The theory of quantum levitators

We develop a unified theory for clocks and gravimeters using the interferences of multiple atomic waves put in levitation by traveling light pulses. Inspired by optical methods, we exhibit a propagation invariant, which enables to derive analytically the wave function of the sample scattering on the light pulse sequence. A complete characterization of the device sensitivity with respect to frequency or to acceleration measurements is obtained. These results agree with previous numerical simulations and confirm the conjecture of sensitivity improvement through multiple atomic wave interferences. A realistic experimental implementation for such clock architecture is discussed.Comment: 11 pages, 6 Figures. Minor typos corrected. Final versio

Gravitational Redshift, Equivalence Principle, and Matter Waves

We review matter wave and clock comparison tests of the gravitational redshift. To elucidate their relationship to tests of the universality of free fall (UFF), we define scenarios wherein redshift violations are coupled to violations of UFF ("type II"), or independent of UFF violations ("type III"), respectively. Clock comparisons and atom interferometers are sensitive to similar effects in type II and precisely the same effects in type III scenarios, although type III violations remain poorly constrained. Finally, we describe the "Geodesic Explorer," a conceptual spaceborne atom interferometer that will test the gravitational redshift with an accuracy 5 orders of magnitude better than current terrestrial redshift experiments for type II scenarios and 12 orders of magnitude better for type III.Comment: Work in progress. 11 page

Is it possible to detect gravitational waves with atom interferometers?

We investigate the possibility to use atom interferometers to detect gravitational waves. We discuss the interaction of gravitational waves with an atom interferometer and analyze possible schemes

Complete intersections: Moduli, Torelli, and good reduction

We study the arithmetic of complete intersections in projective space over number fields. Our main results include arithmetic Torelli theorems and versions of the Shafarevich conjecture, as proved for curves and abelian varieties by Faltings. For example, we prove an analogue of the Shafarevich conjecture for cubic and quartic threefolds and intersections of two quadrics.Comment: 37 pages. Typo's fixed. Expanded Section 2.

Cellular pharmacology of multi- and duplex drugsconsisting of ethynylcytidine and 5-fluoro-2′-deoxyuridine

Prodrugs can have the advantage over parent drugs in increased activation and cellular uptake. The multidrug ETC-L-FdUrd and the duplex drug ETC-FdUrd are composed of two different monophosphate-nucleosides, 5-fluoro-2′deoxyuridine (FdUrd) and ethynylcytidine (ETC), coupled via a glycerolipid or phosphodiester, respectively. The aim of the study was to determine cytotoxicity levels and mode of drug cleavage. Moreover, we determined whether a liposomal formulation of ETC-L-FdUrd would improve cytotoxic activity and/or cleavage. Drug effects/cleavage were studied with standard radioactivity assays, HPLC and LC-MS/MS in FM3A/0 mammary cancer cells and their FdUrd resistant variants FM3A/TK−. ETC-FdUrd was active (IC50 of 2.2 and 79 nM) in FM3A/0 and TK− cells, respectively. ETC-L-FdUrd was less active (IC50: 7 nM in FM3A/0 vs 4500 nM in FM3A/TK−). Although the liposomal formulation was less active than ETC-L-FdUrd in FM3A/0 cells (IC50:19.3 nM), resistance due to thymidine kinase (TK) deficiency was greatly reduced. The prodrugs inhibited thymidylate synthase (TS) in FM3A/0 cells (80–90%), but to a lower extent in FM3A/TK− (10–50%). FdUMP was hardly detected in FM3A/TK− cells. Inhibition of the transporters and nucleotidases/phosphatases resulted in a reduction of cytotoxicity of ETC-FdUrd, indicating that this drug was cleaved outside the cells to the monophosphates, which was verified by the presence of FdUrd and ETC in the medium. ETC-L-FdUrd and the liposomal formulation were neither affected by transporter nor nucleotidase/phosphatase inhibition, indicating circumvention of active transporters. In vivo, ETC-FdUrd and ETC-L-FdURd were orally active. ETC nucleotides accumulated in both tumor and liver tissues. These formulations seem to be effective when a lipophilic linker is used combined with a liposomal formulation

Transient Increase in Cyclic AMP Localized to Macrophage Phagosomes

Cyclic AMP (cAMP) regulates many biological processes and cellular functions. The importance of spatially localized intracellular gradients of cAMP is increasingly appreciated. Previous work in macrophages has shown that cAMP is produced during phagocytosis and that elevated cAMP levels suppress host defense functions, including generation of proinflammatory mediators, phagocytosis and killing. However, the spatial and kinetic characteristics of cAMP generation in phagocytosing macrophages have yet to be examined. Using a Förster resonance energy transfer (FRET)-based cAMP biosensor, we measured the generation of cAMP in live macrophages. We detected no difference in bulk intracellular cAMP levels between resting cells and cells actively phagocytosing IgG-opsonized particles. However, analysis with the biosensor revealed a rapid decrease in FRET signal corresponding to a transient burst of cAMP production localized to the forming phagosome. cAMP levels returned to baseline after the particle was internalized. These studies indicate that localized increases in cAMP accompany phagosome formation and provide a framework for a more complete understanding of how cAMP regulates macrophage host defense functions

