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Antiproliferative effects of masitinib and imatinib against canine oral fibrosarcoma in vitro
Get PDFBackground:
Canine oral fibrosarcoma (COF) is one of the most common oral tumors in dogs and carries a guarded prognosis due to a lack of effective systemic therapeutic options. Mastinib and imatinib are two commonly used tyrosine kinase inhibitors (TKIs) in veterinary oncology but their potential efficacy against COF is uncharacterized. To begin investigating the rationale for use of these TKIs against COF, the present study tested for the presence TKI targets PDGFR-α, PDGFR-β, Kit, and VEGFR-2 and examined the in vitro effects on cell viability after TKI treatment alone or with doxorubicin.
Immunohistochemistry for PDGFR-α, PDGFR-β, Kit, and VEGFR-2 was performed in 6 COF tumor biopsies. Presence of these same receptors within 2 COF cell lines was probed by reverse transcription-polymerase chain reaction and, for those with mRNA detected, confirmed via western blot. Effects on cell viability were assessed using an MTS assay after masitinib or imatinib treatment alone (0-100 μM), or in combination with doxorubicin (0-3000 nM doxorubicin). Anti-PDGFRB siRNA knockdown was performed and the effect on cell viability quantified.
Results:
Expression of the TKI targets evaluated was similar between the 2 COF cell lines and the 6 COF tumor biopsies: PDGFR-α and PDGFR-β were detected in neoplastic cells from most COF tumor biopsies (5/6 and 6/6, respectively) and were present in both COF cell lines; KIT and KDR were not detected in any sample. Masitinib and imatinib IC50 values ranged from 7.9–33.4 μM, depending on the specific TKI and cell line tested. The addition of doxorubicin resulted in synergistic cytotoxicity with both TKIs. Anti-PDGFRB siRNA transfection reduced PDGFR-β protein expression by 77 % and 67 % and reduced cell viability by 24 % (p < 0.0001) and 28 % (0 = 0.0003) in the two cell lines, respectively.
Conclusions:
These results provide rationale for further investigation into the use of TKIs, possibly in combination with doxorubicin, as treatment options for COF.Keywords: Masitinib, Oral fibrosarcoma, Imatinib, Platelet-derived growth factor receptor, Do
Magma transport and olivine crystallization depths in Kīlauea's east rift zone inferred from experimentally rehomogenized melt inclusions
Get PDFConcentrations of H₂O and CO₂ in olivine-hosted melt inclusions can be used to estimate crystallization depths for the olivine host. However, the original dissolved CO₂ concentration of melt inclusions at the time of trapping can be difficult to measure directly because in many cases substantial CO₂ is transferred to shrinkage bubbles that form during post-entrapment cooling and crystallization. To investigate this problem, we heated olivine from the 1959 Kīlauea Iki and 1960 Kapoho (Hawai‘i) eruptions in a 1-atm furnace to temperatures above the melt inclusion trapping temperature to redissolve the CO₂ in shrinkage bubbles. The measured CO₂ concentrations of the experimentally rehomogenized inclusions (⩽590 ppm for Kīlauea Iki [n = 10]; ⩽880 ppm for Kapoho, with one inclusion at 1863 ppm [n = 38]) overlap with values for naturally quenched inclusions from the same samples, but experimentally rehomogenized inclusions have higher within-sample median CO₂ values than naturally quenched inclusions, indicating at least partial dissolution of CO₂ from the vapor bubble during heating. Comparison of our data with predictions from modeling of vapor bubble formation and published Raman data on the density of CO₂ in the vapor bubbles suggests that 55–85% of the dissolved CO₂ in the melt inclusions at the time of trapping was lost to post-entrapment shrinkage bubbles. Our results combined with the Raman data demonstrate that olivine from the early part of the Kīlauea Iki eruption crystallized at <6 km depth, with the majority of olivine in the 1–3 km depth range. These depths are consistent with the interpretation that the Kīlauea Iki magma was supplied from Kīlauea’s summit magma reservoir (∼2–5 km depth). In contrast, olivine from Kapoho, which was the rift zone extension of the Kīlauea Iki eruption, crystallized over a much wider range of depths (∼1–16 km). The wider depth range requires magma transport during the Kapoho eruption from deep beneath the summit region and/or from deep beneath Kīlauea’s east rift zone. The deeply derived olivine crystals and their host magma mixed with stored, more evolved magma in the rift zone, and the mixture was later erupted at Kapoho.This is the publisher’s final pdf. The published article is copyrighted by Elsevier and can be found at: http://www.sciencedirect.com/science/journal/00167037Keywords: Melt inclusions, Kīlauea, Geochemistry, Volcanology, Hawaiian geolog
Extent of the microbial biosphere in the oceanic crust
