773 research outputs found
Virus-mediated EpoR76E gene therapy preserves vision in a glaucoma model by modulating neuroinflammation and decreasing oxidative stress
Flow graphs: interweaving dynamics and structure
The behavior of complex systems is determined not only by the topological
organization of their interconnections but also by the dynamical processes
taking place among their constituents. A faithful modeling of the dynamics is
essential because different dynamical processes may be affected very
differently by network topology. A full characterization of such systems thus
requires a formalization that encompasses both aspects simultaneously, rather
than relying only on the topological adjacency matrix. To achieve this, we
introduce the concept of flow graphs, namely weighted networks where dynamical
flows are embedded into the link weights. Flow graphs provide an integrated
representation of the structure and dynamics of the system, which can then be
analyzed with standard tools from network theory. Conversely, a structural
network feature of our choice can also be used as the basis for the
construction of a flow graph that will then encompass a dynamics biased by such
a feature. We illustrate the ideas by focusing on the mathematical properties
of generic linear processes on complex networks that can be represented as
biased random walks and also explore their dual consensus dynamics.Comment: 4 pages, 1 figur
Cost-Optimal Planning, Delete Relaxation, Approximability, and Heuristics
Cost-optimal planning is a very well-studied topic within planning, and it has proven to be computationally hard both in theory and in practice. Since cost-optimal planning is an optimisation problem, it is natural to analyse it through the lens of approximation. An important reason for studying cost-optimal planning is heuristic search; heuristic functions that guide the search in planning can often be viewed as algorithms solving or approximating certain optimisation problems. Many heuristic functions (such as the ubiquitious h+ heuristic) are based on delete relaxation, which ignores negative effects of actions. Planning for instances where the actions have no negative effects is often referred to as monotone planning. The aim of this article is to analyse the approximability of cost-optimal monotone planning, and thus the performance of relevant heuristic functions. Our findings imply that it may be beneficial to study these kind of problems within the framework of parameterised complexity and we initiate work in this direction
Grappling with the social dimensions of novel ecosystems
The novel ecosystem concept has emerged in response to the increasing prevalence of modified ecosystems. Traditional conservation and restoration strategies have been deemed inadequate to guide the management of ecosystems that are the product of anthropogenic environmental change and have no ânaturalâ analogs. Opinions about novel ecosystems are currently divided between those who embrace the flexibility offered by the concept and those who see it as a shift toward the abandonment of traditional strategies. However, the debate is missing a key element: recognition that all conservation decisions are socially constructed and that the concept of novel ecosystems is most practicable within a decision or management context. Management of novel ecosystems should be framed in such a context, and the concept evaluated for its capacity to meet social, ecological, and economic objectives
Active Re-identification Attacks on Periodically Released Dynamic Social Graphs
Active re-identification attacks pose a serious threat to privacy-preserving
social graph publication. Active attackers create fake accounts to build
structural patterns in social graphs which can be used to re-identify
legitimate users on published anonymised graphs, even without additional
background knowledge. So far, this type of attacks has only been studied in the
scenario where the inherently dynamic social graph is published once. In this
paper, we present the first active re-identification attack in the more
realistic scenario where a dynamic social graph is periodically published. The
new attack leverages tempo-structural patterns for strengthening the adversary.
Through a comprehensive set of experiments on real-life and synthetic dynamic
social graphs, we show that our new attack substantially outperforms the most
effective static active attack in the literature by increasing the success
probability of re-identification by more than two times and efficiency by
almost 10 times. Moreover, unlike the static attack, our new attack is able to
remain at the same level of effectiveness and efficiency as the publication
process advances. We conduct a study on the factors that may thwart our new
attack, which can help design graph anonymising methods with a better balance
between privacy and utility
Resonant two-phonon Raman scattering as a probe of hole crystal formation in Sr14-xCaxCu24O41
General lack of global dosage compensation in ZZ/ZW systems? Broadening the perspective with RNA-seq
Background
Species with heteromorphic sex chromosomes face the challenge of large-scale imbalance in gene dose. Microarray-based studies in several independent male heterogametic XX/XY systems suggest that dosage compensation mechanisms are in place to mitigate the detrimental effects of gene dose differences. However, recent genomic research on female heterogametic ZZ/ZW systems has generated surprising results. In two bird species and one lepidopteran no evidence for a global dosage compensating mechanism has been found. The recent advent of massively parallel RNA sequencing now opens up the possibility to gauge the generality of this observation with a broader phylogenetic sampling. It further allows assessing the validity of microarray-based inference on dosage compensation with a novel technology.
