Miracle-dz/UniFAR-FTUs huggingface dataset:
FORK-1S: interactive compliant mechanisms with parallel state computation

We present a method for the simulation of compliant, articulated structures using a plausible approximate model that focuses on modeling endpoint interaction. We approximate the structure's behavior about a reference configuration, resulting in a first order reduced compliant system, or FORK-1S. Several levels of approximation are available depending on which parts and surfaces we would like to have interactive contact forces, allowing various levels of detail to be selected. Our approach is fast and computation of the full structure's state may be parallelized. Our approach is suitable for stiff, articulate grippers, such as those used in robotic simulation, or physics based characters under static proportional derivative control. We demonstrate that simulations with our method can deal with kinematic chains and loops with non-uniform stiffness across joints, and that it produces plausible effects due to stiffness, damping, and inertia.
Cyclooxygenase inhibitors increase Na-K-2Cl cotransporter abundance in thick ascending limb of Henle's loop.

Cyclooxygenase inhibitors, such as indomethacin and diclofenac, have well-described effects to enhance renal water reabsorption and urinary concentrating ability. Concentrating ability is regulated in part at the level of the thick ascending limb of Henle's loop, where active NaCl absorption drives the countercurrent multiplication mechanism. We used semiquantitative immunoblotting to test the effects of indomethacin and diclofenac, given over a 48-h period, on the expression levels of the ion transporters responsible for active NaCl transport in the thick ascending limb. Both agents strongly increased the expression level of the apical Na-K-2Cl cotransporter in both outer medulla and cortex. Neither agent significantly altered outer medullary expression levels of other thick ascending limb proteins, namely, the type 3 Na/H exchanger (NHE-3), Tamm-Horsfall protein, or α1- or β1-subunits of the Na-K-ATPase. Administration of the EP3-selective PGE2analog, misoprostol, to indomethacin-treated rats reversed the stimulatory effect of indomethacin on Na-K-2Cl cotransporter expression. We conclude that cyclooxygenase inhibitors enhance urinary concentrating ability in part through effects to increase Na-K-2Cl cotransporter expression in the thick ascending limb of Henle's loop. This action is most likely due to elimination of an EP3-receptor-mediated tonic inhibitory effect of PGE2 on cAMP production.
Using Information Extraction Rules for Extending Domain Ontologies

In the FRODO project [1] we aim at the development of a “Framework for Distributed Organizational Memories” (OMs). We start with the observation that knowledge and expertise is always heavily distributed in an organization. We accept the fact that this is not an intermediary, imperfect state which should be overcome by a central, ontologically structured information system, but rather a natural and meaningful situation (because during the introduction of OM systems it is normal to start with small, focussed systems which should interoperate later; because much expertise is better to be created, hold, and maintained locally; or because in the case of interorganizational collaborations or virtual teams a deeper integration of information systems cannot be achieved). Hence, a main goal of the FRODO project is to develop a scalable, extensible OM middleware built for easy integration of new components and linking of collaborating components [2]. FRODO builds upon the KnowMore framework for contextually-aware, ontology-based OMs [3,4], but relaxes some constraints of the original model, especially the idea of a centralized OM using one overall set of organizational ontologies. Besides the technical provisions for such a distributed, highly dynamic environment, we lay special emphasis on considerations and methods which are necessary to realize such a scenario in industrial practice. In each industrial environment, besides the questions of smooth introduction of new technology regarding human factors and organizational processes, and besides the question of modeling tools and method support for knowledge (in particular ontologies for structuring OMs or parts of OMs) acquisition, at least two other factors are of utmost importance: One is the predominance of informal, i.e. essentially textbased, representations of knowledge. This is not only just a matter of fact, but really useful, because the cost of formalization is often not in the right relation to the potential benefits such that many informal parts of the scenario are economically reasonable [5]. One implication is that also methods for building formal models must be affordable. The other is the fact that ontologies are not a stand-alone component built once and then remaining untouched, but a living element in the overall scenario, used for different purposes, communicating with other system parts, and representing knowledge about a continuously changing world [10]. These two assumptions lead to two characteristics of our approach:
Regional contributions of Kv1.4, Kv4.2, and Kv4.3 to transient outward K+ current in rat ventricle.

