Targeted therapy for breast cancer prevention.

With a better understanding of the etiology of breast cancer, molecularly targeted drugs have been developed and are being testing for the treatment and prevention of breast cancer. Targeted drugs that inhibit the estrogen receptor (ER) or estrogen-activated pathways include the selective ER modulators (tamoxifen, raloxifene, and lasofoxifene) and aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) have been tested in preclinical and clinical studies. Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer and promising results of AIs in breast cancer trials, suggest that AIs might be even more effective in the prevention of ER-positive breast cancer. However, these agents only prevent ER-positive breast cancer. Therefore, current research is focused on identifying preventive therapies for other forms of breast cancer such as human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC, breast cancer that does express ER, progesterone receptor, or HER2). HER2-positive breast cancers are currently treated with anti-HER2 therapies including trastuzumab and lapatinib, and preclinical and clinical studies are now being conducted to test these drugs for the prevention of HER2-positive breast cancers. Several promising agents currently being tested in cancer prevention trials for the prevention of TNBC include poly(ADP-ribose) polymerase inhibitors, vitamin D, and rexinoids, both of which activate nuclear hormone receptors (the vitamin D and retinoid X receptors). This review discusses currently used breast cancer preventive drugs, and describes the progress of research striving to identify and develop more effective preventive agents for all forms of breast cancer

Numerical simulations on the motion of atoms travelling through a standing-wave light field

The motion of metastable helium atoms travelling through a standing light wave is investigated with a semi-classical numerical model. The results of a calculation including the velocity dependence of the dipole force are compared with those of the commonly used approach, which assumes a conservative dipole force. The comparison is made for two atom guiding regimes that can be used for the production of nanostructure arrays; a low power regime, where the atoms are focused in a standing wave by the dipole force, and a higher power regime, in which the atoms channel along the potential minima of the light field. In the low power regime the differences between the two models are negligible and both models show that, for lithography purposes, pattern widths of 150 nm can be achieved. In the high power channelling regime the conservative force model, predicting 100 nm features, is shown to break down. The model that incorporates velocity dependence, resulting in a structure size of 40 nm, remains valid, as demonstrated by a comparison with quantum Monte-Carlo wavefunction calculations.Comment: 9 pages, 4 figure

Influence of the lattice topography on a three-dimensional, controllable Brownian motor

We study the influence of the lattice topography and the coupling between motion in different directions, for a three-dimensional Brownian motor based on cold atoms in a double optical lattice. Due to controllable relative spatial phases between the lattices, our Brownian motor can induce drifts in arbitrary directions. Since the lattices couple the different directions, the relation between the phase shifts and the directionality of the induced drift is non trivial. Here is therefore this relation investigated experimentally by systematically varying the relative spatial phase in two dimensions, while monitoring the vertically induced drift and the temperature. A relative spatial phase range of 2pi x 2pi is covered. We show that a drift, controllable both in speed and direction, can be achieved, by varying the phase both parallel and perpendicular to the direction of the measured induced drift. The experimental results are qualitatively reproduced by numerical simulations of a simplified, classical model of the system

Covariant quantum measurements may not be optimal

Quantum particles, such as spins, can be used for communicating spatial directions to observers who share no common coordinate frame. We show that if the emitter's signals are the orbit of a group, then the optimal detection method may not be a covariant measurement (contrary to widespread belief). It may be advantageous for the receiver to use a different group and an indirect estimation method: first, an ordinary measurement supplies redundant numerical parameters; the latter are then used for a nonlinear optimal identification of the signal.Comment: minor corrections, to appear in J. Mod. Opt. (proc. of Gdansk conf.

