Utilization of a canine cancer cell line (FACC) panel in comparative and translational studies of gene expression and drug sensitivity

Includes bibliographical references.2015 Summer.Canine cancer is the leading cause of death in adult dogs. The use of the canine cancer model in translational research is growing in popularity due to the many biologic and genetic similarities it shares with human cancers. Cancer cell tissue culture has long been an established tool for expanding our understanding of cancer processes and for development of novel cancer treatments. With the high rate of genomic advancements in cancer research over the last decade human cancer cell line panels that combine pharmacologic and genomic information have proven very helpful in elucidating the complex relationships between gene expression and drug response in cancer. We have assembled a panel of canine cancer cell lines at the Flint Animal Cancer Center (FACC) at Colorado State University to be utilized in a similar fashion as a tool to advance canine cancer research. The purpose of these studies is to describe the characteristics of the FACC panel with the available genomic and drug sensitivity data we have generated, and to show its utility in comparative and translational oncology by focusing specifically on canine melanoma and osteosarcoma. We were able to confirm our panel of cell lines as being of canine origin and determined their genetic fingerprint through PCR and microsatellite analyses, creating a point of reference for validation in future studies and collaborations. Gene expression microarray analysis allowed for further molecular characterization of the panel, showing that similar tumor types tended to cluster together based on general as well as cancer specific gene expression patterns. In vitro studies that measure phenotypic differences in the panel can be coupled with genomic data, resulting in the identification of potential gene targets worthy of further exploration. We also showed that human and canine cancer cells are similarly sensitive to common chemotherapy. Next we utilized the FACC panel in a comparative analysis to determine if signaling pathways important in human melanoma were also activated and sensitive to targeted inhibition in canine melanoma. We were able to show that despite apparent differences in the mechanism of pathway activation, human and canine melanoma tumors and cell lines shared constitutive signaling of the MAPK and PI3K/AKT pathways, and responded similarly to targeted inhibition. These data suggest that studies involving pathway-targeted inhibition in either canine or human melanoma could potentially be directly translatable to each other. Evidence of genetic similarities between human and canine cancers led us to ask whether or not non-pathway focused gene expression models for predicting drug sensitivity could be developed in an interspecies manner. We were able to show that models built on canine datasets using human derived gene signatures successfully predicted response to chemotherapy in canine osteosarcoma patients. When compared to a large historical cohort, dogs that received the treatment our models predicted them to be sensitive to lived significantly longer disease-free. Taken together, these studies show that human and canine cancers share strong molecular similarities that can be used advantageously to develop better treatment strategies in both species

Metropolitan Planning and the Phenomenon of Reurbanisation: The Example of Liverpool

This paper considers the process and dynamics of reurbanisation and its implications for metropolitan planning. After brief consideration of reurbanisation trends in the UK, through a case study of the city of Liverpool in North West England, the paper explores how these recent trends of population regrowth and changing patterns of housing production (including purpose-built student accommodation) have affected the social structure of the city and what are the implications for planning policy? The paper concludes that population regrowth has been associated with increased spatial social segregation but is likely to continue and will shape future metropolitan planning

EHR-Based Care Coordination Performance Measures in Ambulatory Care

Describes electronic health record-based measures for assessing coordination in referrals, including information communicated with referral, communication to patient, and specialist report to primary care physician. Offers preliminary evaluation findings

Adsorption of hydrogen sulphide over rhodium/silica and rhodium/alumina at 293 and 873 K, with co-adsorption of carbon monoxide and hydrogen

In this study, we have examined the adsorption of hydrogen sulphide and carbon monoxide over rhodium/silica and rhodium/alumina catalysts. Adsorption of hydrogen sulphide was measured at 293 and 873 K and at 873 K in a 1:1 ratio with hydrogen. At 293 K, over Rh/silica, hydrogen sulphide adsorption capacity was similar to that of carbon monoxide; however, over Rh/alumina, the carbon monoxide adsorption capacity was higher, probably due to the formation of RhI(CO)2. Over Rh/silica, the primary adsorbed state was HS(ads), in contrast to Rh/alumina, where the H2:S ratio was 1:1 indicating that the adsorbed state was S(ads). Competitive adsorption between CO and H2S over Rh/silica and Rh/alumina revealed adsorption sites on the metal that only adsorbed carbon monoxide, only adsorbed hydrogen sulphide or could adsorb both species. At 873 K, hydrogen sulphide adsorption produced the bulk sulphide Rh2S3; however, when a 1:1 H2:H2S mixture was used formation of the bulk sulphide was inhibited and a reduced amount of hydrogen sulphide was adsorbed

School Finance Reform: Do Equalized Expenditures Imply Equalized Teacher Salaries?

