Miracle-dz/UniFAR-FTUs huggingface dataset:
Preliminary Structure-Activity Relationship on Theonellasterol, a New Chemotype of FXR Antagonist, from the Marine Sponge Theonella swinhoei

Using theonellasterol as a novel FXR antagonist hit, we prepared a series of semi-synthetic derivatives in order to gain insight into the structural requirements for exhibiting antagonistic activity. These derivatives are characterized by modification at the exocyclic carbon-carbon double bond at C-4 and at the hydroxyl group at C-3 and were prepared from theonellasterol using simple reactions. Pharmacological investigation showed that the introduction of a hydroxyl group at C-4 as well as the oxidation at C-3 with or without concomitant modification at the exomethylene functionality preserve the ability of theonellasterol to inhibit FXR transactivation caused by CDCA. Docking analysis showed that the placement of these molecules in the FXR-LBD is well stabilized when on ring A functional groups, able to form hydrogen bonds and π interactions, are present.
Graph Signal Denoising via Trilateral Filter on Graph Spectral Domain

This paper presents a graph signal denoising method with the trilateral filter defined in the graph spectral domain. The original trilateral filter (TF) is a data-dependent filter that is widely used as an edge-preserving smoothing method for image processing. However, because of the data-dependency, one cannot provide its frequency domain representation. To overcome this problem, we establish the graph spectral domain representation of the data-dependent filter, i.e., a spectral graph TF (SGTF). This representation enables us to design an effective graph signal denoising filter with a Tikhonov regularization. Moreover, for the proposed graph denoising filter, we provide a parameter optimization technique to search for a regularization parameter that approximately minimizes the mean squared error w.r. t. the unknown graph signal of interest. Comprehensive experimental results validate our graph signal processing-based approach for images and graph signals.
Eurographics/ Acm Siggraph Symposium on Computer Animation (2007) Weakly Compressible Sph for Free Surface Flows

Permission to make digital or hard copies of part or all of this wor k for per sonal or classr oom use is granted without fee provided that copies are not made or distributed for commer cial advantage and that copies bear this notice and the full citation on the first page. Copyrights for components of this wor k owned by other s than ACM must be honored. Abstracting with cr edit is permitted. To copy other wise, to republish, to post on ser ver s, or to redistribute to lists, requires prior specific permission and/or a fee. Request permissions from Permissions Dept, ACM Abstract We present a weakly compressible form of the Smoothed Particle Hydrodynamics method (SPH) for fluid flow based on the Tait equation. In contrast to commonly employed projection approaches that strictly enforce incompress-ibility, time-consuming solvers for the Poisson equation are avoided by allowing for small, user-defined density fluctuations. We also discuss an improved surface tension model that is particularly appropriate for single-phase free-surface flows. The proposed model is compared to existing models and experiments illustrate the accuracy of the approach for free surface flows. Combining the proposed methods, volume-preserving low-viscosity liquids can be efficiently simulated using SPH. The approach is appropriate for medium-scale and small-scale phenomena. Effects such as splashing and breaking waves are naturally handled.
Influence of the Apolipoprotein E Polymorphism on Plasma Lipoproteins in a Mexican Population

Abstract The influence of apolipoprotein E (APOE) genotypes on plasma lipid levels was determined in 278 Mexican individuals. The most frequent genotype was E3/3 (80.5%) followed by E3/4 (12.5%), E2/3 (5.0%), E2/4 (1.4%), and E4/4 (0.3%). Our data are similar to those previously described for Mexican-American and American Indian populations, which show the highest frequency worldwide of the APOE*3 and the E3/3 genotype. Compared to female carriers of the E3/3 genotype, women with the E3/4 genotype presented increased low-density lipoprotein cholesterol (117 ± 28.0 mg/dL vs. 134.0 ± 31.7 mg/dL, p < 0.05), and total cholesterol (179.4 ± 33.4 mg/dL vs. 197.5 ± 35.4 mg/dL, p < 0.01). Also, we detected increased high-density lipoprotein concentrations in women with the E2/3 genotype (53.7 ± 19.5 mg/dL) when compared to women with the E3/3 genotype (45.2 ± 12.0 mg/dL) (p < 0.032). Our data suggest that genetic variation at the APOE locus in the Mexican population is a genetic factor that influences plasma lipid levels. This effect was observed only in the female population. Additional studies attempting to correlate APOE polymorphism with plasma lipid profile in a large number of individuals would be helpful in establishing the true significance of this polymorphism in the Mexican population.
Impact of left atrial size reduction and endocardial radiofrequency ablation on continuous atrial fibrillation in patients undergoing concomitant cardiac surgery: three-year results.

