Sharing of heteroplasmies between human liver lobes varies across the mtDNA genome

Mitochondrial DNA (mtDNA) heteroplasmy (intra-individual variation) varies among different human tissues and increases with age, suggesting that the majority of mtDNA heteroplasmies are acquired, rather than inherited. However, the extent to which heteroplasmic sites are shared across a tissue remains an open question. We therefore investigated heteroplasmy in two liver samples (one from each primary lobe) from 83 Europeans, sampled at autopsy. Minor allele frequencies (MAF) at heteroplasmic sites were significantly correlated between the two liver samples from an individual, with significantly more sharing of heteroplasmic sites in the control region than in the non-control region. We show that this increased sharing for the control region cannot be explained by recent mutations at just a few specific heteroplasmic sites or by the possible presence of 7S DNA. Moreover, we carried out simulations to show that there is significantly more sharing than would be predicted from random genetic drift from a common progenitor cell. We also observe a significant excess of non-synonymous vs. synonymous heteroplasmies in the protein-coding region, but significantly more sharing of synonymous heteroplasmies. These contrasting patterns for the control vs. the non-control region, and for non-synonymous vs. synonymous heteroplasmies, suggest that selection plays a role in heteroplasmy sharing

Accommodation coefficient of HOBr on deliquescent sodium bromide aerosol particles

Uptake of HOBr on sea salt aerosol, sea salt brine or ice is believed to be a key process providing a source of photolabile bromine (Br₂) and sustaining ozone depletion cycles in the Arctic troposphere. In the present study, uptake of HOBr on sodium bromide (NaBr) aerosol particles was investigated at an extremely low HOBr concentration of 300 cm^-3 using the short-lived radioactive isotopes ^83-86Br. Under these conditions, at maximum one HOBr molecule was taken up per particle. The rate of uptake was clearly limited by the mass accommodation coefficient, which was calculated to be 0.6 ± 0.2. This value is a factor of 10 larger than estimates used in earlier models. The atmospheric implications are discussed using the box model "MOCCA'', showing that the increase of the accommodation coefficient of HOBr by a factor of 10 only slightly affects net ozone loss, but significantly increases chlorine release

Increase in degraded collagen type II in synovial fluid early in the rabbit meniscectomy model of osteoarthritis

SummaryObjectiveThe objective of this study was to determine whether collagen type II breakdown products in synovial fluid (SF), detected by an enzyme-linked immunoassay, represent a useful marker for early events in osteoarthritis (OA) in the rabbit medial meniscectomy model.DesignComplete medial meniscectomy was performed on the right knee joints of 32 rabbits. Balanced groups of rabbits were then sacrificed at 2, 4, 8, and 12 weeks post-surgery. An additional 8 unoperated and 11 sham-operated animals served as controls. SF lavages were performed on right and left knee joints of the same animals at sacrifice. The proteolytic epitope of type II collagen was monitored using an enzyme-linked immunoassay.ResultsMacroscopically visible surface fibrillation and focal erosions appeared as early as 2 weeks after meniscectomy in the femorotibial joint (P<0.01). OA developed gradually during the later observation period, and then predominantly on the medial tibial plateau and medial femur. Significant histological alterations in cartilage, including a loss of proteoglycans, surface irregularities, and clefts, were detected at 2 weeks after meniscectomy (P<0.01). Collagen type II epitope levels in SF lavage samples were elevated peaking at 2 weeks after meniscectomy (P<0.02). Levels decreased at later time points, but they were still raised at 12 weeks (P≤0.05). Highly significant correlations were found between the SF collagen type II epitope levels and the macroscopic and microscopic scoring results (Spearman rho correlation coefficient, macroscopy—collagen type II epitope r=0.222, P=0.025; microscopy—collagen type II epitope r=0.436, P≤0.01).ConclusionIn this rabbit model of medial meniscectomy, levels of type II collagen fragments in SF appear to provide a useful marker of the early degenerative changes

What changed your mind : the roles of dynamic topics and discourse in argumentation process

In our world with full of uncertainty, debates and argumentation contribute to the progress of science and society. Despite of the in- creasing attention to characterize human arguments, most progress made so far focus on the debate outcome, largely ignoring the dynamic patterns in argumentation processes. This paper presents a study that automatically analyzes the key factors in argument persuasiveness, beyond simply predicting who will persuade whom. Specifically, we propose a novel neural model that is able to dynamically track the changes of latent topics and discourse in argumentative conversations, allowing the investigation of their roles in influencing the outcomes of persuasion. Extensive experiments have been conducted on argumentative conversations on both social media and supreme court. The results show that our model outperforms state-of-the-art models in identifying persuasive arguments via explicitly exploring dynamic factors of topic and discourse. We further analyze the effects of topics and discourse on persuasiveness, and find that they are both useful -- topics provide concrete evidence while superior discourse styles may bias participants, especially in social media arguments. In addition, we draw some findings from our empirical results, which will help people better engage in future persuasive conversations

