Improving the adoption of household health products: a sales experiment with chlorine tablets

We test a door-to-door marketing intervention aimed to increase use of a targeted health product among poor households. Specifically, we examine three treatments in which this good–chlorine tablets for drinking water purification–is: (1) sold alone, (2) sold alongside a familiar and cheaper side good that is priced at its retail value, and (3) sold alongside the same side good that is priced on a promotional offer. The side good when sold at retail price is intended to be an “opt-out” good to reduce the marketing pressure, which should in turn reduce the amount of products sold that go unused. When the side good is sold on promotion, however, we hypothesize that it reintroduces marketing pressure due to the “gift” aspect of the promotion. Consistent with this hypothesis, we find that chlorine use is nearly double in the second condition compared to the other two conditions. Our results suggest that household valuation of a new product is shaped by both the presence and the price of a side good due to marketing pressure

Ultra-Low Noise Microwave Extraction from Fiber-Based Optical Frequency Comb

In this letter, we report on all-optical fiber approach to the generation of ultra-low noise microwave signals. We make use of two erbium fiber mode-locked lasers phase locked to a common ultra-stable laser source to generate an 11.55 GHz signal with an unprecedented relative phase noise of -111 dBc/Hz at 1 Hz from the carrier.The residual frequency instability of the microwave signals derived from the two optical frequency combs is below 2.3 10^(-16) at 1s and about 4 10^(-19) at 6.5 10^(4)s (in 5 Hz bandwidth, three days continuous operation).Comment: 12 pages, 3 figure

Two-photon imaging of a magneto-optical trap in a microfabricated cell for cold atom sensors

International audienceWe have produced a sample of laser-cooled atoms in a micro-fabricated alkali vapor cell using a grating MOT to direct the beams. We show that by detecting the blue fluorescence resulting from a two-photon cascade transition, we improve the rejection of cooling light scattered from the grating

Reduction of helium permeation in microfabricated cells using aluminosilicate glass substrates and Al2_2O3_3 coatings

The stability and accuracy of atomic devices can be degraded by the evolution of their cell inner atmosphere. Hence, the undesired entrance or leakage of background or buffer gas, respectively, that can permeate through the cell walls, should be slowed down. In this work, we investigate helium permeation in microfabricated alkali vapor cells filled with He and whose windows are made of borosilicate glass (BSG) or aluminosilicate glass (ASG). The permeation is then derived from routine measurements of the pressure-shifted hyperfine transition frequency of an atomic clock. We first confirm that ASG reduces He permeation rate by more than two orders of magnitude, in comparison with BSG. In addition, we demonstrate that Al$_2$O$_3$ thin-film coatings, known to avoid alkali consumption in vapor cells, can also significantly reduce He permeation. The permeation through BSG is thereby reduced by a factor 110 whereas the one through ASG is decreased by a factor up to 5.8 compared to uncoated substrates. These results may contribute to the development of miniaturized atomic clocks and sensors with improved long-term stability or sensitivity.Comment: 7 pages, 5 figure

Identification of chemokine receptors as potential modulators of endocrine resistance in oestrogen receptor–positive breast cancers

Introduction Endocrine therapies target oestrogenic stimulation of breast cancer (BC) growth, but resistance remains problematic. Our aims in this study were (1) to identify genes most strongly associated with resistance to endocrine therapy by intersecting global gene transcription data from patients treated presurgically with the aromatase inhibitor anastrazole with those from MCF7 cells adapted to long-term oestrogen deprivation (LTED) (2) to assess the clinical value of selected genes in public clinical data sets and (3) to determine the impact of targeting these genes with novel agents. Methods Gene expression and Ki67 data were available from 69 postmenopausal women with oestrogen receptor–positive (ER+) early BC, at baseline and 2 weeks after anastrazole treatment, and from cell lines adapted to LTED. The functional consequences of target genes on proliferation, ER-mediated transcription and downstream cell signalling were assessed. Results By intersecting genes predictive of a poor change in Ki67 with those upregulated in LTED cells, we identified 32 genes strongly correlated with poor antiproliferative response that were associated with inflammation and/or immunity. In a panel of LTED cell lines, C-X-C chemokine receptor type 7 (CXCR7) and CXCR4 were upregulated compared to their wild types (wt), and CXCR7, but not CXCR4, was associated with reduced relapse-free survival in patients with ER+ BC. The CXCR4 small interfering RNA variant (siCXCR4) had no specific effect on the proliferation of wt-SUM44, wt-MCF7 and their LTED derivatives. In contrast, siCXCR7, as well as CCX733, a CXCR7 antagonist, specifically suppressed the proliferation of MCF7-LTED cells. siCXCR7 suppressed proteins associated with G1/S transition and inhibited ER transactivation in MCF7-LTED, but not wt-MCF7, by impeding association between ER and proline-, glutamic acid– and leucine-rich protein 1, an ER coactivator. Conclusions These data highlight CXCR7 as a potential therapeutic target warranting clinical investigation in endocrine-resistant BC

Compact E-Cash and Simulatable VRFs Revisited

Abstract. Efficient non-interactive zero-knowledge proofs are a powerful tool for solving many cryptographic problems. We apply the recent Groth-Sahai (GS) proof system for pairing product equations (Eurocrypt 2008) to two related cryptographic problems: compact e-cash (Eurocrypt 2005) and simulatable verifiable random functions (CRYPTO 2007). We present the first efficient compact e-cash scheme that does not rely on a random oracle. To this end we construct efficient GS proofs for signature possession, pseudo randomness and set membership. The GS proofs for pseudorandom functions give rise to a much cleaner and substantially faster construction of simulatable verifiable random functions (sVRF) under a weaker number theoretic assumption. We obtain the first efficient fully simulatable sVRF with a polynomial sized output domain (in the security parameter).

Antikinetoplastid SAR study in 3-nitroimidazopyridine series: identification of a novel non-genotoxic and potent anti-T. b. brucei hit-compound with improved pharmacokinetic properties

To study the antikinetoplastid 3-nitroimidazo[1,2-a]pyridine pharmacophore, a structure-activity relationship study was conducted through the synthesis of 26 original derivatives and their in vitro evaluation on both Leishmania spp and Trypanosoma brucei brucei. This SAR study showed that the antitrypanosomal pharmacophore was less restrictive than the antileishmanial one and highlighted positions 2, 6 and 8 of the imidazopyridine ring as key modulation points. None of the synthesized compounds allowed improvement in antileishmanial activity, compared to previous hit molecules in the series. Nevertheless, compound 8, the best antitrypanosomal molecule in this series (EC50 = 17 nM, SI = 2650 & E° = -0.6 V), was not only more active than all reference drugs and previous hit molecules in the series but also displayed improved aqueous solubility and better in vitro pharmacokinetic characteristics: good microsomal stability (T1/2 > 40 min), moderate albumin binding (77%) and moderate permeability across the blood brain barrier according to a PAMPA assay. Moreover, both micronucleus and comet assays showed that nitroaromatic molecule 8 was not genotoxic in vitro. It was evidenced that bioactivation of molecule 8 was operated by T. b. brucei type 1 nitroreductase, in the same manner as fexinidazole. Finally, a mouse pharmacokinetic study showed that 8 displayed good systemic exposure after both single and repeated oral administrations at 100 mg/kg (NOAEL) and satisfying plasmatic half-life (T1/2 = 7.7 h). Thus, molecule 8 appears as a good candidate for initiating a hit to lead drug discovery program