Game-Theoretic Analysis of (Non-)Refundable Fees in the Lightning Network

In PCNs, nodes that forward payments between a source and a receiver are paid a small fee if the payment is successful. The fee is a compensation for temporarily committing funds to the payment. However, payments may fail due to insufficient funds or attacks, often after considerable delays of up to several days, leaving a node without compensation. Furthermore, attackers can intentionally cause failed payments, e.g., to infer private information (like channel balances), without any cost in fees. In this paper, we first use extensive form games to formally characterize the conditions that lead to rational intermediaries refusing (or agreeing) to forward payments. A decision made by an intermediary to forward or not depends on the probability of failure, which they approximate based on past experience. We then propose and analyze an alternative fee model that allows the sender to determine and pay a fraction of the fee to intermediaries in a non refundable manner. A rational sender chooses the fraction such that the intermediaries' utility for forwarding the payment exceeds their utility for not forwarding. Our simulation study, based on real world Lightning snapshots, confirms that our novel mechanism can increase the probability of successful payments by 12 percent and decrease routing fees for senders by about 6 percent if all nodes behave rationally. Furthermore, previously cost free probing attacks now require that the attacker pays 1500 satoshis for every 1 million satoshis inferred. Finally, we propose a modification to the Hash Time Locked Contract to enable secure payments of the non refundable fees

Autorijden met ADHD

Volwassenen met attention deficit hyperactivity disorder (ADHD) hebben uiteenlopende cognitieve beperkingen, die een aanzienlijke invloed kunnen hebben op verschillende aspecten van het dagelijks leven. Een van deze aspecten is het besturen van een auto. Autorijden is een belangrijke activiteit in het dagelijks leven en vereist een adequate wisselwerking tussen verschillende vaardigheden en het op elkaar afgestemd zijn van verschillende functies. Dit artikel geeft een overzicht van studies die zich hebben gericht op de aan ADHD gerelateerde problemen met autorijden. Hierbij staan drie vragen centraal: 1) laten personen met ADHD in sterkere mate onveilig rijgedrag zien dan personen zonder ADHD, 2) welke cognitieve (dis)functies van personen met ADHD zijn gerelateerd aan onveilig autorijden en 3) kan farmaceutische behandeling het rijgedrag van adolescenten en volwassenen met ADHD significant verbeteren? Het beschikbare onderzoek levert overtuigend bewijs dat personen met ADHD gekenmerkt worden door meer negatief rijgedrag dan personen zonder ADHD. Het blijkt echter dat niet alle personen met ADHD op dezelfde manier zijn aangedaan. Hoewel verschillende cognitieve functies gerelateerd zijn aan rijvaardigheid, lijken deze functies noch bij te dragen aan het detecteren van high risk automobilisten met ADHD, noch aan het voorspellen van rijgedrag bij personen met ADHD. Farmaceutische behandeling van ADHD, in het bijzonder stimulerende medicatie, lijkt bevorderlijk voor de rijvaardigheid van personen met ADHD

Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection

Antibodies against the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can drive adaptive evolution in immunocompromised patients with chronic infection. Here we longitudinally analyze SARS-CoV-2 sequences in a B cell-depleted, lymphoma patient with chronic, ultimately fatal infection, and identify three mutations in the spike protein that dampen convalescent plasma-mediated neutralization of SARS-CoV-2. Additionally, four mutations emerge in non-spike regions encoding three CD8 T cell epitopes, including one nucleoprotein epitope affected by two mutations. Recognition of each mutant peptide by CD8 T cells from convalescent donors is reduced compared to its ancestral peptide, with additive effects resulting from double mutations. Querying public SARS-CoV-2 sequences shows that these mutations have independently emerged as homoplasies in circulating lineages. Our data thus suggest that potential impacts of CD8 T cells on SARS-CoV-2 mutations, at least in those with humoral immunodeficiency, warrant further investigation to inform on vaccine design

Whole exome resequencing reveals recessive mutations in TRAP1 in individuals with CAKUT and VACTERL association

Congenital abnormalities of the kidney and urinary tract (CAKUT) account for approximately half of children with chronic kidney disease and they are the most frequent cause of end-stage renal disease in children in the US. However, its genetic etiology remains mostly elusive. VACTERL association is a rare disorder that involves congenital abnormalities in multiple organs including the kidney and urinary tract in up to 60% of the cases. By homozygosity mapping and whole exome resequencing combined with high-throughput mutation analysis by array-based multiplex PCR and next-generation sequencing, we identified recessive mutations in the gene TNF receptor-associated protein 1 (TRAP1) in two families with isolated CAKUT and three families with VACTERL association. TRAP1 is a heat shock protein 90-related mitochondrial chaperone possibly involved in antiapoptotic and endoplasmic reticulum-stress signaling. Trap1 is expressed in renal epithelia of developing mouse kidney E13.5 and in the kidney of adult rats, most prominently in proximal tubules and in thick medullary ascending limbs of Henle’s loop. Thus, we identified mutations in TRAP1 as highly likely causing CAKUT or CAKUT in VACTERL association

