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Multiple ionic memories in asymmetric nanochannels revealed by mem-spectrometry
No full textRecently discovered nanofluidic memristors, have raised promises for the development of iontronics and neuromorphic computing with ions. Ionic memory effects are related to ion dynamics inside nanochannels, with timescales associated with the manifold physicochemical phenomena occurring at confined interfaces. Here, we explore experimentally the frequency-dependent current–voltage response of model nanochannels—namely glass nanopipettes—to investigate memory effects in ion transport. This characterisation, which we refer to as mem-spectrometry, highlights two characteristic frequencies, associated with short and long timescales of the order of 50 ms and 50 s in the present system. Whereas the former can be associated with ionic diffusion, very long timescales are difficult to explain with conventional transport phenomena. We develop a minimal model accounting for these mem-spectrometry results, pointing to surface charge regulation and ionic adsorption-desorption as possible origins for the long-term memory. Our work demonstrates the relevance of mem-spectrometry to highlight subtle ion transport properties in nanochannels, giving hereby new insights on the mechanisms governing ion transport and current rectification in charged conical nanopores
Cooperative software verification via dynamic program splitting
No full textCooperative software verification divides the task of software verification among several verification tools in order to increase efficiency and effectiveness. The basic approach is to let verifiers work on different parts of a program and at the end join verification results. While this idea is intuitively appealing, cooperative verification is usually hindered by the fact that program decomposition (1) is often static, disregarding strengths and weaknesses of employed verifiers, and (2) often represents the decomposed program parts in a specific proprietary format, thereby making the use of off-the-shelf verifiers in cooperative verification difficult. In this paper, we propose a novel cooperative verification scheme that we call dynamic program splitting (DPS). Splitting decomposes programs into (smaller) programs, and thus directly enables the use of off-the-shelf tools. In DPS, splitting is dynamically applied on demand: Verification starts by giving a verification task (a program plus a correctness specification) to a verifier V1. Whenever V1 finds the current task to be hard to verify, it splits the task (i.e., the program) and restarts verification on subtasks. DPS continues until (1) a violation is found, (2) all subtasks are completed or (3) some user-defined stopping criterion is met. In the latter case, the remaining uncompleted subtasks are merged into a single one and are given to a next verifier V2, repeating the same procedure on the still unverified program parts. This way, the decomposition is steered by what is hard to verify for particular verifiers, leveraging their complementary strengths. We have implemented dynamic program splitting and evaluated it on benchmarks of the annual software verification competition SV-COMP. The evaluation shows that cooperative verification with DPS is able to solve verification tasks that none of the constituent verifiers can solve, without any significant overhead
LINC01638 promotes epithelial-to-mesenchymal transition in endometriosis epithelial cells by up-regulating RHOB via HDAC1 suppression
No full textResearch question: Is LINC01638 involved in regulation of epithelial-to-mesenchymal transition (EMT) in endometriosis?
Design: A prospective patient cohort study was combined with functional experiments in the 12Z endometriosis epithelial cell line to investigate the role of LINC01638 in endometriosis. Eutopic endometrial samples were collected by curettage, and ectopic endometrial lesion samples were collected by laparoscopic surgery from 24 control patients and 41 patients with endometriosis. The phenotype of 12Z cells was assessed following LINC01638 knockdown using siRNA, performing proliferation, adhesion, migration and invasion assays, as well as assessing apoptosis and cell cycle changes with flow cytometry assays. In order to assess the relationship between LINC01638 and histone deacetylase class 1 enzyme (HDAC1), LINC01638 knockdown was combined with HDAC inhibition with the specific HDAC inhibitor romidepsin.
