An increase in N-Ras expression is associated with development of hormone refractory prostate cancer in a subset of patients

Protein expression of H, K and N-Ras was assessed in hormone sensitive and hormone refractory prostate tumour pairs from 61 patients by immunohistochemistry. Expression of H-Ras and K- Ras was not associated with any known clinical parameters. In contrast an increase in N-Ras membrane expression in the transition from hormone sensitive to hormone refractory prostate cancer was associated with shorter time to relapse (p=0.01) and shorter disease specific survival (p=0.008). In addition, patients with an increase in N-Ras membrane expression had lower levels of PSA at relapse (p=0.02) and expression correlated with phosphorylated MAP kinase (p=0.010) and proliferation index (Ki67, p=0.02). These results suggest that in a subgroup patients N-Ras expression is associated with development of hormone refractory prostate cancer via activation of the MAP kinase cascade

Themed section

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109995/1/bph13028.pd

Positive allosteric modulators of the μ‐opioid receptor: a novel approach for future pain medications

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109803/1/bph12599.pd

Pressure sensing through Piezo channels controls whether cells migrate with blebs or pseudopods.

Blebs and pseudopods can both power cell migration, with blebs often favored in tissues, where cells encounter increased mechanical resistance. To investigate how migrating cells detect and respond to mechanical forces, we used a "cell squasher" to apply uniaxial pressure to Dictyostelium cells chemotaxing under soft agarose. As little as 100 Pa causes a rapid (<10 s), sustained shift to movement with blebs rather than pseudopods. Cells are flattened under load and lose volume; the actin cytoskeleton is reorganized, with myosin II recruited to the cortex, which may pressurize the cytoplasm for blebbing. The transition to bleb-driven motility requires extracellular calcium and is accompanied by increased cytosolic calcium. It is largely abrogated in cells lacking the Piezo stretch-operated channel; under load, these cells persist in using pseudopods and chemotax poorly. We propose that migrating cells sense pressure through Piezo, which mediates calcium influx, directing movement with blebs instead of pseudopods

Irrigation demand model

Presented at the 2002 USCID/EWRI conference, Energy, climate, environment and water - issues and opportunities for irrigation and drainage on July 9-12 in San Luis Obispo, California.Includes bibliographical references.Like many jurisdictions in North America, the irrigation industry in Alberta, Canada has found it necessary to intensively examine its future state of development, in view of substantially increased competition for a finite supply of available water. In order to do so, it was recognized that available technical science and assessment tools needed to be up-dated and expanded. Specifically, the opportunity and ability to utilize state-of-the-art computer modelling techniques could allow much more detailed and varied analyses to be carried out. As part of a broad scope basin water management planning review, the development of a complex irrigation demand model was undertaken. After several years of detailed and intensive software development, a suite of data input, irrigation simulation and analysis tools has been derived. The application of the irrigation demand model component provides for very detailed projections of daily water requirements, consumptive use, conveyance and application losses, as well as return flows. Annual and multi-year irrigation demands can be determined in conjunction with water supply conditions that reflect both the interrelationship with the vagaries of climate as well as varying scenarios of development within the industry. In particular, output from the application of the whole suite of tools indicates both the projected level of water supply deficits as well as the potential impacts of those shortages

Service Learning Models Connecting Computer Science to the Community

Service learning is an educational experience that enables students to apply material learned in the classroom by volunteering in a real-world situation. This paper provides a brief review of service learning and describes two models that the computer science department at Saint Anselm College implemented successfully

Challenges for Opioid Receptor Nomenclature

Recent developments in the study of the structure and function of opioid receptors raise significant challenges for the definition of individual receptor types and the development of a nomenclature that precisely describes isoforms that may subserve different functions in vivo. Presentations at the 2013 meeting of the International Narcotics Research Conference in Cairns, Australia, considered some of the new discoveries that are now unravelling the complexities of opioid receptor signalling. Variable processing of opioid receptor messenger RNAs may lead to the presence of several isoforms of the μ receptor. Each opioid receptor type can function either as a monomer or as part of a homo- or heterodimer or higher multimer. Additionally, recent evidence points to the existence of agonist bias in the signal transduction pathways activated through μ receptors, and to the presence of regulatory allosteric sites on the receptors. This brief review summarizes the recent discoveries that raise challenges for receptor definition and the characterization of signal transduction pathways activated by specific receptor forms. LINKED ARTICLES: This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.NHMRC 104596

Correlated sampling in quantum Monte Carlo: a route to forces

In order to find the equilibrium geometries of molecules and solids and to perform ab initio molecular dynamics, it is necessary to calculate the forces on the nuclei. We present a correlated sampling method to efficiently calculate numerical forces and potential energy surfaces in diffusion Monte Carlo. It employs a novel coordinate transformation, earlier used in variational Monte Carlo, to greatly reduce the statistical error. Results are presented for first-row diatomic molecules.Comment: 5 pages, 2 postscript figure