BACKGROUND AND AIM OF THE STUDY The study aim was to evaluate the efficacy of left atrial (LA) size reduction combined with radiofrequency (RF) ablation in the treatment of continuous atrial fibrillation (AF), by comparative analysis of the outcomes of patients undergoing RF ablation with and without LA size reduction. METHODS A total of 46 patients with continuous AF and cardiac disease underwent cardiac surgery and RF ablation alone (group I, n = 20) or combined with LA size reduction (group II, n = 26). Patients were followed for three years postoperatively, with evaluation of cardiac rhythm, neurological complications, LA size (by echocardiography) and atrial contractility. RESULTS At three years after surgery, sinus rhythm (SR) was restored in 61.1% and 70% of patients in groups I and II, respectively. Mean LA diameter was reduced from 60 +/- 15 mm to 57 +/- 5 mm in group I, and from 69 +/- 19 mm to 55 +/- 6 mm in group II. The overall three-year survival was 90% in group I, and 88.5% in group II. Three-year freedom from stroke was 88.9% and 86.2% in groups I and II, respectively. Two patients in each group received transvenous permanent pacemaker implantation. Atrial contractility was recovered in all patients with stable SR. CONCLUSION LA size reduction improves SR conversion rate after RF ablation for continuous AF in patients undergoing concomitant cardiac surgery.
Intense Synaptic Activity Enhances Temporal Resolution in Spinal Motoneurons

In neurons, spike timing is determined by integration of synaptic potentials in delicate concert with intrinsic properties. Although the integration time is functionally crucial, it remains elusive during network activity. While mechanisms of rapid processing are well documented in sensory systems, agility in motor systems has received little attention. Here we analyze how intense synaptic activity affects integration time in spinal motoneurons during functional motor activity and report a 10-fold decrease. As a result, action potentials can only be predicted from the membrane potential within 10 ms of their occurrence and detected for less than 10 ms after their occurrence. Being shorter than the average inter-spike interval, the AHP has little effect on integration time and spike timing, which instead is entirely determined by fluctuations in membrane potential caused by the barrage of inhibitory and excitatory synaptic activity. By shortening the effective integration time, this intense synaptic input may serve to facilitate the generation of rapid changes in movements.
Cardiac and Metabolic Physiology of Early Larval Zebrafish (Danio rerio) Reflects Parental Swimming Stamina

Swimming stamina in adult fish is heritable, it is unknown if inherited traits that support enhanced swimming stamina in offspring appear only in juveniles and/or adults, or if these traits actually appear earlier in the morphologically quite different larvae. To answer this question, mature adult zebrafish (Danio rerio) were subjected to a swimming performance test that allowed separation into low swimming stamina or high swimming stamina groups. Adults were then bred within their own performance groups. Larval offspring from each of the two groups, designated high (LHSD) and low stamina-derived larvae (LLSD), were then reared at 27°C in aerated water (21% O2). Routine (fH,r) and active (fH,a) heart rate, and routine (Ṁo2,r) and active (Ṁo2,a) mass-specific oxygen consumption were recorded from 5 days post fertilization (dpf) through 21 dpf, and gross cost of transport and factorial aerobic metabolic scope were derived from Ṁo2 measurements. Heart rate generally ranged between 150 and 225 bpm in both LHSD and LLSD populations. However, significant (P < 0.05) differences existed between the LLSD and LHSD populations at 5 and 14 dpf in fH,r and at days 10 and 15 dpf in fH,a. Ṁo2,r was 0.04–0.32 μmol mg−1 h−1, while Ṁo2,a was 0.2–1.2 μmol mg−1 h−1. Significant (P < 0.05) differences between the LLSD and LHSD populations in Ṁo2,r occurred at 7, 10, and 21 dpf and in Ṁo2,a at 7 dpf. Gross cost of transport was ∼6–10 μmol O2·μg−1 m−1 at 5 dpf, peaking at 14–19 μmol O2 μg−1 m−1 at 7–10 dpf, before falling again to 5–6 μmol O2 μg−1 m−1 at 21 dpf, with gross cost of transport significantly higher in the LLSD population at 7 dpf. Collectively, these data indicate that inherited physiological differences known to contribute to enhanced stamina in adult parents also appear in their larval offspring well before attainment of juvenile or adult features.
Developmental Cognitive Neuroscience Neurodevelopmental Correlates of Proneness to Guilt and Shame in Adolescence and Early Adulthood