Results
We here expemplify this approach using massively parallel sequencing on barcoded individuals of a bird species, the European crow (Corvus corone), where previously no genetic resources were available. Testing for Z-linkage with quantitative PCR (qPCR,) we first establish that orthology with distantly related species (chicken, zebra finch) can be used as a good predictor for chromosomal affiliation of a gene. We then use a digital measure of gene expression (RNA-seq) on brain transcriptome and confirm a global lack of dosage compensation on the Z chromosome. RNA-seq estimates of male-to-female (m:f) expression difference on the Z compare well to previous microarray-based estimates in birds and lepidopterans. The data further lends support that an up-regulation of female Z-linked genes conveys partial compensation and suggest a relationship between sex-bias and absolute expression level of a gene. Correlation of sex-biased gene expression on the Z chromosome across all three bird species further suggests that the degree of compensation has been partly conserved across 100 million years of avian evolution.
Conclusions
This work demonstrates that the study of dosage compensation has become amenable to species where previously no genetic resources were available. Massively parallele transcriptome sequencing allows re-assessing the degree of dosage compensation with a novel tool in well-studies species and, in addition, gain valuable insights into the generality of mechanisms across independent taxonomic group for both the XX/XY and ZZ/ZW system
Circadian hormone secretory profiles in women with severe premenstrual tension syndrome.
The circadian secretory profiles of serum prolactin, growth hormone and cortisol were measured in two women suffering from severe premenstrual tension syndrome and in two asymptomatic control subjects. Subjects and controls were screened and included after a rigorous selection process. Blood samples were obtained every 30 min over a period of 24 h in each woman both on day 9 (follicular phase) and day 26 (luteal phase) of the menstrual cycle. There was no relationship between the hormonal secretory profiles and the premenstrual tension syndrome.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75119/1/j.1471-0528.1984.tb04785.x.pd
Health-related quality of life in patients with ÎČ-thalassemia: Data from the phase 3 BELIEVE trial of luspatercept
BACKGROUND: Patients with transfusion-dependent (TD) ÎČ-thalassemia require long-term red blood cell transfusions (RBCTs) that lead to iron overload, impacting health-related quality of life (HRQoL). METHODS: The impact of luspatercept, a first-in-class erythroid maturation agent, versus placebo on HRQoL of patients with TD ÎČ-thalassemia was evaluated in the phase 3 BELIEVE trial. HRQoL was assessed at baseline and every 12âweeks using the 36-item Short Form Health Survey (SF-36) and Transfusion-dependent Quality of Life questionnaire (TranQol). Mean change in HRQoL was evaluated from baseline to week 48 for patients receiving luspatercept + best supportive care (BSC) and placebo + BSC and between luspatercept responders and non-responders. RESULTS: Through week 48, for both groups, mean scores on SF-36 and TranQol domains were stable over time and did not have a clinically meaningful change. At week 48, more patients who achieved clinical response (â„50% reduction in RBCT burden over 24âweeks) in the luspatercept + BSC group had improvement in SF-36 Physical Function compared with placebo + BSC (27.1% vs. 11.5%; pâ=â.019). CONCLUSIONS: Luspatercept + BSC reduced transfusion burden while maintaining patients' HRQoL. HRQoL domain improvements from baseline through 48âweeks were also enhanced for luspatercept responders
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