast knot is not a small cloud that the blast wave has engulfed. These data are consistent with rapid equilibration of electron and ion temperatures behind the shock front, and the current blast wave velocity v_{bw} approx 330 km/s. Most of this area does not show strong evidence for non-equilibrium ionization conditions, which may be a consequence of the high densities of the bright emission regions.Comment: To appear in ApJ, April 1, 200

Results of recent NASA research on low-speed aerodynamic characteristics of supersonic cruise aircraft

The relatively low values of lift-curve slope produced by highly swept arrow wings, coupled with the low scrape angle of the fuselage, resulted in relatively low values of take-off and approach lift coefficients. Through the use of more efficient high-lift systems and the application of propulsive-lift concepts, it is possible to optimize the engine-airframe design for maximum range potential and also to provide good low-speed performance. Nose strakes provide significant improvements in directional stability characteristics and the use of a propulsive lateral control system provides a solution to problems associated with inherently low levels of lateral control

Systematic derivation of a rotationally covariant extension of the 2-dimensional Newell-Whitehead-Segel equation

An extension of the Newell-Whitehead-Segel amplitude equation covariant under abritrary rotations is derived systematically by the renormalization group method.Comment: 8 pages, to appear in Phys. Rev. Letters, March 18, 199

Dynamics of a two-level system strongly coupled to a high-frequency quantum oscillator

Recent experiments on quantum behavior in microfabricated solid-state systems suggest tantalizing connections to quantum optics. Several of these experiments address the prototypical problem of cavity quantum electrodynamics: a two-level system coupled to a quantum harmonic oscillator. Such devices may allow the exploration of parameter regimes outside the near-resonance and weak-coupling assumptions of the ubiquitous rotating-wave approximation (RWA), necessitating other theoretical approaches. One such approach is an adiabatic approximation in the limit that the oscillator frequency is much larger than the characteristic frequency of the two-level system. A derivation of the approximation is presented and the time evolution of the two-level-system occupation probability is calculated using both thermal- and coherent-state initial conditions for the oscillator. Closed-form evaluation of the time evolution in the weak-coupling limit provides insight into the differences between the thermal- and coherent-state models. Finally, potential experimental observations in solid-state systems, particularly the Cooper-pair box--nanomechanical resonator system, are discussed and found to be promising.Comment: 16 pages, 11 figures; revised abstract; some text revisions; added two figures and combined others; added references. Submitted to Phys. Rev.