Keywords: Brain development Cortical thickness MRI Moral emotions Social a b s t r a c t Investigating how brain development during adolescence and early adulthood underlies guilt-and shame-proneness may be important for understanding risk processes for mental disorders. The aim of this study was to investigate the neurodevelopmental correlates of interpersonal guilt-and shame-proneness in healthy adolescents and young adults using structural magnetic resonance imaging (sMRI). Sixty participants (age range: 15–25) completed sMRI and self-report measures of interpersonal guilt-and shame-proneness. Independent of interpersonal guilt, higher levels of shame-proneness were associated with thinner posterior cingulate cortex (PCC) thickness and smaller amygdala volume. Higher levels of shame-proneness were also associated with attenuated age-related reductions in thickness of lateral orbitofrontal cortex (lOFC). Our findings highlight the complexities in understanding brain–behavior relationships during the adolescent/young adult period. Results were consistent with growing evidence that accelerated cortical thinning during adolescence may be associated with superior socioemotional functioning. Further research is required to understand the implications of these findings for mental disorders characterized by higher levels of guilt and shame.
Targeted promoter editing for rice resistance to Xanthomonas oryzae pv. oryzae reveals differential activities for SWEET14‐inducing TAL effectors

Summary As a key virulence strategy to cause bacterial leaf blight, Xanthomonas oryzae pv. oryzae (Xoo) injects into the plant cell DNA‐binding proteins called transcription activator‐like effectors (TALEs) that bind to effector‐binding elements (EBEs) in a sequence‐specific manner, resulting in host gene induction. TALEs AvrXa7, PthXo3, TalC and Tal5, found in geographically distant Xoo strains, all target OsSWEET14, thus considered as a pivotal TALE target acting as major susceptibility factor during rice–Xoo interactions. Here, we report the generation of an allele library of the OsSWEET14 promoter through stable expression of TALE‐nuclease (TALEN) constructs in rice. The susceptibility level of lines carrying mutations in AvrXa7, Tal5 or TalC EBEs was assessed. Plants edited in AvrXa7 or Tal5 EBEs were resistant to bacterial strains relying on the corresponding TALE. Surprisingly, although indels within TalC EBE prevented OsSWEET14 induction in response to BAI3 wild‐type bacteria relying on TalC, loss of TalC responsiveness failed to confer resistance to this strain. The TalC EBE mutant line was, however, resistant to a strain expressing an artificial SWEET14‐inducing TALE whose EBE was also edited in this line. This work offers the first set of alleles edited in TalC EBE and uncovers a distinct, broader range of activities for TalC compared to AvrXa7 or Tal5. We propose the existence of additional targets for TalC beyond SWEET14, suggesting that TALE‐mediated plant susceptibility may result from induction of several, genetically redundant, host susceptibility genes by a single effector.
Comparison of Concept Learning Algorithms

In the context of the Semantic Web, ontologies based on Description Logics are gaining more and more importance for knowledge representation on a large scale. While the need arises for high quality ontologies with large background knowledge to enable powerful machine reasoning, the acquisition of such knowledge is only advancing slowly, because of the lack of appropriate tools. Concept learning algorithms have made a great leap forward and can help to speed up knowledge acquisition in the form of induced concept descriptions. This work investigated whether concept learning algorithms have reached a level on which they can produce result that can be used in an ontology engineering process. Two learning algorithms (YinYang and DL-Learner) are investigated in detail and tested with benchmarks. A method that enables concept learning on large knowledge bases on a SPARQL endpoint is presented and the quality of learned concepts is evaluated in a real use case. A proposal is made to increase the complexity of learned concept descriptions by circumventing the Open World Assumption of Description Logics.
Effects of Micro/Nano Particle Size on Cell Function and Morphology