Results: LINC01638 was up-regulated in the epithelial layer of endometriotic lesions, and LINC01638 knockdown in 12Z cells led to reduced proliferation, adhesion, migration and invasion. The reduction in proliferation was associated with increased p21 and p27 expression, and G1 phase arrest. Further analysis of LINC01638 control and knockdown cells revealed that a number of transcription factors associated with EMT are down-regulated in knockdown cells, along with the cytoskeleton regulatory gene RHOB, while HDAC1 was up-regulated. Chromatin immunoprecipitation analysis and HDAC1 inhibitory treatment combined with LINC01638 knockdown indicated that LINC01638 regulates RHOB expression via HDAC1-mediated promoter deacetylation. RHOB is up-regulated in the epithelial layer of endometriotic lesions compared with eutopic endometrium, supporting a role in the disease.
Conclusions: LINC01638 is an epigenetic regulator of the pathogenesis of endometriosis, promoting proliferation and EMT of endometriotic lesions
LNCS
No full textIn this work, we explore route discovery in private payment channel networks. We first determine what “ideal" privacy for a routing protocol means in this setting. We observe that protocols achieving this strong privacy definition exist by leveraging Multi-Party Computation but they are inherently inefficient as they must involve the entire network. We then present protocols with weaker privacy guarantees but much better efficiency (involving only a small fraction of the nodes). The core idea is that both sender and receiver gossip a message which propagates through the network, and the moment any node in the network receives both messages, a path is found. In our first protocol the message is always sent to all neighbouring nodes with a delay proportional to the fees of that edge. In our second protocol the message is only sent to one neighbour chosen randomly with a probability proportional to its degree. We additionally propose a more realistic notion of privacy in order to measure the privacy leakage of our protocols in practice. Our realistic notion of privacy challenges an adversary that join the network with a fixed budget to create channels to guess the sender and receiver of a transaction upon receiving messages from our protocols. Simulations of our protocols on the Lightning network topology (for random transactions and uniform fees) show that 1) forming edges with high degree nodes is a more effective attack strategy for the adversary, 2) there is a tradeoff between the number of nodes involved in our protocols (privacy) and the optimality of the discovered path, and 3) our protocols involve a very small fraction of the network on average
Research Data for the publication "Super-resolution expansion microscopy in plant roots"
No full textSuper-resolution methods provide far better spatial resolution than the optical diffraction limit of about half the wavelength of light (∼200-300 nm). Nevertheless, they have yet to attain widespread use in plants, largely due to plants’ challenging optical properties. Expansion microscopy improves effective resolution by isotropically increasing the physical distances between sample structures while preserving relative spatial arrangements and clearing the sample. However, its application to plants has been hindered by the rigid, mechanically cohesive structure of plant tissues. Here, we report on whole-mount expansion microscopy of thale cress (Arabidopsis thaliana) root tissues (PlantEx), achieving a four-fold resolution increase over conventional microscopy. Our results highlight the microtubule cytoskeleton organization and interaction between molecularly defined cellular constituents. Combining PlantEx with stimulated emission depletion (STED) microscopy, we increase nanoscale resolution and visualize the complex organization of subcellular organelles from intact tissues by example of the densely packed COPI-coated vesicles associated with the Golgi apparatus and put these into a cellular structural context. Our results show that expansion microscopy can be applied to increase effective imaging resolution in Arabidopsis root specimens
Fairness shields: Safeguarding against biased decision makers
No full textAs AI-based decision-makers increasingly influence human lives, it is a growing concern that their decisions may be unfair or biased with respect to people's protected attributes, such as gender and race. Most existing bias prevention measures provide probabilistic fairness guarantees in the long run, and it is possible that the decisions are biased on any decision sequence of fixed length. We introduce *fairness shielding*, where a symbolic decision-maker---the fairness shield---continuously monitors the sequence of decisions of another deployed black-box decision-maker, and makes interventions so that a given fairness criterion is met while the total intervention costs are minimized. We present four different algorithms for computing fairness shields, among which one guarantees fairness over fixed horizons, and three guarantee fairness periodically after fixed intervals. Given a distribution over future decisions and their intervention costs, our algorithms solve different instances of bounded-horizon optimal control problems with different levels of computational costs and optimality guarantees. Our empirical evaluation demonstrates the effectiveness of these shields in ensuring fairness while maintaining cost efficiency across various scenarios