Get PDFWe estimate the depth of the 120°C isotherm by constructing crustal thermal gradients based on theoretical and observed conductive heat flux as a function of lithospheric age. We chose the 120°C isotherm because it is close to the upper limit for prokaryotic life, and therefore, the isotherm approximates the maximum depth at which life can persist in the ocean crust. The depth of the potential microbial biosphere increases with lithospheric age from approximately 0.5 to 1 km for 1 Ma lithosphere to as much as 5 km at a subduction age of 180 Ma. We use global models of oceanic plate creation to estimate the volume of crust occupied by the biosphere today and throughout geologic time. Presently, the volume of the ocean crust that is capable of containing life is similar to the volume of the oceans (∼1018 m3). Depending on the model used for the growth of continental crust, the volume of rock available to house the subsurface biosphere may have remained constant or doubled since the Archean. Although the thermal models presented here provide estimates for the potential depth and volume of rock in which microbes may live, the biomass in this volume is not well constrained. Using a previously published model, the prokaryotic biomass in the igneous ocean crust is estimated to exceed that in all aquatic and soil environments and is similar to that in the continental subsurface and in marine sediment. Most of the crustal biomass beneath the sediments is likely contained within the extrusive layer, and this has probably been the case since microbes first colonized the oceanic crust in the Archean.Keywords: Microbial biosphere, Ocean crust, Thermal structur
Differential feeding by marine flagellates on growing versus starving, and on motile versus nonmotile, bacterial prey
Get PDFPrevious work has demonstrated selective feeding by bacterivorous protists on the of prey size. Other prey characteristics may also affect protist grazing rates. In this relative uptake rates of fluorescently labeled bacterial (FLB) cells made from starving bacteria (S-FLB), and of live-stained motile vs non-motile bacteria by marine We also determined relative growth rates and digestion times for flagellates fed starved bacteria. A natural assemblage of marine flagellates and a flagellate isolate, showed lower (p < 0.001) clearance rates on S-FLB than on G-FLB, which could be grazing by the flagellates. Moreover, flagellates showed longer (p < 0.001) prey times when feeding on S-FLB than on G-FLB. The carbon-based gross growth fed starved bacteria was nearly twice that of flagellates fed growing bacteria: 38.5% respectively. Uptake rates by flagellates of several live-stained bacteria (LSB) of strains were compared with uptake rates of heat-killed FLB made from the same cultures. Clearance rates were significantly higher for LSB compared to FLB only for differences in uptake rates were observed for non-motile bacteria. Although FLB for non-motile bacteria, use of FLB may lead to underestimation of actual grazing comprise a significant fraction of the total bacterial assemblage. Our results suggest starved bacteria results in a more efficient transfer of biomass to higher trophic on growing bacteria; (2) use of motile LSB in prey uptake experiments should yield of bacterivory compared to rates estimated using heat-killed or non-motile labeled factors affecting predator-prey dynamics may be important in regulating elemental microbial food webs.Keywords: Microbial loop, Bacterivory, Flagellat
Scanless Fast Handoff Technique Based on Global Path Cache for WLANs
Get PDFWireless LANs (WLANs) have been widely adopted and are more convenient as they are inter-connected as wireless campus networks and wireless mesh networks. However, time-sensitive multimedia applications, which
have become more popular, could suffer from long end-to-end latency in WLANs.
This is due mainly to handoff delay, which in turn is caused by channel
scanning. This paper proposes a technique called Global Path-Cache (GPC) that
provides fast handoffs in WLANs. GPC properly captures the dynamic
behavior of the network and MSs, and provides accurate next-AP predictions to
minimize the handoff latency. Moreover, the handoff frequencies are treated
as time-series data, thus GPC calibrates the prediction models based on short
term and periodic behaviors of mobile users. Our simulation study shows that
GPC virtually eliminates the need to scan for APs during handoffs and results
in much better overall handoff delay compared to existing methods.Keywords: Mobility prediction, Time series analysis, Handoff, Wireless LANs, Channel scannin
Attractiveness of Fermentation and Related Products to Spotted Wing Drosophila (Diptera: Drosophilidae)
Get PDFLaboratory screening bioassays and field trapping experiments of spotted wing drosophila flies, Drosophila suzukii (Matsumura) (Diptera: Drosophilidae), were conducted to determine the attractiveness of 17 compounds as well as to compare attractant efficiency during peak fruit ripeness and postharvest captures late in the season. Compounds structurally related to each of the fermentation products acetic acid, ethanol, ethyl acetate, and 2-phenethyl alcohol were screened for attractiveness compared with a soap water control in greenhouse cage bioassays. The compounds determined to be attractive in the greenhouse bioassay (methanol, ethanol, propanol, formic acid, acetic acid, ethyl acetate, propyl acetate, phenethyl acetate, phenethyl propionate, and phenethyl butyrate) were individually tested in the field added to apple cider vinegar (ACV). The acids were also tested individually in neutralized ACV (NACV; pH ≈ 7). Combinations of the compounds were tested in NACV. The capture numbers in ACV traps were not significantly increased by the addition of any of the compounds tested, although significant deterrent effects of some of the compounds allowed differences between treatments to be observed. Compounds that are most prevalent in wine and vinegar (methanol, ethanol, acetic acid, and ethyl acetate) as well as phenethyl propionate and phenethyl butyrate were less deterrent than the other compounds tested in the field. Captures during peak fruit ripeness were compared with the postharvest period when fruit hosts were not available or were overripe. Although the total number of flies captured late in the season was lower, the trends in treatment performance were similar, indicating a consistent performance of these baits from peak fruit ripeness through postharvest.Keywords: monitoring, spotted wing drosophila, bait, trapping, apple cider vinega