The cytotoxicity of micro/nano particles in Ti, TiO and carbon nanotube was investigated by in vitro biochemical analyses using human neutrophils. The particles smaller and larger than the neutrophils were used to determine the relationship between cell and pa rticle size with respect to cytotoxicity. As the particle size decreased, the cell survival rate was decreased and, with the good corresponding relation to this, the value of lactate dehydrogenase (LDH ), which is the indication of cell disruption, was increased. The release of superoxide anion showed t he increasing tendency. Proinflammatory cytokines were detected distinctly for 3μm or sm aller particles and very little in more than 10μm, which is closely related to the phagocytosis by neutrophil s. ICP elemental analysis showed that the dissolution from Ti particles was below detection li mit. Micro and nano particles stimulated the cell reactions according to the results of the huma n neutrophil functional tests. As the particle size was smaller, the inflammation was pronounced. The fine particl es less than 3μm caused distinctly the inflammation in the surrounding tissue. All these results i ndicated that the cytotoxicity was induced due to the physical size effect of particles, which is different from the ionic dissolution effect. The clinical phenomenon confirmed the result obtained in vitro ce ll tests. The neutrophils stimulated by fine particles may cause the inflammatory cascade and harm the surrounding tissue.
'Long Term Debt with Hidden Borrowing'

We consider borrowers with the opportunity to raise funds from a competitive banking sector that shares information, and from an alternative hidden lender. The presence of the hidden lender restricts the contracts that can be obtained from the banking sector. In equilibrium some borrowers obtain funds from both the banking sector and the inefficient hidden lender simultaneously. We further show that as the cost of borrowing from the hidden lender increases, total welfare increases. We generalize the model to allow for a partially hidden lender and obtain qualitatively similar results.
Categorical vs Coordinate Relationships do not reduce to spatial frequency differences

Categorical and coordinate stimulus processing were hypothesized by Kosslyn (1987) to be lateralized visual tasks, differentiated by task-relevant spatial frequencies. Slotnick et al. (2001) directly tested Kosslyn’s hypothesis and concluded that the lateralization presents only when tasks are sufficiently difficult. Our differential encoding model is a three layer neural network that accounts for lateralization in visual processing via the biologically plausible mechanism of differences in connection spread of long-range lateral neural connections (Hsiao, Cipollini, & Cottrell, 2013). We show that our model accounts for Slotnick’s data and that Slotnick’s analysis does not convincingly explain their results. Instead, we propose that Kosslyn’s initial hypothesis was based on an incorrect assumption: categorical and coordinate stimuli are not solely differentiated by spatial frequencies. The results that our model captures cannot be reproduced by Ivry and Robertson’s (1998) Double Filtering by Frequency theory, which is driven solely by lateralized spatial frequency processing.
Differential Effects of Teriparatide and Alendronate on Bone Remodeling in Postmenopausal Women Assessed by Histomorphometric Parameters

An 18‐month randomized double‐blind study was conducted in postmenopausal women with osteoporosis to compare the effects of once‐daily teriparatide 20 μg with alendronate 10 mg on bone histomorphometry. Biopsies were obtained from 42 patients. Indices of bone formation were significantly higher after 6 or 18 months of teriparatide compared with alendronate treatment.
Dexamethasone Effect on Postoperative Pain and Tramadol Requirement after Thyroidectomy

