Symmetrical α,β-unsaturated ketones, analogs of curcumin, show powerful in vitro anti-cancer and anti-angiogenic properties, one of which likewise reduces the volume of human breast tumors grown in ...female athymic nude mice. In vitro activities have been captured in a predictive 3D-QSAR model.
A series of novel curcumin analogs were synthesized and screened for anti-cancer and anti-angiogenesis activities at Emory University and at the National Cancer Institute (NCI). These compounds are symmetrical α,β-unsaturated and saturated ketones. The majority of the analogs demonstrated a moderate degree of anti-cancer activity. Compounds
10,
11, and
14 exhibited a high degree of cytotoxicity in the NCI in vitro anti-cancer cell line screen. In addition, this screen revealed that these compounds inhibit tumor cell growth with a higher potency than the commonly used chemotherapeutic drug, cisplatin. In independent in vitro screens conducted at Emory, the same compounds plus
4,
5,
8,
9, and
13 exhibited a high degree of cytotoxicity to tumor cells. Analogs that were effective in the anti-cancer screens were also effective in in vitro anti-angiogenesis assays. Compounds
4,
9,
11, and
14 were most effective in the anti-angiogenesis assays run at Emory. In the assays conducted by the NCI, compound
14 was almost as potent as the anti-angiogenic drug TNP-470, which has undergone clinical trials. Based on the favorable in vitro anti-cancer and anti-angiogenesis results with
14, further in vivo tests were conducted. This compound effectively reduced the size of human breast tumors grown in female athymic nude mice and showed little toxicity. This data, coupled with the remarkable in vitro data, suggests that compound
14 may potentially be an effective chemotherapeutic agent. As a follow-up, a 3D quantitative structure relationship based on
14 has been developed. It shows a cross-validated
r
2(
q
2)=0.83 and a predictive
r
2(
p
2)=0.71. COMPARE analysis suggests the compound to be a possible RNA/DNA antimetabolite, but also implies that the compound's cytotoxicity may arise from a presently unknown mechanism.
Mental imagery may represent a weaker form of perception and, thus, mental images may be more ambiguous than visual percepts. If correct, the acquisition of fear would be less specific for imagined ...fears in comparison to perceptual fears, perhaps facilitating broader fear generalization. To test this idea, a two-day differential fear conditioning experiment (N = 98) was conducted. On day one, two groups of participants underwent differential fear conditioning such that a specific Gabor patch orientation (CS+) was paired with mild shocks (US) while a second Gabor patch of orthogonal orientation (CS-) was never paired with shock. Critically, one group imagined the Gabor patches and the other group was visually presented the Gabor patches. Next, both groups were presented visual Gabor patches of similar orientations (GCS) to the CS+. On day two, to assess the persistence of imagined fear, participants returned to the lab and were tested on the GCS devoid of shock. For day one, in contrast to our primary hypothesis, both self-report and skin conductance response measures did not show a significant interaction between the GCS and groups. On day two, both measures demonstrated a persistence of imagined fear, without US delivery. Taken together, rather than demonstrating an overgeneralization effect, the results from this study suggest that imagery-based fear conditioning generalizes to a similar extent as perceptually acquired fear conditioning. Further, the persistence of imagery-based fear may have unique extinction qualities in comparison to perceptual-based fear.
•On day one, the generalization of a fear created in one’s imagination was tested.•On day two, after a night of sleep, the persistence of a fear created in one’s imagination was tested.•An imagery-based fear appears to spread to perceptually similar stimuli, consistent with visual-based fear generalization.•After a night of sleep, an imagery-based fear persists, even without continued aversive reinforcement.
