β‐Ionone: Its Occurrence and Biological Function and Metabolic Engineering

β‐Ionone is a natural plant volatile compound, and it is the 9,10 and 9’,10’ cleavage prod-uct of β‐carotene by the carotenoid cleavage dioxygenase. β‐Ionone is widely distributed in flowers, fruits, and vegetables. β‐Ionone and other apocarotenoids comprise flavors, aromas, pigments, growth regulators, and defense compounds; serve as ecological cues; have roles as insect attractants or repellants, and have antibacterial and fungicidal properties. In recent years, β‐ionone has also received increased attention from the biomedical community for its potential as an anticancer treatment and for other human health benefits. However, β‐ionone is typically produced at relatively low levels in plants. Thus, expressing plant biosynthetic pathway genes in microbial hosts and engineering the metabolic pathway/host to increase metabolite production is an appealing alternative. In the present review, we discuss β‐ionone occurrence, the biological activities of β‐ionone, empha-sizing insect attractant/repellant activities, and the current strategies and achievements used to re-construct enzyme pathways in microorganisms in an effort to to attain higher amounts of the de-sired β‐ionone

Simple extractors via constructions of cryptographic pseudo-random generators

Trevisan has shown that constructions of pseudo-random generators from hard functions (the Nisan-Wigderson approach) also produce extractors. We show that constructions of pseudo-random generators from one-way permutations (the Blum-Micali-Yao approach) can be used for building extractors as well. Using this new technique we build extractors that do not use designs and polynomial-based error-correcting codes and that are very simple and efficient. For example, one extractor produces each output bit separately in $O(\log^2 n)$ time. These extractors work for weak sources with min entropy $\lambda n$, for arbitrary constant $\lambda > 0$, have seed length $O(\log^2 n)$, and their output length is $\approx n^{\lambda/3}$.Comment: 21 pages, an extended abstract will appear in Proc. ICALP 2005; small corrections, some comments and references adde

Constructive Dimension and Turing Degrees

This paper examines the constructive Hausdorff and packing dimensions of Turing degrees. The main result is that every infinite sequence S with constructive Hausdorff dimension dim_H(S) and constructive packing dimension dim_P(S) is Turing equivalent to a sequence R with dim_H(R) <= (dim_H(S) / dim_P(S)) - epsilon, for arbitrary epsilon > 0. Furthermore, if dim_P(S) > 0, then dim_P(R) >= 1 - epsilon. The reduction thus serves as a *randomness extractor* that increases the algorithmic randomness of S, as measured by constructive dimension. A number of applications of this result shed new light on the constructive dimensions of Turing degrees. A lower bound of dim_H(S) / dim_P(S) is shown to hold for the Turing degree of any sequence S. A new proof is given of a previously-known zero-one law for the constructive packing dimension of Turing degrees. It is also shown that, for any regular sequence S (that is, dim_H(S) = dim_P(S)) such that dim_H(S) > 0, the Turing degree of S has constructive Hausdorff and packing dimension equal to 1. Finally, it is shown that no single Turing reduction can be a universal constructive Hausdorff dimension extractor, and that bounded Turing reductions cannot extract constructive Hausdorff dimension. We also exhibit sequences on which weak truth-table and bounded Turing reductions differ in their ability to extract dimension.Comment: The version of this paper appearing in Theory of Computing Systems, 45(4):740-755, 2009, had an error in the proof of Theorem 2.4, due to insufficient care with the choice of delta. This version modifies that proof to fix the error

Field cooling memory effect in Bi2212 and Bi2223 single crystals

A memory effect in the Josephson vortex system created by magnetic field in the highly anisotropic superconductors Bi2212 and Bi2223 is demonstrated using microwave power absorption. This surprising effect appears despite a very low viscosity of Josephson vortices compared to Abrikosov vortices. The superconductor is field cooled in DC magnetic field H_{m} oriented parallel to the CuO planes through the critical temperature T_{c} down to 4K, with subsequent reduction of the field to zero and again above H_{m}. Large microwave power absorption signal is observed at a magnetic field just above the cooling field clearly indicating a memory effect. The dependence of the signal on deviation of magnetic field from H_{m} is the same for a wide range of H_{m} from 0.15T to 1.7T