Changes in the atmospheric helium isotope ratio over the past 40 years
Get PDFWe have compared the helium isotope ratio in five
samples of Pacific marine air spanning the 40 year period
between 1973 and 2013 against a secondary gas standard. In
a separate experiment we directly compared the ³He/⁴He
ratio in air samples collected in 1973 and 2013 at the same
location in La Jolla, California, eliminating any geographical
bias. Both experiments are consistent with zero time rate of
change for atmospheric ³He/⁴He. Our best estimate for the
rate of change of the ³He/⁴He ratio in Pacific marine air is
-0.0014 ± 0.0045%/yr (2σ), indicating that air helium is still
a valid standard for terrestrial helium isotope measurements.Keywords: natural gas, atmospheric, isotopes, helium, ai
Browsing for information on the web and in the file system
Get PDFBrowsing is one of the methods used for finding and refinding information on the web or in the file local system and there are opportunities to avoid this, particularly if that information is revisited frequently. We present empirical results from a field study contrasting patterns of browsing to local and web information and we qualify the cost that this navigation method incurs. In addition, we provide an improved method for defining revisit behavior and report on the level of revisits during our study. Our findings have implications for solution development that reduce user effort for finding and refinding information.Keywords: navigation, finding, Information Search and Retrieval, Information Storage and Retrieval, Information interfaces and presentation, refinding, files, web pages, Browsin
An Investigation on Transient Critical Heat Flux and the Prompting Conditions
Get PDFThe collective understanding of the critical heat flux phenomenon is crucial to the safety and operational power limits of every nuclear and petrochemical power plant in the world. To define the maximum heat transfer capability in the postulated reactivity-initiated accident in a nuclear reactor, the mechanisms that trigger the departure from nucleate boiling during fast-power transients must be better understood.
This research investigates the CHF phenomenon under rapid power excursions (1.5-5,000ms), subcoolings of 15 and 25K, and coolant flow-rates corresponding to Reynolds number up to 5700. This was achieved by using a high-speed camera to record images of a 20x5mm Nickel-201 heater foil in a de-ionized water flow-loop via joule heating . In the observed flow regimes up to Re=5,700, the CHF value is observed to increase towards 10 MW/m2 under power ramps period smaller than ~100ms for both subcoolings. The CHF value is observed up to 1MW/m2 higher for the 25K series than 15K, due to less of a thermal barrier during heating.
When comparing the pool-boiling (Re=0) conditions to the Re=5,700 tests, the increased flow will shift the large tau CHF values up to 2MW/m2 higher in slow transients larger than 500ms. In the intermediate flow conditions of Re=2,900 and Re=4,100 there is great repeatability of the CHF value, especially in fast transient cases of tau smaller than 150ms.
After analyzing all the burn-out videos, it has been concluded that the period and flow-rate both heavily influence the footprint of the film as well as the location of its generation. For CHF tests ramping power faster than a tau of 40ms, it may be expected for film formation to be almost as large as the center rectangle of the heater. In very slow transient experiments greater than a tau of 100ms, the localized film takes the geometrical shape of a rectangle spanning the 5mm width of the ribbon and a few millimeters length.
This thesis gives detail to 41 unique CHF occurrences tracking surface temperature, heat flux, and ultimately the heat transfer coefficient (h) during each boiling crisis. This coefficient was tracked oscillating values between 1,000 and 10,000W/m٠K for all tests, where the onset of CHF would usually occur in the final approach to 10,000
Global solutions to regional problems : collecting global expertise to address the problem of harmful cyanobacterial blooms. A Lake Erie case study
Get PDFIn early August 2014, the municipality of Toledo, OH (USA) issued a ‘do not drink’ advisory on their water supply directly affecting over 400,000 residential customers and hundreds of businesses (Wilson, 2014). This order was attributable to levels of microcystin, a potent liver toxin, which rose to 2.5 μg L⁻¹ in finished drinking water. The Toledo crisis afforded an opportunity to bring together scientists from around the world to share ideas regarding factors that contribute to bloom formation and toxigenicity, bloom and toxin detection as well as prevention and remediation of bloom events. These discussions took place at an NSF- and NOAA-sponsored workshop at Bowling Green State University on April 13 and 14, 2015. In all, more than 100 attendees from six countries and 15 US states gathered together to share their perspectives. The purpose of this review is to present the consensus summary of these issues that emerged from discussions at the Workshop. As additional reports in this special issue provide detailed reviews on many major CHAB species, this paper focuses on the general themes common to all blooms, such as bloom detection, modeling, nutrient loading, and strategies to reduce nutrients.This is the publisher’s final pdf. The published article is copyrighted by Elsevier and can be found at: http://www.journals.elsevier.com/harmful-algae/Keywords: Nitrogen, CHAB, Phosphorus, Microcystin, Cyanobacteria, Lake Eri