The aim of the present study was to assess differences in transient outward potassium current ( I to) between the right ventricular free wall and the interventricular septum of the adult rat ventricle and to evaluate the relative contributions of Kv4.2, Kv4.3, and Kv1.4 to I to in these regions. The results show that I to is composed of both rapidly and slowly recovering components in the right wall and septum. The fast component had a significantly higher density in the right free wall than in the septum, whereas the slow component did not differ between the two sites. Kv4.2mRNA and protein levels were also highest in the right wall and correlated with I to density, whereas Kv4.3 was expressed uniformly in these regions. The kinetics of the rapidly recovering component of I to in myocytes was similar to that recorded in tsa-201 cells expressing Kv4.2 and Kv4.3 channels. Kv1.4 mRNA and protein expression correlated well with the density of the slowly recovering I to, whereas the recovery kinetics of the slow component were identical to Kv1.4 expressed in tsa-201 cells. In conclusion, expression of Kv1.4, Kv4.2, and Kv4.3 differs between regions in rat hearts. Regionally specific differences in the genetic composition of I to can account for the region-specific properties of this current.
Endogenous glucocorticoids released during acute toxic liver injury enhance hepatic IL-10 synthesis and release.

Endogenous glucocorticoids are known to play a role in the regulation of the inflammatory response possibly by modulating pro- and anti-inflammatory cytokine expression. We examined endogenous glucocorticoid secretion, hepatic damage, tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) mRNA expression and release in rats treated with carbon tetrachloride (CCl4) after treatment with vehicle or a glucocorticoid receptor antagonist (RU-486). Rats treated with CCl4 demonstrated striking elevations of plasma corticosterone levels. Inhibition of endogenous glucocorticoid activity by pretreatment with the glucocorticoid receptor antagonist RU-486 resulted in augmented CCl4-mediated hepatotoxicity, as reflected by histology and serum transaminase levels, which were independent of alterations in serum TNF-α levels or hepatic mRNA expression. CCl4 treatment resulted in enhanced hepatic IL-10 mRNA expression and elevated serum IL-10 levels, which were markedly attenuated by glucocorticoid receptor blockade. In summary, significant endogenous glucocorticoid release occurs during acute toxic liver injury in the rat and suppresses the inflammatory response independent of effects on TNF-α but possibly by upregulating hepatic IL-10 production.
Correlating summarization of multi-source news with k-way graph bi-clustering

With the emergence of enormous amount of online news, it is desirable to construct text mining methods that can extract, compare and highlight similarities of them. In this paper, we explore the research issue and methodology of correlated summarization for a pair of news articles. The algorithm aligns the (sub)topics of the two news articles and summarizes their correlation by sentence extraction. A pair of news articles are modelled with a weighted bipartite graph. A mutual reinforcement principle is applied to identify a dense subgraph of the weighted bipartite graph. Sentences corresponding to the subgraph are correlated well in textual content and convey the dominant shared topic of the pair of news articles. As a further enhancement for lengthy articles, a k-way bi-clustering algorithm can first be used to partition the bipartite graph into several clusters, each containing sentences from the two news reports. These clusters correspond to shared subtopics, and the above mutual reinforcement principle can then be applied to extract topic sentences within each subtopic group.
Cadherin function in junctional complex rearrangement and posttranslational control of cadherin expression.