Enterococci are ubiquitous lactic acid bacteria commonly associated with the human digestive tract as commensal organisms. Additionally, these organisms have a long history of use in foods improving ...flavor as well as providing protective mechanisms as either a probiotic or antimicrobial additive. However,
Enterococcus faecalis accounts for up to 10% of all nosocomial infections of the bloodstream, wounds, urinary tract and heart. Knowledge about the regulation of virulence factors is limited and the involvement of environmental signals contributing to
E. faecalis pathogenicity is poorly documented. In this study, two clinical
E. faecalis isolates, TMW 2.63 and OG1RF, as well as one food isolate, TMW 2.629, were subjected to six sub-lethal food- and host-related stresses including 6.8% NaCl, 200 ppm nitrite, 51 °C, 80 MPa, pH 4.1 and 0.08% bile salts (cholic acid:chenodeoxycholic acid 1:1), respectively, reducing their growth rate to 10%. Relative gene expression of 15 stress and virulence-associated genes including
dnaK,
groEL,
ctsR,
clpPBCEX,
gls24,
efaAfs,
ace,
fsrB,
gelE,
sprE and
cylB, was quantified by using real time PCR and Lightcycler
® technology (reference conditions: BHI broth, 37 °C, pH = 7.4). Apart from strain-dependent differences, sub-lethal environmental stress was capable of provoking significant alterations in the expression of virulence-associated genes in
E. faecalis from clinical as well as food origins of isolation. These results help to avoid preconditioning enterococci in food production processes and to understand the complex mechanisms in
E. faecalis' switch to pathogenicity.
The fabrication of micro-optical elements by electron-beam lithography and dry etching technique using a top conductive coating is presented. This conductive layer prevents the occurrence of charging ...effects during electron-beam exposure. Several different structures, mainly for use in micro-optics using various resist types, were realised in dielectric substrates. The use of top conductive coatings proved to be practical, reliable and simple.
The fabrication of three-dimensional microstructure elements by electron-beam lithography and dry etching technique is shown for the example of typical three-dimensional optical structures (Echelette ...gratings, computer generated diffractive optical elements and Fresnel zone lenses). Several different structures, mainly for use in micro-optics with feature sizes in the micrometer range and below were realised. The utilisation of electron-beam lithography thereby proved to be extremely flexible and precise.
The paper reports on the industrial application of SystemC AMS for semi-symbolic analysis. As a case study we analyze the accuracy of a fuel consumption measurement system. As results, two approaches ...are presented that make formal and symbolic methods more accessible for industrial practice: (1) integration of symbolic simulation into SystemC AMS, which makes the application similar to the established concrete simulation, and (2) uncertainty tables to further simplify the remaining symbolic modeling of inputs and constraints.
In this work various designs of crystal-based Bragg–Fresnel elements are analyzed from the viewpoint of increasing a radiation flux collected in the focus and technological possibilities for their ...fabrication. To increase the radiation flux collected in the focus the creation of additional zones contributing to the first diffraction order is proposed, which terminate when their width reaches the technological limit of the used procedure. Further flux increase can be achieved by creating zones contributing to the third diffraction order.
Silicon dioxide etching technology for structuring planar optical components of some micrometers structure depth has been developed using an electron cyclotron resonance (ECR) plasma etcher. The ...optimum conditions for silicon dioxide etching are obtained in terms of etch rate, selectivity, and low radiation damage to the etched surface by fully utilizing such advantages of the ECR plasma etcher as high plasma density, low pressure operation, and independent control of ion energy and plasma discharge. A highly selective etching process has been developed enabling the structuring of high quality SiO
2 components as e.g. arrayed-waveguide gratings and Fresnel zone lenses at etching rates of some hundreds of nanometers per minute.
A novel concept has been developed for overlaying a power-splitting passive optical network (PON) in one wavelength band with a wavelength-division-multiplexed (WDM) PON in another wavelength band. ...An eight-channel device fabricated in silica technique shows an insertion loss of 3.5 dB and a crosstalk of -23 dB for the WDM channels around 1.55 μm wavelength. The 1 to 8 splitting function at 1.50 μm wavelength has an additional penalty of -1 dB and a uniformity of /spl plusmn/0.5 dB.
We present a measurement of the longitudinal spin asymmetry A(||) in photoproduction of pairs of hadrons with high transverse momentum p(T). Data were accumulated by the HERMES experiment using a ...27.5 GeV polarized positron beam and a polarized hydrogen target internal to the HERA storage ring. For h(+)h(-) pairs with p(h(1))(T)>1.5 GeV/c and p(h(2))(T)>1.0 GeV/c, the measured asymmetry is A(||) = -0. 28+/-0.12(stat)+/-0.02(syst). This negative value is in contrast to the positive asymmetries typically measured in deep inelastic scattering from protons, and is interpreted to arise from a positive gluon polarization.
PDF