This is the publisher's version, also available electronically from "http://www.mitpressjournals.org".Kentucky is a poor, relatively rural state that contrasts greatly with the relatively urban and wealthy states typically the subject of education studies employing large-scale administrative data. For this reason, Kentucky's experience of major school finance and curricular reform is highly salient for understanding teacher labor market dynamics. This study examines the time path of teacher salaries in Appalachian and non-Appalachian Kentucky using a novel teacher-level administrative data set. Our results suggest that the Kentucky Education Reform Act (KERA) provided a salary boost for all Appalachian teachers, resulting in a wage premium for teachers of low and medium experience and equalizing pay across Appalachian and non-Appalachian districts for teachers of high experience. However, we find that Appalachian salaries fell back to the level of non-Appalachian teachers roughly a decade following reform, at which point the pre-KERA remuneration patterns re-emerge

Hong-Ou-Mandel interferometer with cavities: theory

We study the number of coincidences in a Hong-Ou-Mandel interferometer exit whose arms have been supplemented with the addition of one or two optical cavities. The fourth-order correlation function at the beam-splitter exit is calculated. In the regime where the cavity length are larger than the one-photon coherence length, photon coalescence and anti-coalescence interference is observed. Feynman's path diagrams for the indistinguishable processes that lead to quantum interference are presented. As application for the Hong-Ou-Mandel interferometer with two cavities, it is discussed the construction of an optical XOR gate

Optical analog of Rabi oscillation suppression due to atomic motion

The Rabi oscillations of a two-level atom illuminated by a laser on resonance with the atomic transition may be suppressed by the atomic motion through averaging or filtering mechanisms. The optical analogs of these velocity effects are described. The two atomic levels correspond in the optical analogy to orthogonal polarizations of light and the Rabi oscillations to polarization oscillations in a medium which is optically active, naturally or due to a magnetic field. In the later case, the two orthogonal polarizations could be selected by choosing the orientation of the magnetic field, and one of them be filtered out. It is argued that the time-dependent optical polarization oscillations or their suppression are observable with current technology.Comment: 10 pages, 10 figure

Solvation entropy, enthalpy and free energy prediction using a multi-task deep learning functional in 1D-RISM

Simultaneous calculation of entropies, enthalpies and free energies has been a long-standing challenge in computational chemistry, partly because of the difficulty in obtaining estimates of all three properties from a single consistent simulation methodology. This has been particularly true for methods from the Integral Equation Theory of Molecular Liquids such as the Reference Interaction Site Model which have traditionally given large errors in solvation thermodynamics. Recently, we presented pyRISM-CNN, a combination of the 1 Dimensional Reference Interaction Site Model (1D-RISM) solver, pyRISM, with a deep learning based free energy functional, as a method of predicting solvation free energy (SFE). With this approach, a 40-fold improvement in prediction accuracy was delivered for a multi-solvent, multi-temperature dataset when compared to the standard 1D-RISM theory [Fowles et al., Digital Discovery, 2023, 2, 177–188]. Here, we report three further developments to the pyRISM-CNN methodology. Firstly, solvation free energies have been introduced for organic molecular ions in methanol or water solvent systems at 298 K, with errors below 4 kcal mol−1 obtained without the need for corrections or additional descriptors. Secondly, the number of solvents in the training data has been expanded from carbon tetrachloride, water and chloroform to now also include methanol. For neutral solutes, prediction errors nearing or below 1 kcal mol−1 are obtained for each organic solvent system at 298 K and water solvent systems at 273–373 K. Lastly, pyRISM-CNN was successfully applied to the simultaneous prediction of solvation enthalpy, entropy and free energy through a multi-task learning approach, with errors of 1.04, 0.98 and 0.47 kcal mol−1, respectively, for water solvent systems at 298 K

Performance Measures Using Electronic Health Records: Five Case Studies

Presents the experiences of five provider organizations in developing, testing, and implementing four types of electronic quality-of-care indicators based on EHR data. Discusses challenges, and compares results with those from traditional indicators