Motion control and synchronisation of multi-axis drive systems

Motion control and synchronisation of multi-axis drive system

Differential Disruption of EWS-FLI1 Binding by DNA-Binding Agents

Fusion of the EWS gene to FLI1 produces a fusion oncoprotein that drives an aberrant gene expression program responsible for the development of Ewing sarcoma. We used a homogenous proximity assay to screen for compounds that disrupt the binding of EWS-FLI1 to its cognate DNA targets. A number of DNA-binding chemotherapeutic agents were found to non-specifically disrupt protein binding to DNA. In contrast, actinomycin D was found to preferentially disrupt EWS-FLI1 binding by comparison to p53 binding to their respective cognate DNA targets in vitro. In cell-based assays, low concentrations of actinomycin D preferentially blocked EWS-FLI1 binding to chromatin, and disrupted EWS-FLI1-mediated gene expression. Higher concentrations of actinomycin D globally repressed transcription. These results demonstrate that actinomycin D preferentially disrupts EWS-FLI1 binding to DNA at selected concentrations. Although the window between this preferential effect and global suppression is too narrow to exploit in a therapeutic manner, these results suggest that base-preferences may be exploited to find DNA-binding compounds that preferentially disrupt subclasses of transcription factors

Improved Multi-User Security Using the Squared-Ratio Method

Proving security bounds in contexts with a large number of users is one of the central problems in symmetric-key cryptography today. This paper introduces a new method for information-theoretic multi-user security proofs, called ``the Squared-Ratio Method\u27\u27. At its core, the method requires the expectation of the square of the ratio of observing the so-called good transcripts (from Patarin\u27s H-coefficient technique) in the real and the ideal world. Central to the method is the observation that for information-theoretic adversaries, the KL-divergence for the multi-user security bound can be written as a summation of the KL-divergence of every single user. We showcase the Squared-Ratio Method on three examples: the Xor of two Permutations by Bellare et al. (EUROCRYPT \u2798) and Hall et al. (CRYPTO \u2798), the Encrypted Davies-Mayer by Cogliati and Seurin (CRYPTO \u2716), and the two permutation variant of the nEHtM MAC algorithm by Dutta et al. (EUROCRYPT \u2719). With this new tool, we provide improved bounds for the multi-user security of these constructions. Our approach is modular in the sense that the multi-user security can be obtained directly from single-user results

The role of receptor dimerization domain residues in growth hormone signaling

While there is a considerable amount of evidence that signal transduction by the growth hormone (GH) receptor requires receptor homodimerization, there has been no systematic study of the role of receptor dimerization domain residues in this process, In conjunction with the distances derived from the crystal structure of the hGH-hGH receptor (extracellular domain) complex, we have used a luciferase based c-fos promoter reporter assay in transiently transfected Chinese hamster ovary (CHO) cells, and stable receptor expressing CHO cell populations to define the dimerization domain residues needed for effective signaling, In addition to alanine substitution, we have used both aspartate and lysine substitutions to allow us to provide evidence for proximity relations through charge complementation. Introduced cysteine substitutions were also used, but unlike the erythropoietin receptor, these were unable to generate constitutively active receptor, We conclude that serine 145, histidine 150, aspartate 152, tyrosine 200, and serine 201, but not leucine 146 or threonine 147 are required for effective signal transduction through the dimerization domain, This information may be valuable in designing small molecule antagonists of GH and other cytokines that block dimerization by binding to the dimerization domain

Central 300 PC of the galaxy probed by the infrared spectra of H3+ and CO: I. Predominance of warm and diffuse gas and high H2 ionization rate

A low-resolution 2.0-2.5 $\mu$m survey of $\sim$500 very red point-like objects in the Central Molecular Zone (CMZ) of our Galaxy, initiated in 2008, has revealed many new bright objects with featureless spectra that are suitable for high resolution absorption spectroscopy of H$_3^+$ and CO.\footnote{Geballe, T. R., Oka, T., Lambridges, E., Yeh, S. C. C., Schlegelmilch, B., Goto, M., Westrick, C. W., WI07 at the 70th ISMS, Urbana, IL, USA,2015} We now have altogether 48 objects mostly close to the Galactic plane located from 142 pc to the west of Sgr A to 120 pc east allowing us to probe dense and diffuse gas by H$_3^+$ and dense gas by CO. Our observations demonstrate that the warm ($\sim$250 K) and diffuse ($\leq$100 cm$^{-3}$) gas with a large column length ($\geq$30 pc) initially observed toward the brightest star in the CMZ, GCS3-2 of the Quintuplet Cluster,\footnote{Oka, T., Geballe, T. R., Goto, M., Usuda, T., McCall, B. J. 2005, ApJ, 632, 882} exists throughout the CMZ with the surface filling factor of $\sim$ 100\% dominating the region. The column densities of CO in the CMZ are found to be much less than those in the three foreground spiral arms except in the directions of Sgr B and Sgr E complexes and indicate that the volume filling factor of dense clouds of 10\% previously estimated is a gross overestimate for the front half of the CMZ. Nevertheless the predominance of the newly found diffuse molecular gas makes the term "Central Molecular Zone" even more appropriate. The ultra-hot X-rays emitting plasma which some thought to dominate the region must be non existent except near the stars and SNRs. Recently the H$_2$ fraction $\mathit{f}$(H$_2$) in diffuse gas of the CMZ has been reported to be $\sim$0.6\footnote{Le Petit, F., Ruaud, M., Bron, E., Godard, B., Roueff, E., Languignon, D., Le Bourlot, J. 2016, A\&A, 585, A105}. If we use this value, the cosmic ray H$_2$ ionization rate $\mathit{\zeta}$ of a few times 10$^{-15}$ s$^{-1}$ reported earlier$^b$ on the assumption of $\mathit{f}$(H$_2$)=1 needs to be increased by a factor of $\sim$3 since the value is approximately inversely proportional to $\mathit{f}$(H$_2$)$^2$