Inherited variants in CHD3 show variable expressivity in Snijders Blok-Campeau syndrome

Purpose: Common diagnostic next-generation sequencing strategies are not optimized to identify inherited variants in genes associated with dominant neurodevelopmental disorders as causal when the transmitting parent is clinically unaffected, leaving a significant number of cases with neurodevelopmental disorders undiagnosed. Methods: We characterized 21 families with inherited heterozygous missense or protein-truncating variants in CHD3, a gene in which de novo variants cause Snijders Blok-Campeau syndrome. Results: Computational facial and Human Phenotype Ontology–based comparisons showed that the phenotype of probands with inherited CHD3 variants overlaps with the phenotype previously associated with de novo CHD3 variants, whereas heterozygote parents are mildly or not affected, suggesting variable expressivity. In addition, similarly reduced expression levels of CHD3 protein in cells of an affected proband and of healthy family members with a CHD3 protein-truncating variant suggested that compensation of expression from the wild-type allele is unlikely to be an underlying mechanism. Notably, most inherited CHD3 variants were maternally transmitted. Conclusion: Our results point to a significant role of inherited variation in Snijders Blok-Campeau syndrome, a finding that is critical for correct variant interpretation and genetic counseling and warrants further investigation toward understanding the broader contributions of such variation to the landscape of human disease

Evidence for increases in vegetation species richness across UK Environmental Change Network sites linked to changes in air pollution and weather patterns

We analysed trends in vegetation monitored at regular intervals over the past two decades (1993–2012)at the twelve terrestrial Environmental Change Network (ECN) sites. We sought to determine the extent to which flora had changed and link any such changes to potential environmental drivers. We observed significant increases in species richness, both at a whole network level, and when data were analysed within Broad Habitat groupings representing the open uplands, open lowlands and woodlands. We also found comparable increases in an indicator of vegetation response to soil pH, Ellenberg R. Species characteristic of less acid soils tended to show more consistent increases in frequency across sites relative to species with a known tolerance for strongly acidic soils. These changes are, therefore, broadly consistent with a response to increases in soil solution pH observed for the majority of ECN sites that, in turn, are likely to be driven by large reductions in acid deposition in recent decades. Increases in species richness in certain habitat groupings could also be linked to increased soil moisture availability in drier lowland sites that are likely to have been influenced by a trend towards wetter summers in recent years, and possibly also to a reduction in soil nitrogen availability in some upland locations. Changes in site management are also likely to have influenced trends at certain sites, particularly with respect to agricultural practices. Our results are therefore indicative of wide-scale responses to major regional-scale changes in air pollution and recent weather patterns, modified by local management effects. The relative consistency of management of ECN sites over time is atypical of much of the wider countryside and it is therefore not appropriate to scale up these observations to infer national scale trends. Nevertheless the results provide an important insight into processes that may be operating nationally. It will now be necessary to test for the ubiquity of these changes using appropriate broader spatial scale survey data

Epigenomic and transcriptomic approaches in the post-genomic era: path to novel targets for diagnosis and therapy of the ischemic heart?

Despite advances in myocardial reperfusion therapies, acute myocardial ischemia/reperfusion injury and consequent ischemic heart failure represent the number one cause of morbidity and mortality in industrialized societies. Although different therapeutic interventions have been shown beneficial in preclinical settings, an effective cardioprotective or regenerative therapy has yet to be successfully introduced in the clinical arena. Given the complex pathophysiology of the ischemic heart, large scale, unbiased, global approaches capable of identifying multiple branches of the signaling networks activated in the ischemic/reperfused heart might be more successful in the search for novel diagnostic or therapeutic targets. High-throughput techniques allow high-resolution, genome-wide investigation of genetic variants, epigenetic modifications and associated gene expression profiles. Platforms such as proteomics and metabolomics (not described here in detail) also offer simultaneous readouts of hundreds of proteins and metabolites. Isolated omics analyses usually provide Big Data requiring large data storage, advanced computational resources and complex bioinformatics tools. The possibility of integrating different omics approaches gives new hope to better understand the molecular circuitry activated by myocardial ischemia, putting it in the context of the human "diseasome".Since modifications of cardiac gene expression have been consistently linked to pathophysiology of the ischemic heart, the integration of epigenomic and transcriptomic data seems a promising approach to identify crucial disease networks. Thus, the scope of this Position Paper will be to highlight potentials and limitations of these approaches, and to provide recommendations to optimize the search for novel diagnostic or therapeutic targets for acute ischemia/reperfusion injury and ischemic heart failure in the post-genomic era

