ADESS: A Proof-of-Work Protocol to Deter Double-Spend Attacks

A principal vulnerability of a proof-of-work ("PoW") blockchain is that an attacker can re-write the history of transactions by forking a previously published block and build a new chain segment containing a different sequence of transactions. If the attacker's chain has the most cumulative mining puzzle difficulty, nodes will recognize it as canonical. We propose a modification to PoW protocols, called ADESS, that contains two novel features. The first modification enables a node to identify the attacker chain by comparing the temporal sequence of blocks on competing chains. The second modification penalizes the attacker by requiring it to apply exponentially increasing hashrate in order to make its chain canonical. We demonstrate two things; (i) the expected cost of carrying out a double-spend attack is weakly higher under ADESS compared to the current PoW protocols and (ii) for any value of transaction, there is a penalty setting in ADESS that renders the expected profit of a double-spend attack negative.Comment: 33 pages. Accepted at Future of Information and Communications Conference 202

Linking the Pinware, Baraboo, and Picuris Orogens: Recognition of a Trans-Laurentian ca. 1520–1340 Ma Orogenic Belt

It is proposed that the Pinware orogen of eastern Canada, the Baraboo orogen of the midcontinent, and the Picuris orogen of the southwestern United States delineate a previously unrecognized, ~5000-km-long, ca. 1520–1340 Ma trans-Laurentian orogenic belt. All three orogenic provinces are characterized by Mesoproterozoic sedimentation, magmatism, metamorphism, and deformation—the hallmarks of a tectonically active plate margin. Tectonism was diachronous, with the earliest stages beginning ca. 1520 Ma in eastern Canada and ca. 1500 Ma in the southwest United States. Magmatic zircon age distributions are dominated by Mesoproterozoic, unimodal to multimodal age peaks between ca. 1500 and 1340 Ma. The onset of magmatism in the Pinware and Baraboo orogens was ca. 1520 Ma, and onset for the Picuris orogen was ca. 1485 Ma. Detrital zircon age distributions within each orogenic province yield maximum depositional ages between ca. 1570 and 1450 Ma. Minimum depositional ages generally fall between ca. 1500 and 1435 Ma, as constrained by crosscutting intrusions, metatuff layers, or the age of subsequent metamorphism. Metamorphic mineral growth ages from zircon, garnet, and monazite yield peak ages between ca. 1500 and 1350 Ma and tend to be older in the Pinware and Baraboo orogens than in the Picuris orogen. The 40Ar/39Ar cooling ages for hornblende, muscovite, and biotite yield significant peak ages between ca. 1500 and 1350 Ma in the Baraboo and Picuris orogens. We propose that the Pinware-Baraboo-Picuris orogen formed in a complex, diachronous, convergent margin setting along the southern edge of Laurentia from ca. 1520 to 1340 Ma

A-Kinase Anchoring in Dendritic Cells Is Required for Antigen Presentation

BACKGROUND: Dendritic cells (DC) are the most potent antigen presenting cells (APC) of the immune system. Prostaglandin E(2), cyclic AMP, and protein kinase A (PKA) have all been shown to regulate DC maturation and activity. In other cells, the ability of these molecules to convey their signals has been shown to be dependent on A-kinase anchoring proteins (AKAPs). Here we present evidence for the existence and functional importance of AKAPs in human DC. METHODOLOGY/PRINCIPAL FINDINGS: Using immunofluorescence and/or western analyses we identify AKAP79, AKAP149, AKAP95, AKAP LBC and Ezrin. We also demonstrate by western analysis that expression of AKAP79, AKAP149 and RII are upregulated with DC differentiation and maturation. We establish the functional importance of PKA anchoring in multiple aspects of DC biology using the anchoring inhibitor peptides Ht31 and AKAP-IS. Incubation of protein or peptide antigen loaded DC with Ht31 or AKAP-IS results in a 30-50% decrease in antigen presentation as measured by IFN-gamma production from antigen specific CD4(+) T cells. Incubation of LPS treated DC with Ht31 results in 80% inhibition of TNF-alpha and IL-10 production. Ht31 slightly decreases the expression of CD18 and CD11a and CD11b, slightly increases the basal expression of CD83, dramatically decreases the LPS stimulated expression of CD40, CD80 and CD83, and significantly increases the expression of the chemokine receptor CCR7. CONCLUSIONS: These experiments represent the first evidence for the functional importance of PKA anchoring in multiple aspects of DC biology

Early Onset Prion Disease from Octarepeat Expansion Correlates with Copper Binding Properties

Insertional mutations leading to expansion of the octarepeat domain of the prion protein (PrP) are directly linked to prion disease. While normal PrP has four PHGGGWGQ octapeptide segments in its flexible N-terminal domain, expanded forms may have up to nine additional octapeptide inserts. The type of prion disease segregates with the degree of expansion. With up to four extra octarepeats, the average onset age is above 60 years, whereas five to nine extra octarepeats results in an average onset age between 30 and 40 years, a difference of almost three decades. In wild-type PrP, the octarepeat domain takes up copper (Cu2+) and is considered essential for in vivo function. Work from our lab demonstrates that the copper coordination mode depends on the precise ratio of Cu2+ to protein. At low Cu2+ levels, coordination involves histidine side chains from adjacent octarepeats, whereas at high levels each repeat takes up a single copper ion through interactions with the histidine side chain and neighboring backbone amides. Here we use both octarepeat constructs and recombinant PrP to examine how copper coordination modes are influenced by octarepeat expansion. We find that there is little change in affinity or coordination mode populations for octarepeat domains with up to seven segments (three inserts). However, domains with eight or nine total repeats (four or five inserts) become energetically arrested in the multi-histidine coordination mode, as dictated by higher copper uptake capacity and also by increased binding affinity. We next pooled all published cases of human prion disease resulting from octarepeat expansion and find remarkable agreement between the sudden length-dependent change in copper coordination and onset age. Together, these findings suggest that either loss of PrP copper-dependent function or loss of copper-mediated protection against PrP polymerization makes a significant contribution to early onset prion disease

An Estimate of Avian Mortality at Communication Towers in the United States and Canada

Avian mortality at communication towers in the continental United States and Canada is an issue of pressing conservation concern. Previous estimates of this mortality have been based on limited data and have not included Canada. We compiled a database of communication towers in the continental United States and Canada and estimated avian mortality by tower with a regression relating avian mortality to tower height. This equation was derived from 38 tower studies for which mortality data were available and corrected for sampling effort, search efficiency, and scavenging where appropriate. Although most studies document mortality at guyed towers with steady-burning lights, we accounted for lower mortality at towers without guy wires or steady-burning lights by adjusting estimates based on published studies. The resulting estimate of mortality at towers is 6.8 million birds per year in the United States and Canada. Bootstrapped subsampling indicated that the regression was robust to the choice of studies included and a comparison of multiple regression models showed that incorporating sampling, scavenging, and search efficiency adjustments improved model fit. Estimating total avian mortality is only a first step in developing an assessment of the biological significance of mortality at communication towers for individual species or groups of species. Nevertheless, our estimate can be used to evaluate this source of mortality, develop subsequent per-species mortality estimates, and motivate policy action