Policy instruments in the Common Agricultural Policy

Policy changes in the Common Agricultural Policy (CAP) can be explained in terms of the exhaustion and long-term contradictions of policy instruments. Changes in policy instruments have reoriented the policy without any change in formal Treaty goals. The social and economic efficacy of instruments in terms of evidence-based policy analysis was a key factor in whether they were delegitimized. The original policy instruments were generally dysfunctional, but reframing the policy in terms of a multifunctionality paradigm permitted the development of more efficacious instruments. A dynamic interaction takes place between the instruments and policy informed by the predominant discourses

The effect of soy isoflavones on steroid metabolism

Objective: This study is a post-hoc analysis of steroid hormones before and after administration of pharmacological doses of soy isoflavones in a large cohort of men and women from two independent studies. Isoflavones are reported to inhibit mineralo- and glucocorticoid hormone production as well as reproductive steroids in vivo and in vitro. We focused on cytochrome P450 17α-hydroxylase (CYP17A1) which catalyses the production of dehydroepiandrosterone (DHEA), in the androgen biosynthesis pathway to elucidate effects on sex steroids in vitro. Design and Setting: Effects of soy isoflavones on steroid levels in two studies comprising 400 patients were examined: 200 men (study 1; 3 months duration) and 200 postmenopausal women (study 2; 6 months duration), randomized to consume 15 g soy protein with 66 mg isoflavones (SPI) or 15 g soy protein alone without isoflavones (SP) daily. Effects of genistein and daidzein on steroid metabolism were determined in vitro, in HEK293 cells expressing CYP17A1 and in the human adrenocortical carcinoma H295R cell model. Results: SPI decreased serum dehydroepiandrosterone sulfate (DHEAS) levels in both men and women (P < 0.01), with decreased androstenedione (A4) (P < 0.01) in women not observed in men (P < 0.86). Cortisol, cortisone, 11-deoxycortisol, aldosterone, testosterone (T), or estradiol (E2) levels were unchanged. The dual hydroxylase and lyase activity of CYP17A1, which catalyses the biosynthesis of androgen precursors, and 3β-hydroxysteroid dehydrogenase (3βHSD2) were investigated in vitro. In transiently transfected HEK293 cells, only the lyase activity was inhibited by both genistein, 20% (P < 0.001) and daidzein, 58% (P < 0.0001). In forskolin-stimulated H295R cells DHEA production was decreased by daidzein (P < 0.05) and genistein, confirming inhibition of the lyase activity by the isoflavones. Conclusion: In Vivo clinical data suggested inhibition of CYP17A1 17,20 lyase within the adrenal in men and within the ovary and adrenal in females. This was confirmed in vitro with inhibition of the lyase activity by both genistein and daidzein. In addition, 3βHSD2 was inhibited perhaps accounting for decreased A4 levels observed in females. The decreased DHEAS and A4 levels together with the inhibition of the 17,20 lyase activity of CYP17A1, may impact production of androgens in clinical conditions associated with androgen excess

The functional analysis of nonsense suppressors derived from in vitro engineered \u3ci\u3eSaccharomyces cerevisiae\u3c/i\u3e tRNA\u3csup\u3eTrp\u3c/sup\u3e genes

Nonsense suppressors derived from Saccharomyces cerevisiae tRNATrp genes have not been identified by classical genetic screens, although one can construct efficient amber (am) suppressors from them by making the appropriate anticodon mutation in vitro. Herein, a series of in vitro constructed putative suppressor genes was produced to test if pre-tRNATrp processing difficulties could help to explain the lack of classical tRNATrp-based suppressors. It is clear that inefficient processing of in-trons from precursor tRNATrp, or inaccurate overall processing, may explain why some of these constructs fail to promote nonsense suppression in vivo. However, deficient processing must be only one of the reasons why classical tRNATrp-based suppressors have not been characterized, as suppres-sion may still be extremely weak or absent in instances where the in vitro construct can lead to an accumulation of mature tRNATrp. Furthermore, suppression is also very weak in strains transformed with an intronless derivative of a putative tRNATrp ochre (oc) suppressor gene, wherein intron removal cannot pose a problem

The functional analysis of nonsense suppressors derived from in vitro engineered \u3ci\u3eSaccharomyces cerevisiae\u3c/i\u3e tRNA\u3csup\u3eTrp\u3c/sup\u3e genes

Nonsense suppressors derived from Saccharomyces cerevisiae tRNATrp genes have not been identified by classical genetic screens, although one can construct efficient amber (am) suppressors from them by making the appropriate anticodon mutation in vitro. Herein, a series of in vitro constructed putative suppressor genes was produced to test if pre-tRNATrp processing difficulties could help to explain the lack of classical tRNATrp-based suppressors. It is clear that inefficient processing of in-trons from precursor tRNATrp, or inaccurate overall processing, may explain why some of these constructs fail to promote nonsense suppression in vivo. However, deficient processing must be only one of the reasons why classical tRNATrp-based suppressors have not been characterized, as suppres-sion may still be extremely weak or absent in instances where the in vitro construct can lead to an accumulation of mature tRNATrp. Furthermore, suppression is also very weak in strains transformed with an intronless derivative of a putative tRNATrp ochre (oc) suppressor gene, wherein intron removal cannot pose a problem