The role of E-cadherin, a calcium-dependent adhesion protein, in organizing and maintaining epithelial junctions was examined in detail by expressing a fusion protein (GP2-Cad1) composed of the extracellular domain of a nonadherent glycoprotein (GP2) and the transmembrane and cytoplasmic domains of E-cadherin. All studies shown were also replicated using an analogous cell line that expresses a mutant cadherin construct (T151) under the control of tet repressor. Mutant cadherin was expressed at ∼10% of the endogenous E-cadherin level and had no apparent effect on tight junction function or on distributions of adherens junction, tight junction, or desmosomal marker proteins in established Madin-Darby canine kidney cell monolayers. However, GP2-Cad1 accelerated the disassembly of epithelial junctional complexes and delayed their reassembly in calcium switch experiments. Inducing expression of GP2-Cad1 to levels approximately threefold greater than endogenous E-cadherin expression levels in control cells resulted in a decrease in endogenous E-cadherin levels. This was due in part to increased protein turnover, indicating a cellular mechanism for sensing and controlling E-cadherin levels. Cadherin association with catenins is necessary for strong cadherin-mediated cell-cell adhesion. In cells expressing low levels of GP2-Cad1, protein levels and stoichiometry of the endogenous cadherin-catenin complex were unaffected. Thus effects of GP2-Cad1 on epithelial junctional complex assembly and stability were not due to competition with endogenous E-cadherin for catenin binding. Rather, we suggest that GP2-Cad1 interferes with the packing of endogenous cadherin-catenin complexes into higher-order structures in junctional complexes that results in junction destabilization.
Analysis of finite deformation of curved beams bonded with piezoelectric actuating layers

Piezoelectric laminated curved beams or laminated curved smart beams, one of the most popular elements, are widely used in nano- or micro-electromechanical systems due to their excellent properties such as small volume, lightweight, and quick response. In this article, the finite deformation of piezoelectric laminated curved beams is analyzed based on Lagrangian and Eulerian description. The piezoelectric actuating character for the deflection in the curved beams bonded with piezoelectric film (polyvinylidene fluoride) driving layers is investigated. Choosing the deformed radius of curvature and tangent slope angle as fundamental parameters, the governing equations of laminated curved smart beams under static mechanical and electrical loadings are derived. First, the equilibrium equations are deduced and decoupled using the deformed angle of tangent slope as the only variant. And then the analytical solutions of laminated curved smart beams are presented using harmonic functions. Finally, the static deformations of the laminated curved smart beams are calculated by this method and the finite element method. The results exhibit good consistency and show the validation of the present method. Circular and spiral beams covered with piezoelectric layers are researched further. Effects of radius, thickness ratios, and stacking sequence on deflections of the piezoelectric laminated beams are explored as well.
“Appropriate Treatment” and Therapeutic Window in Spasticity Treatment with IncobotulinumtoxinA: From 100 to 1000 Units

Many neurological diseases (ischemic and hemorrhagic stroke, multiple sclerosis, infant cerebral palsy, spinal cord injuries, traumatic brain injury, and other cerebrovascular disorders) may cause muscle spasticity. Different therapeutic strategies have been proposed for the treatment of spasticity. One of the major treatments for tone modulation is botulinum toxin type A (BTX-A), performed in addition to other rehabilitation strategies based on individualized multidisciplinary programs aimed at achieving certain goals for each patient. Therapeutic plans must be precisely defined as they must balance the reduction of spastic hypertonia and retention of residual motor function. To perform and optimize the treatment, an accurate clinical and instrumental evaluation of spasticity is needed to determine how this symptom is invalidating and to choose the best doses, muscles and times of injection in each patient. We introduce an “appropriate treatment” and no “standard or high dosage treatment” concept based on our retrospective observational study on 120 patients lasting two years, according to the larger Therapeutic Index and Therapeutic Window of Incobotulinumtoxin A doses from 100 to 1000 units. We studied the efficiency and safety of this drug considering the clinical spasticity significance for specialist physicians and patients.
Distinct roles for IT and IH in controlling the frequency and timing of rebound spike responses

Non‐Technical Summary The property of excitability is conferred to specific cell types through the action of a host of ion channels. Two classes of ion channels which play crucial roles in cellular excitability are T‐type calcium and hyperpolarization‐activated cyclic‐nucleotide (HCN) channels. Given that T‐type and HCN channel availability is increased upon hyperpolarization, T‐type‐ and HCN‐mediated currents are critical determinants of rebound depolarizations in many cell types. Rebound responses have long been documented in deep cerebellar nuclear (DCN) neurons; however, the extent to which T‐type‐ and HCN‐mediated currents contribute to rebound depolarizations following physiological input has not been established. Using a combination of in vitro electrophysiological and in silico techniques, we define the roles of T‐type‐ and HCN‐mediated currents in controlling the frequency and latency of DCN rebound spike output. Our study demonstrates that T‐type and HCN channels become sufficiently available during physiological levels of hyperpolarization to make distinct contributions to the frequency and latency of rebound responses.
Antisense oligonucleotides against the α-subunit of ENaC decrease lung epithelial cation-channel activity.

