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

Titanium alloy stress corrosion cracking in presence of dinitrogen tetroxide

Study resulting in a satisfactory stress corrosion cracking test with extremely consistent results produced six new analytical methods. Methods detect and determine differences in the minor constituent composition of different types of dinitrogen tetroxide

Crystal structure analysis of intermetallic compounds

Study concerns crystal structures and lattice parameters for a number of new intermetallic compounds. Crystal structure data have been collected on equiatomic compounds, formed between an element of the Sc, Ti, V, or Cr group and an element of the Co or Ni group. The data, obtained by conventional methods, are presented in an easily usable tabular form

Movement and habitat use of two aquatic turtles (\u3cem\u3eGraptemys geographic\u3c/em\u3e and \u3cem\u3eTrachemys scripta\u3c/em\u3e) in an urban landscape

Our study focuses on the spatial ecology and seasonal habitat use of two aquatic turtles in order to understand the manner in which upland habitat use by humans shapes the aquatic activity, movement, and habitat selection of these species in an urban setting. We used radiotelemetry to follow 15 female Graptemys geographica (common map turtle) and each of ten male and female Trachemys scripta (red-eared slider) living in a man-made canal within a highly urbanized region of Indianapolis, IN, USA. During the active season (between May and September) of 2002, we located 33 of the 35 individuals a total of 934 times and determined the total range of activity, mean movement, and daily movement for each individuals. We also analyzed turtle locations relative to the upland habitat types (commercial, residential, river, road, woodlot, and open) surrounding the canal and determined that the turtles spent a disproportionate amount of time in woodland and commercial habitats and avoided the road-associated portions of the canal. We also located 21 of the turtles during hibernation (February 2003), and determined that an even greater proportion of individuals hibernated in woodland-bordered portions of the canal. Our results clearly indicate that turtle habitat selection is influenced by human activities; sound conservation and management of turtle populations in urban habitats will require the incorporation of spatial ecology and habitat use data

Simulation support for internet-based energy services

The rapidly developing Internet broadband network offers new opportunities for deploying a range of energy, environment and health-related services for people in their homes and workplaces. Several of these services can be enabled or enhanced through the application of building simulation. This paper describes the infrastructure for e-services under test within a European research project and shows the potential for simulation support for these services

The role of ECL2 in CGRP receptor activation: a combined modelling and experimental approach

The calcitonin gene-related peptide (CGRP) receptor is a complex of a calcitonin receptor-like receptor (CLR), which is a family B G-protein-coupled receptor (GPCR) and receptor activity modifying protein 1. The role of the second extracellular loop (ECL2) of CLR in binding CGRP and coupling to Gs was investigated using a combination of mutagenesis and modelling. An alanine scan of residues 271–294 of CLR showed that the ability of CGRP to produce cAMP was impaired by point mutations at 13 residues; most of these also impaired the response to adrenomedullin (AM). These data were used to select probable ECL2-modelled conformations that are involved in agonist binding, allowing the identification of the likely contacts between the peptide and receptor. The implications of the most likely structures for receptor activation are discussed.</jats:p

Promoting Social Justice through Service-Learning in Urban Teacher Education: The Role of Student Voice

Although service-learning is becoming more common in teacher education programs (Anderson & Erickson 2003), few detailed case descriptions show how service-learning can help to promote a social justice orientation for prospective teachers. A comparative descriptive analysis of projects within two teacher preparation programs--one focused on training undergraduates and one focused on training graduate students--illustrates how service-learning, when undergirded by student voice work, prepares prospective educators to teach for social justice in urban classrooms. We identify commonalities in our two approaches to integrating service-learning and student voice into the teacher education curriculum, and we show how our distinctive efforts support prospective teachers in developing the relationships, reflections, and practices they need to become effective educators of urban youth

Descriptive ecology of a turtle assemblage in an urban landscape

We studied turtle populations inhabiting a canal and a lake (both man-made) within a heavily disturbed, urban setting. Six aquatic and semi-aquatic turtle species were collected in both habitats: spiny softshell turtle (Apolone spinifera), painted turtle (Chrysemys picta), common snapping turtle (Chelydra serpentina), common map turtle (Graptemys geographica), common musk turtle (Sternotherus odoratus) and red-eared slider (Trachemys scripta). While G. geographica was the most common species in the canal habitat, T. scripta was most common in the lake habitat. We describe patterns of sexual size dimorphism and sex ratios for the three most abundant species (G. geographica, T. scripta and S. odoralus). We discuss our data in light of problems facing turtle assemblages in urban settings

Hover Acoustic Characteristics of the XV-15 with Advanced Technology Blades

An experiment has been performed to investigate the far-field hover acoustic characteristics of the XV-15 aircraft with advanced technology blades (ATB). An extensive, high-quality, far-field acoustics data base was obtained for a rotor tip speed range of 645-771 ft/s. A 12-microphone, 500-ft radius semicircular array combined with two aircraft headings provided acoustic data over the full 360-deg azimuth about the aircraft with a resolution of 15 deg. Altitude variations provided data from near in-plane to 45 deg below the rotor tip path plane. Acoustic directivity characteristics in the lower hemisphere are explored through pressure time histories, narrow-band spectra, and contour plots. Directivity patterns were found to vary greatly with azimuth angle, especially in the forward quadrants. Sharp positive pressure pulses typical of blade-vortex interactions were found to propagate aft of the aircraft and were most intense at 45 deg below the rotor plane. Modest overall sound pressure levels were measured near in-plane indicating that thickness noise is not a major problem for this aircraft when operating in the hover mode with ATB. Rotor tip speed reductions reduced the average overall sound pressure level (dB (0.0002 dyne/cm(exp 2)) by nearly 8 dB in-plane, and 12.6 deg below the rotor plane