The contribution of roads to forest fragmentation has not been adequately analyzed. We quantified fragmentation due to roads in a 30,213‐ha section of the Medicine Bow‐Routt National Forest in sout heastern Wyoming with several indices of landscape structure using a geographic information system. The number of patches, mean patch area, mean interior area, mean area of edge influence, mean patch perimeter, total perimeter, and mean patch shape identified patch‐ and edge‐related landscape changes. Shannon‐Wiener diversity, dominance, contagion, contrast, and angular second moment indicated effects on landscape diversity and texture. Roads added to forest fragmentation more than clearcuts by dissecting large patches into smaller pieces and by converting forest interior habitat into edge habitat. Edge habitat created by roads was 1.54–1.98 times the edge habitat created by clearcuts. The total landscape area affected by clearcuts and roads was 2.5–3.5 times the actual area occupied by these disturbances. Fragmentation due to roads could be minimized if road construction is minimized or rerouted so that its fragmentation effects are reduced. Geographic information system technology can be used to quantify the potential fragmentation effects of individual roads and the cumulative effects of a road network on landscape structure.

Deletion at chromosome 3p21.3 is the earliest and the most frequently observed genetic alteration in lung cancer, suggesting that the region contains tumor suppressor gene(s) (TSG). Identification of those genes may lead to the development both of biomarkers to identify high-risk individuals and novel therapeutics. Previously, we cloned the H37/Luca15/RBM5 gene from 3p21.3 and showed its TSG characteristics. To investigate the physiologic function of H37 in the lung and its mechanism of tumor suppression, we have stably transfected H37 into A549 non-small cell lung cancer cells. A549/H37 cells show significant growth inhibition compared with the vector controls by in vitro and in vivo cell proliferation assays. Using this lung cancer cell model, we have found that the molecular mechanism of H37 tumor suppression involves both cell cycle (G 1 ) arrest and apoptosis. To further define H37's function in cell cycle/apoptotic pathways, we investigated differential expression profiles of various cell cycle and apoptosis regulatory proteins using Western blot analysis. Both cyclin A and phophorylated RB levels were decreased in H37-transfected cells, whereas expression of Bax protein was increased. Mitochondrial regulation of apoptosis further downstream of Bax was investigated, showing change in the mitochondrial membrane potential, cytochrome c release into the cytosol, and enhanced caspase-9 and caspase-3 activities. We also report that H37 may mediate apoptosis in a p53-independent manner, and Bax knockdown by small interfering RNA suggests Bax plays a functional role downstream of H37. Lastly, we proposed a tumor suppression model of H37 as a post-transcriptional regulator for cell cycle/apoptotic-related proteins.

Quaking aspen (Populus tremuloides Michx.) is a long‐lived clonal species in which many genetically identical stems (ramets) arise from a common root system. Establishment by seed is extremely rare in the Rocky Mountain region, where most clones that exist today are thought to have established hundreds or thousands of years ago. However, recruitment of new genetic individuals through sexual reproduction has occurred periodically throughout the Holocene, and widespread establishment of seedling aspen occurred in Yellowstone National Park, USA, following the extensive 1988 fires. We combined extensive survey methods with manipulative experiments to investigate the patterns and mechanisms of new aspen genet establishment, growth, and survival during their first decade of development. Excavation and aging of 173 aspen stems in 1996 demonstrated that 65% had established within the first three years after the 1988 fires, and that none pre‐dated 1988. Random amplified polymorphic DNA (RAPD) genetic analyses revealed that 92% of the plants were genetically distinct individuals, and 8% were ramets. Annual surveys of 22 permanently marked aspen seedling plots revealed that 24% of 417 seedlings tallied in 1996 had died by 2000. However, mortality varied greatly among the 22 plots, from <10% to >40%, with greater mortality at lower elevations and where soil organic matter was low. To evaluate the mechanisms underlying seedling persistence or mortality, we constructed exclosures in three sites to protect aspen seedlings from ungulate browsing, and applied four experimental treatments from 1996 to 1998: (1) clipping of current year's growth to simulate browsing, (2) removal of potential competitors including lodgepole pine (Pinus contorta var. latifolia) saplings and herbaceous plants, (3) clipping and competitor removal, and (4) control, i.e., no treatment except protection from browsing. Clipping prevented stem elongation, but removing competitors had no significant effect on height growth of aspen seedlings. Even with protection from browsing, most aspen stems grew slowly (mean increment <25 cm from 1996 to 2000), and many died from causes unrelated to herbivory. Nevertheless, some individuals were >2 m tall in 2003 and appeared vigorous. The aspen cohort that germinated after the 1988 fires appears to be in the earliest stage of a long‐term population process, a process that likely will entail a shift from many genetically distinct individuals but few ramets, to relatively few genets having numerous ramets. We predict that many or most of the post‐1988 aspen seedlings will die within the next few decades, with little lasting effect on broad‐scale vegetation patterns or postfire successional trajectories. However, some new genets appear likely to survive and to establish new aspen clones, with potentially important consequences for demographic and genetic structure of the Yellowstone aspen population.

Abstract. Metastatic cancer is a life-threatening illness with a predictably fatal outcome, thereby representing a major unmet medical need. In 2003, Rexin-G™ became the world's first targeted injectable vector approved for clinical trials in the treatment of intractable metastatic disease. Uniquely suited, by design, to function within the context of the human circulatory system, Rexin-G is a pathotropic (disease-seeking) gene delivery system bearing a designer killer gene; in essence, a targeted nanoparticle that seeks out and selectively accumulates in metastatic sites upon intravenous infusion. The targeted delivery of the cytocidal gene to primary tumors and metastatic foci, in effective local concentrations, compels both cancer cells and tumor-associated neovasculature to self-destruct, without causing untoward collateral damage to non-target organs. In this study: i) we report the results of three distinctive clinical studies which demonstrate the initial proofs of concept, safety, and efficacy of Rexin-G when used as a single agent for advanced or metastatic cancer, ii) we introduce the quantitative foundations of an innovative personalized treatment regimen, designated the 'Calculus of Parity', based on a patient's calculated tumor burden, iii) we propose a refinement of surrogate end-points commonly used for defining success in cancer therapy, and iv) we map out a strategic plan for the accelerated approval of Rexin-G based on the oncologic Threshold of Credibility paradigm being developed by the Food and Drug Administration.

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