On Obtaining Pseudorandomness from Error-Correcting Codes

A number of recent results have constructed randomness extractors and pseudorandom generators (PRGs) directly from certain error-correcting codes. The underlying construction in these results amounts to picking a random index into the codeword and outputting m consecutive symbols (the codeword is obtained from the weak random source in the case of extractors, and from a hard function in the case of PRGs). We study this construction applied to general cyclic error-correcting codes, with the goal of understanding what pseudorandom objects it can produce. We show that every cyclic code with sufficient distance yields extractors that fool all linear tests. Further, we show that every polynomial code with sufficient distance yields extractors that fool all low-degree prediction tests. These are the first results that apply to univariate (rather than multivariate) polynomial codes, hinting that Reed-Solomon codes may yield good randomness extractors. Our proof technique gives rise to a systematic way of producing unconditional PRGs against restricted classes of tests. In particular, we obtain PRGs fooling all linear tests (which amounts to a construction of ε-biased spaces), and we obtain PRGs fooling all low-degree prediction tests

Non-Malleable Codes Against Bounded Polynomial Time Tampering

We construct efficient non-malleable codes (NMC) that are (computationally) secure against tampering by functions computable in any fixed polynomial time. Our construction is in the plain (no-CRS) model and requires the assumptions that (1) $\mathbf{E}$ is hard for $\mathbf{NP}$ circuits of some exponential $2^{\beta n}$ ($\beta>0$) size (widely used in the derandomization literature), (2) sub-exponential trapdoor permutations exist, and (3) $\mathbf{P}$ certificates with sub-exponential soundness exist. While it is impossible to construct NMC secure against arbitrary polynomial-time tampering (Dziembowski, Pietrzak, Wichs, ICS \u2710), the existence of NMC secure against $O(n^c)$-time tampering functions (for any fixed $c$), was shown (Cheraghchi and Guruswami, ITCS \u2714) via a probabilistic construction. An explicit construction was given (Faust, Mukherjee, Venturi, Wichs, Eurocrypt \u2714) assuming an untamperable CRS with length longer than the runtime of the tampering function. In this work, we show that under computational assumptions, we can bypass these limitations. Specifically, under the assumptions listed above, we obtain non-malleable codes in the plain model against $O(n^c)$-time tampering functions (for any fixed $c$), with codeword length independent of the tampering time bound. Our new construction of NMC draws a connection with non-interactive non-malleable commitments. In fact, we show that in the NMC setting, it suffices to have a much weaker notion called quasi non-malleable commitments---these are non-interactive, non-malleable commitments in the plain model, in which the adversary runs in $O(n^c)$-time, whereas the honest parties may run in longer (polynomial) time. We then construct a 4-tag quasi non-malleable commitment from any sub-exponential OWF and the assumption that $\mathbf{E}$ is hard for some exponential size $\mathbf{NP}$-circuits, and use tag amplification techniques to support an exponential number of tags

Distinct phosphatases antagonize the p53 response in different phases of the cell cycle

The basic machinery that detects DNA damage is the same throughout the cell cycle. Here, we show, in contrast, that reversal of DNA damage responses (DDRs) and recovery are fundamentally different in G1 and G2 phases of the cell cycle. We find that distinct phosphatases are required to counteract the checkpoint response in G1 vs. G2. Whereas WT p53-induced phosphatase 1 (Wip1) promotes recovery in G2-arrested cells by antagonizing p53, it is dispensable for recovery from a G1 arrest. Instead, we identify phosphoprotein phosphatase 4 catalytic subunit (PP4) to be specifically required for cell cycle restart after DNA damage in G1. PP4 dephosphorylates Krüppel-associated box domain-associated protein 1-S473 to repress p53-dependent transcriptional activation of p21 when the DDR is silenced. Taken together, our results show that PP4 and Wip1 are differentially required to counteract the p53-dependent cell cycle arrest in G1 and G2, by antagonizing early or late p53-mediated responses, respectively

Efficient and Provable White-Box Primitives

International audienceIn recent years there have been several attempts to build white-box block ciphers whose implementations aim to be incompress-ible. This includes the weak white-box ASASA construction by Bouil-laguet, Biryukov and Khovratovich from Asiacrypt 2014, and the recent space-hard construction by Bogdanov and Isobe from CCS 2015. In this article we propose the first constructions aiming at the same goal while offering provable security guarantees. Moreover we propose concrete instantiations of our constructions, which prove to be quite efficient and competitive with prior work. Thus provable security comes with a surprisingly low overhead

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD