A kilobit hidden SNFS discrete logarithm computation

We perform a special number field sieve discrete logarithm computation in a 1024-bit prime field. To our knowledge, this is the first kilobit-sized discrete logarithm computation ever reported for prime fields. This computation took a little over two months of calendar time on an academic cluster using the open-source CADO-NFS software. Our chosen prime $p$ looks random, and $p--1$ has a 160-bit prime factor, in line with recommended parameters for the Digital Signature Algorithm. However, our p has been trapdoored in such a way that the special number field sieve can be used to compute discrete logarithms in $\mathbb{F}\_p^*$ , yet detecting that p has this trapdoor seems out of reach. Twenty-five years ago, there was considerable controversy around the possibility of back-doored parameters for DSA. Our computations show that trapdoored primes are entirely feasible with current computing technology. We also describe special number field sieve discrete log computations carried out for multiple weak primes found in use in the wild. As can be expected from a trapdoor mechanism which we say is hard to detect, our research did not reveal any trapdoored prime in wide use. The only way for a user to defend against a hypothetical trapdoor of this kind is to require verifiably random primes

Differential modulatory effects of GSK-3β and HDM2 on sorafenib-induced AIF nuclear translocation (programmed necrosis) in melanoma

<p>Abstract</p> <p>Background</p> <p>GSK-3β phosphorylates numerous substrates that govern cell survival. It phosphorylates p53, for example, and induces its nuclear export, HDM2-dependent ubiquitination, and proteasomal degradation. GSK-3β can either enhance or inhibit programmed cell death, depending on the nature of the pro-apoptotic stimulus. We previously showed that the multikinase inhibitor sorafenib activated GSK-3β and that this activation attenuated the cytotoxic effects of the drug in various BRAF-mutant melanoma cell lines. In this report, we describe the results of studies exploring the effects of GSK-3β on the cytotoxicity and antitumor activity of sorafenib combined with the HDM2 antagonist MI-319.</p> <p>Results</p> <p>MI-319 alone increased p53 levels and p53-dependent gene expression in melanoma cells but did not induce programmed cell death. Its cytotoxicity, however, was augmented in some melanoma cell lines by the addition of sorafenib. In responsive cell lines, the MI-319/sorafenib combination induced the disappearance of p53 from the nucleus, the down modulation of Bcl-2 and Bcl-x_L, the translocation of p53 to the mitochondria and that of AIF to the nuclei. These events were all GSK-3β-dependent in that they were blocked with a GSK-3β shRNA and facilitated in otherwise unresponsive melanoma cell lines by the introduction of a constitutively active form of the kinase (GSK-3β-S9A). These modulatory effects of GSK-3β on the activities of the sorafenib/MI-319 combination were the exact reverse of its effects on the activities of sorafenib alone, which induced the down modulation of Bcl-2 and Bcl-x_Land the nuclear translocation of AIF only in cells in which GSK-3β activity was either down modulated or constitutively low. In A375 xenografts, the antitumor effects of sorafenib and MI-319 were additive and associated with the down modulation of Bcl-2 and Bcl-x_L, the nuclear translocation of AIF, and increased suppression of tumor angiogenesis.</p> <p>Conclusions</p> <p>Our data demonstrate a complex partnership between GSK-3β and HDM2 in the regulation of p53 function in the nucleus and mitochondria. The data suggest that the ability of sorafenib to activate GSK-3β and alter the intracellular distribution of p53 may be exploitable as an adjunct to agents that prevent the HDM2-dependent degradation of p53 in the treatment of melanoma.</p

Carcass persistence and detectability : reducing the uncertainty surrounding wildlife-vehicle collision surveys

Carcass persistence time and detectability are two main sources of uncertainty on roadkill surveys. In this study, we evaluate the influence of these uncertainties on roadkill surveys and estimates. To estimate carcass persistence time, three observers (including the driver) surveyed 114km by car on a monthly basis for two years, searching for wildlife-vehicle collisions (WVC). Each survey consisted of five consecutive days. To estimate carcass detectability, we randomly selected stretches of 500m to be also surveyed on foot by two other observers (total 292 walked stretches, 146 km walked). We expected that body size of the carcass, road type, presence of scavengers and weather conditions to be the main drivers influencing the carcass persistence times, but their relative importance was unknown. We also expected detectability to be highly dependent on body size. Overall, we recorded low median persistence times (one day) and low detectability (<10%) for all vertebrates. The results indicate that body size and landscape cover (as a surrogate of scavengers' presence) are the major drivers of carcass persistence. Detectability was lower for animals with body mass less than 100g when compared to carcass with higher body mass. We estimated that our recorded mortality rates underestimated actual values of mortality by 2±10 fold. Although persistence times were similar to previous studies, the detectability rates here described are very different from previous studies. The results suggest that detectability is the main source of bias across WVC studies. Therefore, more than persistence times, studies should carefully account for differing detectability when comparing WVC studies

Methamphetamine-Induced Dopamine-Independent Alterations in Striatal Gene Expression in the 6-Hydroxydopamine Hemiparkinsonian Rats

Unilateral injections of 6-hydroxydopamine into the medial forebrain bundle are used extensively as a model of Parkinson's disease. The present experiments sought to identify genes that were affected in the dopamine (DA)–denervated striatum after 6-hydroxydopamine-induced destruction of the nigrostriatal dopaminergic pathway in the rat. We also examined whether a single injection of methamphetamine (METH) (2.5 mg/kg) known to cause changes in gene expression in the normally DA-innervated striatum could still influence striatal gene expression in the absence of DA. Unilateral injections of 6-hydroxydopamine into the medial forebrain bundle resulted in METH-induced rotational behaviors ipsilateral to the lesioned side and total striatal DA depletion on the lesioned side. This injection also caused decrease in striatal serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels. DA depletion was associated with increases in 5-HIAA/5-HT ratios that were potentiated by the METH injection. Microarray analyses revealed changes (± 1.7-fold, p<0.025) in the expression of 67 genes on the lesioned side in comparison to the intact side of the saline-treated hemiparkinsonian animals. These include follistatin, neuromedin U, and tachykinin 2 which were up-regulated. METH administration caused increases in the expression of c-fos, Egr1, and Nor-1 on the intact side. On the DA-depleted side, METH administration also increased the expression of 61 genes including Pdgf-d and Cox-2. There were METH-induced changes in 16 genes that were common in the DA-innervated and DA-depleted sides. These include c-fos and Nor-1 which show greater changes on the normal DA side. Thus, the present study documents, for the first time, that METH mediated DA-independent changes in the levels of transcripts of several genes in the DA-denervated striatum. Our results also implicate 5-HT as a potential player in these METH-induced alterations in gene expression because the METH injection also caused significant increases in 5-HIAA/5-HT ratios on the DA-depleted side

Basal monothalamous and pseudochambered benthic foraminifera associated with planktonic foraminiferal shells and mineral grains from the Porcupine Abyssal Plain, NE Atlantic

We present a survey of ‘live’ (stained) and dead monothalamous (single-chambered, mainly spherical) and pseudochambered (chain-like) foraminifera associated with planktonic foraminiferal shells and mineral grains, based on two samples from one abyssal plain site (F2, 4,880 m water depth) and one abyssal hill site (H4, 4,330 m water depth) on the Porcupine Abyssal Plain (PAP), northeast Atlantic. Our study is the first to focus on this poorly known component of abyssal foraminiferal faunas and highlight their abundances and diversity at the PAP. In both samples these monothalamids and pseudochambered forms represented 27–35 % and 18–23 %, respectively, of the entire ‘live’ and dead foraminiferal assemblage (&gt;150 ?m, 0–1 cm sediment layer). Among 1,078 stained and dead specimens we recognise a total of 18 distinct morphotypes on the basis of test characteristics. Another 144 specimens could not be assigned to any morphotype and are regarded as indeterminate. Most of the monothalamids are small (&lt;150 ?m), although some incorporate planktonic foraminiferal shells to create larger structures. In absolute terms, stained and dead individuals of these morphotypes were more abundant at the abyssal hill site, although data from additional samples are needed to confirm if this is representative of differences between abyssal hills and the surrounding abyssal plain at the PAP. Agglutinated spheres and domes similar to some of our abyssal forms have been reported from shelf and slope settings, but they are generally much larger. Small agglutinated spheres are very common in the abyssal Pacific, at depths close to or below the carbonate compensation depth (CCD). However, they are composed largely of siliceous particles, including mineral grains, radiolarians and diatom fragments. In contrast, carbonate oozes at the PAP, situated above the CCD, are rich in coccoliths and planktonic foraminiferal shells, which are used in the construction of agglutinated spheres and domes. Our results underline the important contribution made by largely underestimated foraminiferal taxa to abyssal communities