Lessons from building an automated pre-departure sequencer for airports

Commercial airports are under increasing pressure to comply with the Eurocontrol collaborative decision making (CDM) initiative, to ensure that information is passed between stakeholders, integrate automated decision support or make predictions. These systems can also aid effective operations beyond the airport by communicating scheduling decisions to other relevant parties, such as Eurocontrol, for passing on to downstream airports and enabling overall airspace improvements. One of the major CDM components is aimed at producing the target take-off times and target startup-approval times, i.e. scheduling when the aircraft should push back from the gates and start their engines and when they will take off. For medium-sized airports, a common choice for this is a “pre-departure sequencer” (PDS). In this paper, we describe the design and requirements challenges which arose during our development of a PDS system for medium sized international airports. Firstly, the scheduling problem is highly dynamic and event driven. Secondly, it is important to end-users that the system be predictable and, as far as possible, transparent in its operation, with decisions that can be explained. Thirdly, users can override decisions, and this information has to be taken into account. Finally, it is important that the system is as fair as possible for all users of the airport, and the interpretation of this is considered here. Together, these factors have influenced the design of the PDS system which has been built to work within an existing large system which is being used at many airport

Thoughts on Quorum Sensing and Fungal Dimorphism

Farnesol has been best studied for its role in regulating fungal dimorphism. However, farnesol is also a lipid and in this review we analyze data relevant to farnesol’s function and synthesis from the perspective of farnesol and bacterial endotoxins acting as membrane active compounds. This analysis implicates the possible roles of: (1) endotoxins in the regulation of farnesol production by C. albicans; (2) farnesol in the interactions between C. albicans and the host during disseminated infections; and (3) ubiquinones in the mechanisms for unusually high resistance to farnesol by some C. albicans cell types. Finally we discuss the implications that the use of farnesol as both a signaling molecule and to antagonize competing microbials species has for the regulation of HMG-CoA reductase, the enzyme that is the usual rate limiting step in sterol/lipid synthesis

Thoughts on Quorum Sensing and Fungal Dimorphism

Farnesol has been best studied for its role in regulating fungal dimorphism. However, farnesol is also a lipid and in this review we analyze data relevant to farnesol’s function and synthesis from the perspective of farnesol and bacterial endotoxins acting as membrane active compounds. This analysis implicates the possible roles of: (1) endotoxins in the regulation of farnesol production by C. albicans; (2) farnesol in the interactions between C. albicans and the host during disseminated infections; and (3) ubiquinones in the mechanisms for unusually high resistance to farnesol by some C. albicans cell types. Finally we discuss the implications that the use of farnesol as both a signaling molecule and to antagonize competing microbials species has for the regulation of HMG-CoA reductase, the enzyme that is the usual rate limiting step in sterol/lipid synthesis

Halving Balls in Deterministic Linear Time

Let \D be a set of $n$ pairwise disjoint unit balls in $\R^d$ and $P$ the set of their center points. A hyperplane \Hy is an \emph{$m$-separator} for \D if each closed halfspace bounded by \Hy contains at least $m$ points from $P$. This generalizes the notion of halving hyperplanes, which correspond to $n/2$-separators. The analogous notion for point sets has been well studied. Separators have various applications, for instance, in divide-and-conquer schemes. In such a scheme any ball that is intersected by the separating hyperplane may still interact with both sides of the partition. Therefore it is desirable that the separating hyperplane intersects a small number of balls only. We present three deterministic algorithms to bisect or approximately bisect a given set of disjoint unit balls by a hyperplane: Firstly, we present a simple linear-time algorithm to construct an $\alpha n$-separator for balls in $\R^d$, for any $0<\alpha<1/2$, that intersects at most $cn^{(d-1)/d}$ balls, for some constant $c$ that depends on $d$ and $\alpha$. The number of intersected balls is best possible up to the constant $c$. Secondly, we present a near-linear time algorithm to construct an $(n/2-o(n))$-separator in $\R^d$ that intersects $o(n)$ balls. Finally, we give a linear-time algorithm to construct a halving line in $\R^2$ that intersects $O(n^{(5/6)+\epsilon})$ disks. Our results improve the runtime of a disk sliding algorithm by Bereg, Dumitrescu and Pach. In addition, our results improve and derandomize an algorithm to construct a space decomposition used by L{\"o}ffler and Mulzer to construct an onion (convex layer) decomposition for imprecise points (any point resides at an unknown location within a given disk)

Higher Order Analogues of Tracy-Widom Distributions via the Lax Method

We study the distribution of the largest eigenvalue in formal Hermitian one-matrix models at multicriticality, where the spectral density acquires an extra number of k-1 zeros at the edge. The distributions are directly expressed through the norms of orthogonal polynomials on a semi-infinite interval, as an alternative to using Fredholm determinants. They satisfy non-linear recurrence relations which we show form a Lax pair, making contact to the string literature in the early 1990's. The technique of pseudo-differential operators allows us to give compact expressions for the logarithm of the gap probability in terms of the Painleve XXXIV hierarchy. These are the higher order analogues of the Tracy-Widom distribution which has k=1. Using known Backlund transformations we show how to simplify earlier equivalent results that are derived from Fredholm determinant theory, valid for even k in terms of the Painleve II hierarchy.Comment: 24 pages. Improved discussion of Backlund transformations, in addition to other minor improvements in text. Typos corrected. Matches published versio