Identification and inhibition of PIN1-NRF2 protein–protein interactions through computational and biophysical approaches
No full textNRF2 is a transcription factor responsible for coordinating the expression of over a thousand cytoprotective genes. Although NRF2 is constitutively expressed, its stability is modulated by the redox-sensitive protein KEAP1 and other conditional binding partner regulators. The new era of NRF2 research has highlighted the cooperation between NRF2 and PIN1 in modifying its cytoprotective effect. Despite numerous studies, the understanding of the PIN1-NRF2 interaction remains limited. Herein, we described the binding interaction of PIN1 and three different 14-mer long phospho-peptides mimicking NRF2 protein using computer-based, biophysical, and biochemical approaches. According to our computational analyses, the residues positioned in the WW domain of PIN1 (Ser16, Arg17, Ser18, Tyr23, Ser32, Gln33, and Trp34) were found to be crucial for PIN1-NRF2 interactions. Biophysical FP assays were used to verify the computational prediction. The data demonstrated that Pintide, a peptide predominantly interacting with the PIN1 WW-domain, led to a significant reduction in the binding affinity of the NRF2 mimicking peptides. Moreover, we evaluated the impact of known PIN1 inhibitors (juglone, KPT-6566, and EGCG) on the PIN1-NRF2 interaction. Among the inhibitors, KPT-6566 showed the most potent inhibitory effect on PIN1-NRF2 interaction within an IC50 range of 0.3–1.4 µM. Furthermore, our mass spectrometry analyses showed that KPT-6566 appeared to covalently modify PIN1 via conjugate addition, rather than disulfide exchange of the sulfonyl-acetate moiety. Altogether, such inhibitors would also be highly valuable molecular probes for further investigation of PIN1 regulation of NRF2 in the cellular context and potentially pave the way for drug molecules that specifically inhibit the cytoprotective effects of NRF2 in cancer
Feigenbaum universality in subcritical Taylor-Couette flow
No full textFeigenbaum universality is shown to occur in subcritical shear flows. Our testing ground is the counter-rotation regime of the Taylor–Couette flow, where numerical calculations are performed within a small periodic domain. The accurate computation of up to the seventh period-doubling bifurcation, assisted by a purposely defined Poincaré section, has enabled us to reproduce the two Feigenbaum universal constants with unprecedented accuracy in a fluid flow problem. We have further devised a method to predict the bifurcation diagram up to the accumulation point of the cascade based on the detailed inspection of just the first few period-doubling bifurcations. Remarkably, the method is applicable beyond the accumulation point, with predictions remaining valid, in a statistical sense, for the chaotic dynamics that follows
Snow line altitude in high mountain Asia derived from satellite imagery (LS5, LS7, LS8 & S2) between 1999 and 2019
No full textThis repository contains the data used for the study Precipitation phase drives seasonal and decadal snowline changes in high mountain Asia.
This study focuses on 4776 glacierized catchments across high mountain Asia (HMA). They are numbered from 0 to 4775. This code number is then used in all the products as their unique ID
Extensive N4 cytosine methylation is essential for Marchantia sperm function
No full textN4-methylcytosine (4mC) is an important DNA modification in prokaryotes, but its relevance and even its presence in eukaryotes have been mysterious. Here we show that spermatogenesis in the liverwort Marchantia polymorpha involves two waves of extensive DNA methylation reprogramming. First, 5-methylcytosine (5mC) expands from transposons to the entire genome. Notably, the second wave installs 4mC throughout genic regions, covering over 50% of CG sites in sperm. 4mC requires a methyltransferase (MpDN4MT1a) that is specifically expressed during late spermiogenesis. Deletion of MpDN4MT1a alters the sperm transcriptome, causes sperm swimming and fertility defects, and impairs post-fertilization development. Our results reveal extensive 4mC in a eukaryote, identify a family of eukaryotic methyltransferases, and elucidate the biological functions of 4mC in reproductive development, thereby expanding the repertoire of functional eukaryotic DNA modifications