Amiloride-sensitive Na+ transport by lung epithelia plays a critical role in maintaining alveolar Na+ and water balance. It has been generally assumed that Na+transport is mediated by the amiloride-sensitive epithelial Na+ channel (ENaC) because molecular biology studies have confirmed the presence of ENaC subunits α, β, and γ in lung epithelia. However, the predominant Na+-transporting channel reported from electrophysiological studies by most laboratories is a nonselective, high-conductance channel that is very different from the highly selective, low-conductance ENaC reported in other tissues. In our laboratory, single-channel recordings from apical membrane patches from rat alveolar type II (ATII) cells in primary culture reveal a nonselective cation channel with a conductance of 20.6 ± 1.1 pS and an Na+-to-K+selectivity of 0.97 ± 0.07. This channel is inhibited by submicromolar concentrations of amiloride. Thus there is some question about the relationship between the gene product observed with single-channel methods and the cloned ENaC subunits. We have employed antisense oligonucleotide methods to block the synthesis of individual ENaC subunit proteins (α, β, and γ) and determined the effect of a reduction in the subunit expression on the density of the nonselective cation channel observed in apical membrane patches on ATII cells. Treatment of ATII cells with antisense oligonucleotides inhibited the production of each subunit protein; however, single-channel recordings showed that only the antisense oligonucleotide targeting the α-subunit resulted in a significant decrease in the density of nonselective cation channels. Inhibition of the β- and γ-subunit proteins alone or together did not cause any changes in the observed channel density. There were no changes in open probability or other channel characteristics. These results support the hypothesis that the α-subunit of ENaC alone or in combination with some protein other than the β- or γ-subunit protein is the major component of lung alveolar epithelial cation channels.
Renal cortical ceramide patterns during ischemic and toxic injury: assessments by HPLC-mass spectrometry.

Ceramides are a class of signaling molecules that can acutely accumulate in tissues as part of a "stress response. " They are classically measured by the diacylglycerol kinase assay, which, in general, measures total ceramide rather than individual moieties within the diverse ceramide family. The present study was undertaken to 1) adapt current HPLC-mass spectrometry technology for measuring individual renal ceramides, and 2) use this technique to more fully characterize the nature of the renal ceramide "stress" reaction. Renal cortical tissues were obtained from CD-1 mice under control conditions and 2 or 18 h after renal injury (ischemia-reperfusion and glycerol-mediated myohemoglobinuria). C24, C22, and C16 ceramides were identified in normal renal cortex, constituting 70, 10, and 20% of the total ceramide pool, respectively. Within each of these families, heterogeneity was apparent because of differing degrees of unsaturation (0-3 double bonds) in the constituent fatty acid of ceramide. Renal injury dramatically changed ceramide profiles: 1) total ceramide increased by ∼300%; 2) although all ceramides participated in this reaction, they did so to differing degrees; 3) this caused pronounced changes in ceramide distribution patterns; 4) injury induced a striking shift toward unsaturated (vs. saturated) fatty acids within the C22 and C24 (but not the C16) ceramide pools; and 5) the extent of these qualitative changes differed according to the etiology of the initiating renal damage. Thus we conclude that ceramide stress response involves major qualitative (and not simply quantitative) changes in ceramide expression that are partially disease dependent. These findings underscore the fact that simply measuring total renal ceramide content (e.g., by diacylglycerol kinase assay) substantially oversimplifies the nature and, hence, the potential implications of the ceramide stress reaction.
Incorporating Genuine Prior Information about Between-Study Heterogeneity in Random Effects Pairwise and Network Meta-analyses