Changes in the status of p53 affect drug sensitivity to thymidylate synthase (TS) inhibitors by altering TS levels

Colorectal cancer (CRC) resistance to fluoropyrimidines and other inhibitors of thymidylate synthase (TS) is a serious clinical problem often associated with increased intracellular levels of TS. Since the tumour suppressor gene p53, which is mutated in 50% of CRC, regulates the expression of several genes, it may modulate TS activity, and changes in the status of p53 might be responsible for chemoresistance. Therefore, this study was aimed to investigate TS levels and sensitivity to TS inhibitors in wild-type (wt) and mutant (mt) p53 CRC cells, Lovo and WiDr, respectively, transfected with mt and wt p53. Lovo 175X2 cells (transfected with mt p53) were more resistant to 5-fluorouracil (5-FU; 2-fold), nolatrexed (3-fold), raltitrexed (3-fold) and pemetrexed (10-fold) in comparison with the wt p53 parental cells Lovo 92. Resistance was associated with an increase in TS protein expression and catalytic activity, which might be caused by the loss of the inhibitory effect on the activity of TS promoter or by the lack of TS mRNA degradation, as suggested by the reversal of TS expression to the levels of Lovo 92 cells by adding actinomycin. In contrast, Lovo li cells, characterized by functionally inactive p53, were 3-13-fold more sensitive to nolatrexed, raltitrexed and pemetrexed, and had a lower TS mRNA, protein expression and catalytic activity than Lovo 92. However, MDM-2 expression was significantly higher in Lovo li, while no significant differences were observed in Lovo 175X2 cells with respect to Lovo 92. Finally, mt p53 WiDr transfected with wt p53 were not significantly different from mt p53 WiDr cells with respect to sensitivity to TS inhibitors or TS levels. Altogether, these results indicate that changes in the status of p53, can differently alter sensitivity to TS inhibitors by affecting TS levels, depending on activity or cell line, and might explain the lack of clear correlation between mutations in p53 and clinical outcome after chemotherapy with TS inhibitors

Magnetic neutron scattering in hole doped cuprate superconductors

A review is presented of the static and dynamic magnetic properties of hole-doped cuprate superconductors measured with neutron scattering. A wide variety of experiments are described with emphasis on the monolayer La_{2-x}(Sr,Ba)_{x}CuO_{4} and bilayer YBa_{2}Cu_{3}O_{6+x} cuprates. At zero hole doping, both classes of materials are antiferromagnetic insulators with large superexchange constants of J > 100 meV. For increasing hole doping, the cuprates become superconducting at a critical hole concentration of x_{c}=0.055. The development of new instrumentation at neutron beam sources coupled with the improvement in materials has lead to a better understanding of these materials and the underlying spin dynamics over a broad range of hole dopings. We will describe how the spin dispersion changes across the insulating to superconducting boundary as well as the static magnetic properties which are directly coupled with the superconductivity. Experiments directly probing the competing magnetic and superconducting order parameters involving magnetic fields, impurity doping, and structural order will be examined. Correlations between superconductivity and magnetism will also be discussed.Comment: 14 pages, 18 figures. To be published in Journal of the Physical Society of Japa

A Study of Time-Dependent CP-Violating Asymmetries and Flavor Oscillations in Neutral B Decays at the Upsilon(4S)

We present a measurement of time-dependent CP-violating asymmetries in neutral B meson decays collected with the BABAR detector at the PEP-II asymmetric-energy B Factory at the Stanford Linear Accelerator Center. The data sample consists of 29.7 ${\rm fb}^{-1}$ recorded at the $\Upsilon(4S)$ resonance and 3.9 ${\rm fb}^{-1}$ off-resonance. One of the neutral B mesons, which are produced in pairs at the $\Upsilon(4S)$, is fully reconstructed in the CP decay modes $J/\psi K^0_S$, $\psi(2S) K^0_S$, $\chi_{c1} K^0_S$, $J/\psi K^{*0}$ ($K^{*0}\to K^0_S\pi^0$) and $J/\psi K^0_L$, or in flavor-eigenstate modes involving $D^{(*)}\pi/\rho/a_1$ and $J/\psi K^{*0}$ ($K^{*0}\to K^+\pi^-$). The flavor of the other neutral B meson is tagged at the time of its decay, mainly with the charge of identified leptons and kaons. The proper time elapsed between the decays is determined by measuring the distance between the decay vertices. A maximum-likelihood fit to this flavor eigenstate sample finds $\Delta m_d = 0.516\pm 0.016 {\rm (stat)} \pm 0.010 {\rm (syst)} {\rm ps}^{-1}$. The value of the asymmetry amplitude $\sin2\beta$ is determined from a simultaneous maximum-likelihood fit to the time-difference distribution of the flavor-eigenstate sample and about 642 tagged $B^0$ decays in the CP-eigenstate modes. We find $\sin2\beta=0.59\pm 0.14 {\rm (stat)} \pm 0.05 {\rm (syst)}$, demonstrating that CP violation exists in the neutral B meson system. (abridged)Comment: 58 pages, 35 figures, submitted to Physical Review