Effects of low level military training flights on wading bird colonies in Florida

During 1983 and 1984 the effect of low level military training flights on the establishment. size and reproductive success of wading bird colonies was studied in Florida. Based on the indirect evidence of colony distributions and turnover rates in relation to military areas (training routes designated to 500 feet or less above ground level and military operations areas). there was no demonstrated effect of military activity on wading bird colony establishment or size on a statewide basis. Colony distributions were random with respect to military areas and turnover rates were within 2% when military and non-military areas were compared. Colony distributions and turnover rates, however. were related to the amount and type.Les tuer-tne or freshwater) of wetland. respectively. During two breeding seasons the behavioral responses and reproductive success of selected species were monitored in a non-habituated treatment colony (military overflights) and a control colony (no overflights). Breeding wading birds responded to F-16 overflights at 420 knots indicated airspeed. 82-84% maximum rpm. 500 feet above ground level and sound levels ranging from 55-100 dBA by exhibiting no response. looking up or changing position (usually to an alert posture): no productivity limiting responses were observed. High-nesting Great Egrets responded more than other species, nestling Great Egrets and Cattle Egrets responded significantly (r <.05) more intensely than adults of their respective species, and adults responded less during incubation and late chick-rearing than at other times. In addition, no differences in adult attendance, aggressive interactions or chick feeding rates were observed to result from F-16 overflights. No evidence of habituation to overflights was noted. Humans entering the colony or airboats approaching the colony vicinity elicited the most severe responses (flushing and panic flights) observed at both sites. Since relatively little coastal military activity occurs at low levels ( ~500 ft) and only one Brown Pelican colony (5-6% of the breeding population) was located in such an area, the reproductive success of five, more lIexposedll study species (Great Egrets, Snowy Egrets, Tricolored Herons, Little Blue Herons, Cattle Egrets) nesting in interior freshwater colonies was studied. Reproductive activity including such factors as nest success, nestling survival, nestling mortality, and nesting chronology was independent of F-16 overflights but related to ecological factors including colony location, colony characteristics and climatology. The responses to and effects of F-16 overflights, as reported here, should not be considered representative of military aircraft at lower altitudes or greater noise levels. (194 pages

Antibiotics with Interleukin-15 inhibition reduces joint inflammation and bone erosions but not cartilage destruction in Staphylococcus aureus-induced arthritis

Background: Staphylococcus aureus-induced arthritis causes rapid joint destruction, often leading to disabling joint damage despite antibiotics. We have previously shown that IL-15 inhibition without antibiotics is beneficial in S. aureus-induced arthritis. We therefore hypothesized that inhibition of IL-15, in combination with antibiotics, might represent a useful therapy that would both reduce inflammation and joint destruction, but preserve the host's ability to clear the infection. Methods: Female wildtype C57BL/6 mice were intravenously inoculated with the TSST-1-producing LS-1 strain of S. aureus with 0.8x108 S. aureus LS-1/mouse. Three days later the treatment was started consisting of cloxacillin followed by flucloxacillin, together with either anti-IL-15 antibodies (aIL-15ab) or control antibodies. Outcomes included survival, weight change, bacterial clearance, and joint damage. Results: The addition of aIL-15ab to antibiotics in S. aureus-induced arthritis reduced synovitis and bone erosions compared to controls. The number of bone-resorbing osteoclasts in the joints was reduced, whereas cartilage destruction was not significantly altered. Importantly, the combination therapy did not adversely affect the clinical outcome of S. aureus-induced arthritis, such as survival, weight change or compromise the host's ability to clear the infection. Conclusions: As the clinical outcome of S. aureus-induced arthritis was not affected, the addition of aIL-15ab to antibiotics ought to be safe. Taken together, the combination of aIL-15ab and antibiotics is a beneficial, but not optimal, treatment of S. aureus-induced arthritis as it reduces synovitis and bone erosions but has a limited effect on cartilage destruction

Testing the limits of particle acceleration in cygnus OB2 with HAWC

Star forming regions (SFRs) have been postulated as possible sources of cosmic rays (CRs) in our galaxy. One example of a gamma-ray source associated with an SFR is the Fermi-LAT cocoon, an extended region of gamma-ray emission in the Cygnus X region and attributed to a possible superbubble with freshly accelerated CRs. Because the emission region is surrounded by ionization fronts, it has been named the Cygnus cocoon. CRs in the cocoon could have originated in the OB2 association and been accelerated at the interaction sites of stellar winds of massive O type stars. So far, there is no clear association at TeV energies. Spectral and morphological studies of TeV gamma-ray emission detected by the High Altitude Water Cherenkov (HAWC) observatory at the 2HWC J2031+415 region reveal that the spectral energy distribution of the cocoon extends from GeV to at least tens of TeV. Using HAWC data, we are able to study the acceleration of particles to highest energies in the Cygnus OB2 SFR