Background. Pairwise and network meta-analyses using fixed effect and random effects models are commonly applied to synthesize evidence from randomized controlled trials. The models differ in their assumptions and the interpretation of the results. The model choice depends on the objective of the analysis and knowledge of the included studies. Fixed effect models are often used because there are too few studies with which to estimate the between-study SD from the data alone. Objectives. The aim of this study was to propose a framework for eliciting an informative prior distribution for the between-study SD in a Bayesian random effects meta-analysis model to genuinely represent heterogeneity when data are sparse. Methods. We developed an elicitation method using external information, such as empirical evidence and expert beliefs, on the “range” of treatment effects to infer the prior distribution for the between-study SD. We also developed the method to be implemented in R. Results. The 3-stage elicitation approach allows uncertainty to be represented by a genuine prior distribution to avoid making misleading inferences. It is flexible to what judgments an expert can provide and is applicable to all types of outcome measures for which a treatment effect can be constructed on an additive scale. Conclusions. The choice between using a fixed effect or random effects meta-analysis model depends on the inferences required and not on the number of available studies. Our elicitation framework captures external evidence about heterogeneity and overcomes the assumption that studies are estimating the same treatment effect, thereby improving the quality of inferences in decision making.
Unloading induces transcriptional activation of the sarco(endo)plasmic reticulum Ca2+-ATPase 1 gene in muscle.

Previous work showed that protein and mRNA levels of the "fast" isoform of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA1) are markedly increased in unloaded slow-twitch soleus muscles, suggesting pretranslational control of gene expression [L. M. Schulte, J. Navarro, and S. C. Kandarian. Am. J. Physiol. 264 ( Cell Physiol. 33): C1308-C1315, 1993]. However, because of the difficulty of measuring transcription rates from whole muscle, transcriptional activation of the SERCA1 gene with unloading has not been confirmed. Because SERCA1 pre-mRNA levels can reflect transcriptional activity, in the present study SERCA1 introns were sequenced to allow intron-directed RT-PCR measurement of SERCA1 pre-mRNA. These data were then compared with changes in SERCA1 mRNA expression in control and unloaded soleus muscles. After 2, 4, and 10 days of unloading, SERCA1 pre-mRNA and mRNA transcript levels increased significantly by two-, three-, and sevenfold, respectively ( P < 0.01). Parallel increases in SERCA1 pre-mRNA and mRNA suggest transcriptional activation of the endogenous SERCA1 gene by muscle unloading. SERCA2, the cardiac/slow-twitch skeletal muscle isoform, was not markedly increased by unloading, and RNase protection assays showed no change in alternative splicing of SERCA1 or SERCA2 primary transcripts. With use of in vivo plasmid injection, the activity of a reporter gene driven by 3.6 kb of the SERCA1 5'-flanking region increased fivefold in 7-day-unloaded soleus muscles. Comparison of the magnitude of transcriptional activation of endogenous and constructed SERCA1 genes by unloading confirms the fidelity of using intronic RT-PCR to examine muscle gene transcription rates and suggests that cis-acting elements sufficient for regulating unloading-induced transcriptional activation are contained in this promoter construct.
Evidence supporting involvement of leukotrienes in LPS-induced hypothermia in mice.

The aim of the present study was to examine a possible involvement of leukotrienes (LTs) in lipopolysaccharide (LPS)-induced body temperature (Tb) response. We examined the effect of MK-886, an inhibitor of LT synthesis, on changes in Tb, plasma tumor necrosis factor-α (TNF-α), hypothalamic LT, and PGE2 production. Intraperitoneal injection of LPS (50 μg/mouse) led to a decrease in Tb starting 1 h after the injection. The hypothermic effect of LPS was accompanied by a significant elevation in TNF-α level in plasma and in LT and PGE2 production by ex vivo-incubated hypothalamus. MK-886 (1 mg/kg ip) administered 4 h before LPS efficaciously prevented LPS-induced hypothermia in mice. Pretreatment of mice with MK-886 did not alter the LPS-stimulated increase in plasma TNF-α. MK-886 significantly inhibited LT and enhanced PGE2 production in hypothalamus compared with LPS alone. These results suggest that 1) LPS-induced hypothermia may be mediated by LTs and 2) the antihypothermic effect of MK-886 is not associated with TNF-α bioactivity.