Probing microscopic origins of confined subdiffusion by first-passage observables

Subdiffusive motion of tracer particles in complex crowded environments, such as biological cells, has been shown to be widepsread. This deviation from brownian motion is usually characterized by a sublinear time dependence of the mean square displacement (MSD). However, subdiffusive behavior can stem from different microscopic scenarios, which can not be identified solely by the MSD data. In this paper we present a theoretical framework which permits to calculate analytically first-passage observables (mean first-passage times, splitting probabilities and occupation times distributions) in disordered media in any dimensions. This analysis is applied to two representative microscopic models of subdiffusion: continuous-time random walks with heavy tailed waiting times, and diffusion on fractals. Our results show that first-passage observables provide tools to unambiguously discriminate between the two possible microscopic scenarios of subdiffusion. Moreover we suggest experiments based on first-passage observables which could help in determining the origin of subdiffusion in complex media such as living cells, and discuss the implications of anomalous transport to reaction kinetics in cells.Comment: 21 pages, 3 figures. Submitted versio

Antibiotic resistance in Enterotoxigenic and non-enterotoxigenic Escherichia coli.

Antibiotic disk susceptibility tests were done on 220 strains of Escherichia coli belonging to serotypes reported in the literature to be associated with the production of enterotoxin. A total of 128 (58%) were resistant to one or more antibiotics, sulfa drugs, or chemotherapeutic agents. An analysis of these strains revealed primary, secondary, and tertiary drug resistance patterns that indicated a selective pattern in the formation of multiple drug resistance in E. coli. Resistances to certain antibiotics were more likely to occur in pairs and triads (secondary resistance patterns) that were often combined or coexisted in a single strain of E. coli to produce tertiary drug resistance patterns, conferring drug resistance to five or six different antibiotics. Among enterotoxin-associated serotypes, single and multiple drug resistance was less frequently associated with enterotoxin-produced strains than with strains from the same serotype that were not enterotoxigenic. Within the enterotoxigenic E. coli, single and multiple resistance to antibiotics was more frequent in strains producing only heat-stable enterotoxin (ST) than in strains producing only heat-labile enterotoxin (LT) or both. The number of resistances to different antibiotics per resistant strain averaged approximately 1.4 for LT plus ST or LT strains, and 3.9 for ST strains and nonenterotoxigenic strains. Phenotypic characterization of 170 strains for four usually plasmid-mediated characteristics showed that the number of antibiotics to which a strain was directly resistant varied with the type and number of plasmid-mediated characteristics present

Using standard typing algorithms incrementally

Modern languages are equipped with static type checking/inference that helps programmers to keep a clean programming style and to reduce errors. However, the ever-growing size of programs and their continuous evolution require building fast and efficient analysers. A promising solution is incrementality, aiming at only re-typing the diffs, i.e. those parts of the program that change or are inserted, rather than the entire codebase. We propose an algorithmic schema that drives an incremental usage of existing, standard typing algorithms with no changes. Ours is a grey-box approach: just the shape of the input, that of the results and some domain-specific knowledge are needed to instantiate our schema. Here, we present the foundations of our approach and the conditions for its correctmess. We show it at work to derive two different incremental typing algorithms. The first type checks an imperative language to detect information flow and non-interference, and the second infers types for a functional language. We assessed our proposal on a prototypical imple- mentation of an incremental type checker. Our experiments show that using the type checker incrementally is (almost) always rewardin

Using Standard Typing Algorithms Incrementally

Modern languages are equipped with static type checking/inference that helps programmers to keep a clean programming style and to reduce errors. However, the ever-growing size of programs and their continuous evolution require building fast and efficient analysers. A promising solution is incrementality, so one only re-types those parts of the program that are new, rather than the entire codebase. We propose an algorithmic schema driving the definition of an incremental typing algorithm that exploits the existing, standard ones with no changes. Ours is a grey-box approach, meaning that just the shape of the input, that of the results and some domain-specific knowledge are needed to instantiate our schema. Here, we present the foundations of our approach and we show it at work to derive three different incremental typing algorithms. The first two implement type checking and inference for a functional language. The last one type-checks an imperative language to detect information flow and non-interference. We assessed our proposal on a prototypical implementation of an incremental type checker. Our experiments show that using the type checker incrementally is (almost) always rewarding.Comment: corrected and updated; experimental results adde