Tramadol is a central-acting analgesic associated with nausea and vomiting. Clinical studies have demonstrated that glucocorticoids have analgesic and antiemetic effects when administered perioperatively. The aim of this study is to test the hypothesis that coadministration of tramadol and dexamethasone decreases both postoperative pain and tramadol requirement by patient-controlled analgesia (PCA). Forty female patients undergoing thyroidectomy under general anesthesia were enrolled in a double-blind randomized controlled study and allocated to receive dexamethasone 4 mg i.v. (dexamethasone group, n = 20) or saline (control group, n = 20). At 0, 1, 2, 4 and 22 h of PCA, tramadol consumption and pain were evaluated. Although pain (numerical rating scale 0–10) was significantly lower in the dexamethasone group compared to the control group (2.9 ± 1.4 vs. 3.8 ± 1.2, p = 0.02) at the beginning of PCA, tramadol demand was not significantly different. Although the results herein show a possible beneficial effect of a preoperative single low dose of dexamethasone on postoperative pain, the hypothesis that this corticosteroid decreases tramadol requirement is not supported.
A Novel Partial Agonist of the A1 -Adenosine Receptor and Evidence of Receptor Homogeneity in Adipocytes

This study characterizes the receptor binding and functional effects of CVT-3619 [2-{6-[((1R,2R)-2-hydroxycyclopentyl)-amino]purin-9-yl}(4S,5S,2R,3R)-5-[(2-fluorophenylthio)methyl]-oxolane-3,4-diol], a novel N6-5′ -substituted adenosine analog and A1 -adenosine receptor (A AdoR) agonist, on rat epididymal and inguinal adipocytes and on the isolated heart and compares these effects with those caused by the full agonist N6 -cyclopentyladenosine (CPA). In addition, the hypothesis that adipocyte A1AdoR are a heterogeneous population with regard to their affinities for ligands was tested. CVT-3619 was 10–100-fold selective for A1AdoR versus other AdoR and bound to adipocyte membranes with high (KH = 14 nM) and low (K = 5.4 μM) affinities. CVT-3619 reduced cyclic AMP content and release of nonesterified fatty acids from epididymal adipocytes with IC50 values of 6 and 44 nM, respectively. CVT-3619 was a partial agonist relative to CPA to reduce lipolysis in epididymal and inguinal adipocytes. CVT-3619 did not change atrial rate in rat heart and caused a small (6-ms) prolongation of the stimu-lus-to-His bundle interval without causing atrioventricular block in guinea pig heart (effects mediated by A1AdoR), whereas CPA caused atrioventricular block and near cessation of atrial electrical activity. CVT-3619 increased coronary conductance (effect mediated by A2AAdoR) only at concentrations ≥10 μM. Rat epididymal adipocyte A1AdoR had similar affinities for the antagonist 8-cyclopentyl-1,3-dipropylxanthine in the presence of three dissimilar A AdoR agonists (2-chloro-N6 -cyclopentyladenosine, N6 -sulfophenyladenosine, and N-5′ -ethylcarboxamidoadenosine) as determined by Schild analysis. It was concluded that rat epididymal adipocyte A1AdoR are a homogeneous receptor population with regard to affinities for ligands and that CVT-3619 is a partial agonist with selectivity for A1AdoR and inhibition of lipolysis.
Using Functional Signatures to Identify Repositioned Drugs for Breast, Myelogenous Leukemia and Prostate Cancer

The cost and time to develop a drug continues to be a major barrier to widespread distribution of medication. Although the genomic revolution appears to have had little impact on this problem, and might even have exacerbated it because of the flood of additional and usually ineffective leads, the emergence of high throughput resources promises the possibility of rapid, reliable and systematic identification of approved drugs for originally unintended uses. In this paper we develop and apply a method for identifying such repositioned drug candidates against breast cancer, myelogenous leukemia and prostate cancer by looking for inverse correlations between the most perturbed gene expression levels in human cancer tissue and the most perturbed expression levels induced by bioactive compounds. The method uses variable gene signatures to identify bioactive compounds that modulate a given disease. This is in contrast to previous methods that use small and fixed signatures. This strategy is based on the observation that diseases stem from failed/modified cellular functions, irrespective of the particular genes that contribute to the function, i.e., this strategy targets the functional signatures for a given cancer. This function-based strategy broadens the search space for the effective drugs with an impressive hit rate. Among the 79, 94 and 88 candidate drugs for breast cancer, myelogenous leukemia and prostate cancer, 32%, 13% and 17% respectively are either FDA-approved/in-clinical-trial drugs, or drugs with suggestive literature evidences, with an FDR of 0.01. These findings indicate that the method presented here could lead to a substantial increase in efficiency in drug discovery and development, and has potential application for the personalized medicine.