Trends and variability in weather and atmospheric deposition at UK Environmental Change Network sites (1993–2012)

We characterised temporal trends and variability in key indicators of climate and atmospheric deposition chemistry at the twelve terrestrial UK Environmental Change Network (ECN) sites over the first two decades of ECN monitoring (1993–2012) using various statistical approaches. Mean air temperatures for the monitoring period were approximately 0.7 °C higher than those modelled for 1961–1990, but there was little evidence for significant change in air temperature over either the full monthly records or within individual seasons. Some upland ECN sites, however, warmed significantly over the first decade before cooling in the second. Summers at most sites became progressively wetter, and extremes in daily rainfall increased in magnitude. Average wind speeds in winter and spring declined at the majority of sites. Directional trends in summer precipitation could be linked to an atypically prolonged negative deviation in the summer North Atlantic Oscillation (NAO) Index. Several aspects of air quality improved markedly. Concentrations and fluxes of sulphate in precipitation declined significantly and substantially across the network, particularly during the earlier years and at the most polluted sites in the south and east. Precipitation concentrations of nitrate and ammonium, and atmospheric concentrations of nitrogen dioxide also decreased at most sites. There was less evidence for reductions in the loads of wet deposited nitrogen species, while trends in atmospheric ammonia concentration varied in direction and strength between sites. Reductions in acid deposition are likely to account for widespread gradual increases in the pH of soil water at ECN sites, representing partial recovery from acidification. Overall, therefore, ECN sites have experienced marked changes in atmospheric chemistry and weather regimes over the last two decades that might be expected to have exerted detectable effects on ecosystem structure and function. While the downward trend in acid deposition is unlikely to be reversed, it is too early to conclude whether the trend towards wetter summers simply represents a phase in a multi-decadal cycle, or is indicative of a more directional shift in climate. Conversely, the first two decades of ECN now provide a relatively stable long-term baseline with respect to air temperature, against which effects of anticipated future warming on these ecosystems should be able to be assessed robustly

Copernicus Cal/Val Solution - D3.1 Recommendations for R&D activities on Instrumentation Technologies

The Document identifies the gaps in instrumentation technologies for pre-flight characterisation, onboard calibration and Fiducial Reference Measurements (FRM) used for calibration and validation (Cal/Val) activities for the current Copernicus missions. It also addresses the measurement needs for future Copernicus missions and gives a prioritised list of recommendations for R&D activities on instrumentation technologies. Four types of missions are covered based on the division used in the rest of the CCVS project: optical, altimetry, radar and microwave and atmospheric composition. It also gives an overview of some promising instrumentation technologies in each measurement field for FRM that could fill the gaps for requirements not yet met for the current and future Copernicus missions and identifies the research and development (R&D) activities needed to mature these example technologies. The Document does not provide an exhaustive list of all the new technologies being developed but will give a few examples for each field to show what efforts are being made to fill the gaps. None of the examples is promoted as the best possible solutions. The selection is based on the authors' knowledge during the preparation of the Document. The information included is mainly collected from the deliverables of work packages 1 and 2 in the CCVS project. The new technologies are primarily from the interviews with various measurement networks and campaigns carried out in tasks 2.4 and 2.5. Reference documents can be found in section 1.3

Resilience of benthic deep-sea fauna to mining activities

With increasing demand for mineral resources, extraction of polymetallic sulphides at hydrothermal vents, cobalt-rich ferromanganese crusts at seamounts, and polymetallic nodules on abyssal plains may be imminent. Here, we shortly introduce ecosystem characteristics of mining areas, report on recent mining developments, and identify potential stress and disturbances created by mining. We analyze species' potential resistance to future mining and perform meta-analyses on population density and diversity recovery after disturbances most similar to mining: volcanic eruptions at vents, fisheries on seamounts, and experiments that mimic nodule mining on abyssal plains. We report wide variation in recovery rates among taxa, size, and mobility of fauna. While densities and diversities of some taxa can recover to or even exceed pre-disturbance levels, community composition remains affected after decades. The loss of hard substrata or alteration of substrata composition may cause substantial community shifts that persist over geological timescales at mined sites. (C) 2017 Elsevier Ltd. All rights reserved.European Union Seventh Framework Programme (FP7) under the MIDAS project; FCT [IF/00029/2014/CP1230/CT0002, SFRH/ BPD/110278/2015]; Spanish RTD project NUREIEV [CTM2013-44598-R]; Ministry of Economy and Competitiveness [SGR 1068]; Generalitat de Catalunya autonomous government; European Union Horizon research and innovation programme [689518]; Fundacao para a Ciencia e a Tecnologia [UID/MAR/04292/2013]; German Ministry of Research (BMBF) [03F0707A-G]; Program Investigador FCT [IF/01194/2013/CP1199/CT0002]info:eu-repo/semantics/publishedVersio