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

White-faced Darter distribution is associated with coniferous forests in Great Britain

Abstract 1) Understanding of dragonfly distributions is often geographically comprehensive but less so in ecological terms. 2) White-faced darter (Leucorhinnia dubia) is a lowland peatbog specialist dragonfly which has experienced population declines in Great Britain. White-faced darter are thought to rely on peat-rich pool complexes within woodland but this has not yet been empirically tested. 3) We used dragonfly recording data collected by volunteers of the British Dragonfly Society from 2005 to 2018 to model habitat preference for white-faced darter using species distribution models across Great Britain and, with a more detailed landcover dataset, specifically in the North of Scotland. 4) Across the whole of Great Britain our models used the proportion of coniferous forest within 1km as the most important predictor of habitat suitability but were not able to predict all current populations in England. 5) In the North of Scotland our models were more successful and suggest that habitats characterised by native coniferous forest and areas high potential evapotranspiration represent the most suitable habitat for white-faced darter. 6) We recommend that future white-faced darter monitoring should be expanded to include areas currently poorly surveyed but with high suitability in the North of Scotland. 7) Our results also suggest that white-faced darter management should concentrate on maintaining Sphagnum rich pool complexes and the maintenance and restoration of native forests in which these pool complexes occur

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

Additive Combinatorics and Discrete Logarithm Based Range Protocols

We show how to express an arbitrary integer interval $I = [0, H]$ as a sumset $I = \sum_{i=1}^\ell G_i * [0, u - 1] + [0, H']$ of smaller integer intervals for some small values $\ell$, $u$, and $H' < u - 1$, where $b * A = \{b a : a \in A\}$ and $A + B = \{a + b : a \in A \wedge b \in B\}$. We show how to derive such expression of $I$ as a sumset for any value of $1 < u < H$, and in particular, how the coefficients $G_i$ can be found by using a nontrivial but efficient algorithm. This result may be interesting by itself in the context of additive combinatorics. Given the sumset-representation of $I$, we show how to decrease both the communication complexity and the computational complexity of the recent pairing-based range proof of Camenisch, Chaabouni and shelat from ASIACRYPT 2008 by a factor of $2$. Our results are important in applications like e-voting where a voting server has to verify thousands of proofs of e-vote correctness per hour. Therefore, our new result in additive combinatorics has direct relevance in practice

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).

Non-Interactive Zero-Knowledge Proofs for Composite Statements

The two most common ways to design non-interactive zero-knowledge (NIZK) proofs are based on Sigma protocols and QAP-based SNARKs. The former is highly efficient for proving algebraic statements while the latter is superior for arithmetic representations. Motivated by applications such as privacy-preserving credentials and privacy-preserving audits in cryptocurrencies, we study the design of NIZKs for composite statements that compose algebraic and arithmetic statements in arbitrary ways. Specifically, we provide a framework for proving statements that consist of ANDs, ORs and function compositions of a mix of algebraic and arithmetic components. This allows us to explore the full spectrum of trade-offs between proof size, prover cost, and CRS size/generation cost. This leads to proofs for statements of the form: knowledge of $x$ such that $SHA(g^x)=y$ for some public $y$ where the prover\u27s work is 500 times fewer exponentiations compared to a QAP-based SNARK at the cost of increasing the proof size to 2404 group and field elements. In application to anonymous credentials, our techniques result in 8 times fewer exponentiations for the prover at the cost of increasing the proof size to 298 elements

SWiM: Secure Wildcard Pattern Matching From OT Extension

Suppose a server holds a long text string and a receiver holds a short pattern string. Secure pattern matching allows the receiver to learn the locations in the long text where the pattern appears, while leaking nothing else to either party besides the length of their inputs. In this work we consider secure wildcard pattern matching WPM, where the receiver\u27s pattern is allowed to contain wildcards that match to any character. We present SWiM, a simple and fast protocol for WPM that is heavily based on oblivious transfer (OT) extension. As such, the protocol requires only a small constant number of public-key operations and otherwise uses only very fast symmetric-key primitives. SWiM is secure against semi-honest adversaries. We implemented a prototype of our protocol to demonstrate its practicality. We can perform WPM on a DNA text (4-character alphabet) of length $10^5$ and pattern of length $10^3$ in just over 2 seconds, which is over two orders of magnitude faster than the state-of-the-art scheme of Baron et al. (SCN 2012)

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