Experimental and topological determination of the pressure-temperature phase diagram of morniflumate, a pharmaceutical ingredient with anti-inflammatory properties

The pressure-temperature phase diagram of morniflumate (niflumic acid ß-morpholinoethyl ester) has been obtained by high-pressure thermal analysis. In addition, calorimetric melting data (TI¿L = (348.1 ± 0.4) K and ¿HI¿L = (89 ± 2) J·g-1) and the specific volumes of the solid and the liquid state have been obtained under normal pressure. Comparison of the measured high-pressure melting data with the equilibrium curve obtained through the Clapeyron equation indicates that the initial slopes are the same (dP/dT = (2.96 ± 0.06) MPa·K-1) at the melting point under normal pressure. The fact that the Clapeyron equation can be used to construct topological phase diagrams may be of interest for the food and pharmaceutical industries.Peer ReviewedPostprint (author's final draft

Combined cetuximab and trastuzumab are superior to gemcitabine in the treatment of human pancreatic carcinoma xenografts

Background: Pancreatic carcinoma remains a treatment-refractory cancer with a poor prognosis. Here, we compared anti-epidermal growth factor receptor (EGFR) and anti-HER2 monoclonal antibodies (2mAbs) injections with standard gemcitabine treatment on human pancreatic carcinoma xenografts. Materials and methods: Nude mice, bearing human pancreatic carcinoma xenografts, were treated with either combined anti-EGFR (cetuximab) and anti-HER2 (trastuzumab) or gemcitabine, and tumor growth was observed. Results and conclusion: In first-line therapy, mice survival was significantly longer in the 2mAbs group compared with gemcitabine (P < 0.0001 for BxPC-3, P = 0.0679 for MiaPaCa-2 and P = 0.0019 for Capan-1) and with controls (P < 0.0001). In second-line therapy, tumor regressions were observed after replacing gemcitabine by 2mAbs treatment, resulting in significantly longer animal survival compared with mice receiving continuous gemcitabine injections (P = 0.008 for BxPC-3, P = 0.05 for MiaPaCa-2 and P < 0.001 for Capan-1). Therapeutic benefit of 2mAbs was observed despite K-Ras mutation. Interestingly, concerning the mechanism of action, coinjection of F(ab′)2 fragments from 2mAbs induced significant tumor growth inhibition, compared with controls (P = 0.001), indicating that the 2mAbs had an Fc fragment-independent direct action on tumor cells. This preclinical study demonstrated a significant improvement of survival and tumor regression in mice treated with anti-EGFR/anti-HER2 2mAbs in first- and second-line treatments, compared with gemcitabine, independently of the K-Ras statu

Colour response in western flower thrips varies intraspecifically

Discrepancies in the published research as to the attraction of the economically important pest western flower thrips (WFT) to different colours confounds the optimisation of field traps for pest management purposes. We considered whether the different experimental conditions of independent studies could have contributed to this. Therefore, the behavioural response (i.e., landings) to different colour cues of two WFT laboratory populations from Germany (DE) and The Netherlands (NL), which had previously been independently shown to have different colour preferences, were tested in the same place, and under the same experimental conditions. Single-choice wind tunnel bioassays supported previous independent findings, with more of a NL population landing on the yellow LED lamp (588 nm) than the blue (470 nm) (p = 0.022), and a not-statistically significant trend observed in a DE population landing more on blue compared to yellow (p = 0.104). To account for potential original host rearing influences, both populations were subsequently established on bean for ~20 weeks, then yellow chrysanthemum for 4–8 and 12–14 weeks and tested in wind tunnel choice bioassays. Laboratory of origin, irrespective of the host plant rearing regime, remained a significant effect (p < 0.001), with 65% of the NL WFT landing on yellow compared to blue (35%), while 66% of the DE WFT landed on blue compared to yellow (34%). There was also a significant host plant effect (p < 0.001), with increased response to yellow independent of laboratory of origin after rearing on chrysanthemum for 12–14 weeks. Results suggest that differing responses of WFT populations to colour is, in this case, independent of the experimental situation. Long-term separate isolation from the wild cannot be excluded as a cause, and the implications of this for optimising the trap colour is discussed

Macroevolutionary Patterns in the Aphidini Aphids (Hemiptera: Aphididae): Diversification, Host Association, and Biogeographic Origins

, the most diverse genus in the family. We used a combined dataset of one nuclear and four mitochondrial DNA regions. A molecular dating approach, calibrated with fossil records, was used to estimate divergence times of these taxa.Most generic divergences in Aphidini occurred in the Middle Tertiary, and species-level divergences occurred between the Middle and Late Tertiary. The ancestral state of host use for Aphidini was equivocal with respect to three states: monoecy on trees, heteroecy, and monoecy on grasses. The ancestral state of Rhopalosiphina likely included both heteroecy and monoecy, whereas that of Aphidina was most likely monoecy. The divergence times of aphid lineages at the generic or subgeneric levels are close to those of their primary hosts. The species-level divergences in aphids are consistent with the diversification of the secondary hosts, as a few examples suggest. The biogeographic origin of Aphidini as a whole was equivocal, but the major lineages within Aphidina likely separated into Nearctic, Western Palearctic, and Eastern Palearctic regions.Most generic divergences in Aphidini occurred in the Middle Tertiary when primary hosts, mainly in the Rosaceae, were diverging, whereas species-level divergences were contemporaneous with diversification of the secondary hosts such as Poaceae in the Middle to Late Tertiary. Our results suggest that evolution of host alternation within Aphidini may have occurred during the Middle Tertiary (Oligocene) when the secondary hosts emerged