Observation of three-state nematicity in the triangular lattice antiferromagnet Fe1/3_{1/3} NbS2_2

Nematic order is the breaking of rotational symmetry in the presence of translational invariance. While originally defined in the context of liquid crystals, the concept of nematic order has arisen in crystalline matter with discrete rotational symmetry, most prominently in the tetragonal Fe-based superconductors where the parent state is four-fold symmetric. In this case the nematic director takes on only two directions, and the order parameter in such "Ising-nematic" systems is a simple scalar. Here, using a novel spatially-resolved optical polarimetry technique, we show that a qualitatively distinct nematic state arises in the triangular lattice antiferromagnet Fe$_{1/3}$NbS$_2$. The crucial difference is that the nematic order on the triangular lattice is a Z$_3$, or three-state Potts-nematic order parameter. As a consequence, the anisotropy axes of response functions such as the resistivity tensor can be continuously re-oriented by external perturbations. This discovery provides insight into realizing devices that exploit analogies with nematic liquid crystals.Comment: The main text is 16 pages, including 5 figures and references. Supplementary information is appended at the end of the articl

Multi-omics reveals the alleviating effect of berberine on ulcerative colitis through modulating the gut microbiome and bile acid metabolism in the gut-liver axis

The dysfunction of gut microbiome and bile acid metabolism might cause the incidence and relapse of ulcerative colitis (UC). Thus, natural products have been considered effective for UC through the regulation of gut microbiome and bile acid. In this study, we evaluated the regulatory effect of berberine on gut microbiome and bile acid metabolism in UC. Results showed that the relative abundances of beneficial bacteria showed a decreasing trend in the UC model, and the taurine conjugated bile acids increased from the liver tissue to the colon tissue. Berberine inhibited the colonization of harmful bacteria and promoted the primary bile acid metabolism. Moreover, we used multi-omics technology (metagenomics, metabolomics, and transcriptomics technology) to reveal that berberine restored the intestinal barrier function through bile acid/S1PR2/RhoA/ROCK pathway. The result of transmission electron microscopy directly showed that the damaged intestinal mucosal barrier was repaired through the berberine treatment. This study revealed the treatment influence on UC through multi-omics technology in vitro and in vivo models, which provides references for explaining the mechanism of berberine on UC

Higher fibrinogen and neutrophil-to-lymphocyte ratio are associated with the early poor response to intravenous thrombolysis in acute ischemic stroke

BackgroundInflammation and platelet activation play pivotal roles in acute ischemic stroke (AIS) pathogenesis. Early response to thrombolysis is a vital indicator for the long-term prognosis of AIS. However, the correlation between fibrinogen or the neutrophil-to-lymphocyte ratio (NLR) and the early response to intravenous thrombolysis in patients with AIS remains unclear.MethodsAIS patients undergoing intravenous thrombolysis were enrolled between January 2018 and May 2023. Blood cell counts were sampled before thrombolysis. A good response was defined as a National Institutes of Health Stroke Scale (NIHSS) score decreased ≥4 or complete recovery 24 h after thrombolysis treatment. A poor response was defined as any increase in the NIHSS score or a decrease in the NIHSS score <4 at the 24 h after thrombolysis treatment compared with that at admission. Logistic regression analysis was performed to explore the relationship of the fibrinogen level and NLR with a poor thrombolysis response. Receiver operating characteristic (ROC) analysis was used to assess the ability of the fibrinogen level and NLR to discriminate poor responders.ResultsAmong 700 recruited patients, 268 (38.29%) were diagnosed with a good response, and 432 (61.71%) were diagnosed with a poor response to intravenous thrombolysis. A binary logistic regression model indicated that an elevated fibrinogen level (odds ratio [OR], 1.693; 95% confidence interval [CI] 1.325–2.122, P < 0.001) and NLR (OR, 1.253; 95% CI, 1.210–2.005, P = 0.001) were independent factors for a poor response. The area under the curve (AUC) values for the fibrinogen level, NLR and fibrinogen level combined with the NLR for a poor response were 0.708, 0.605, and 0.728, respectively.ConclusionsOur research indicates that the levels of fibrinogen and NLR at admission can be used as a prognostic factor to predict early poor response to intravenous thrombolysis

An atypical GdpP enzyme linking cyclic nucleotide metabolism to osmotic tolerance and gene regulation in Mycoplasma bovis

Nucleotide second messengers play an important role in bacterial adaptation to environmental changes. Recent evidence suggests that some of these regulatory molecular pathways were conserved upon the degenerative evolution of the wall-less mycoplasmas. We have recently reported the occurrence of a phosphodiesterase (PDE) in the ruminant pathogen Mycoplasma bovis, which was involved in c-di-AMP metabolism. In the present study, we demonstrate that the genome of this mycoplasma species encodes a PDE of the GdpP family with atypical DHH domains. Characterization of M. bovis GdpP (MbovGdpP) revealed a multifunctional PDE with unusual nanoRNase and single-stranded DNase activities. The alarmone ppGpp was found unable to inhibit c-di-NMP degradation by MbovGdpP but efficiently blocked its nanoRNase activity. Remarkably, MbovGdpP was found critical for the osmotic tolerance of M. bovis under K+ and Na+ conditions. Transcriptomic analyses further revealed the biological importance of MbovGdpP in tRNA biosynthesis, pyruvate metabolism, and several steps in genetic information processing. This study is an important step in understanding the role of PDE and nucleotide second messengers in the biology of a minimal bacterial pathogen