Miracle-dz/UniFAR-FTUs huggingface dataset:
Acute Hemodynamic Effects of Nebulized Iloprost via the I-Neb Adaptive Aerosol Delivery System in Pulmonary Hypertension

Inhaled iloprost has proven to be an effective therapy in patients with pulmonary hypertension (PH). However, the acute hemodynamic effect of nebulized iloprost delivered via the I-neb Adaptive Aerosol Delivery (AAD) system remains unclear and needs to be assessed. In this study, 126 patients with PH were classified according to current guidelines (59, 34, 29, and 4 patients in groups 1/1′, 3, 4, and 5, respectively; 20 patients had idiopathic pulmonary arterial hypertension [iPAH]), were randomly assigned to inhale iloprost 2.5 μg (n = 67) or 5.0 μg (n = 59) via the I-neb AAD system, and were assessed by right heart catheterization. In seven patients with iPAH, iloprost plasma levels were measured. The two iloprost doses caused decreases from baseline in pulmonary vascular resistance (PVR; 2.5 μg: −14.7%; 5.0 μg: −15.6%) and mean pulmonary arterial pressure (mPAP; 2.5 μg: −11.0%; 5.0 μg: −10.1%) while cardiac index (CI) increased (2.5 μg: +6.5%; 5.0 μg: +6.4%). The subset with iPAH also showed decreases from baseline in PVR and mPAP and an increase in CI. Peak iloprost plasma levels showed no significant difference after inhalation of 2.5 μg or 5.0 μg iloprost (95.5 pg/mL vs. 73.0 pg/mL; P = 0.06). In summary, nebulized iloprost delivered via the I-neb AAD system reduced mPAP and PVR and increased CI from baseline in a heterogeneous group of patients with PH and in the subset with iPAH. In patients with iPAH, inhalation of 2.5 μg or 5.0 μg iloprost resulted in broadly similar peak iloprost plasma levels.
Recessive Antimorphic Alleles Overcome Functionally Redundant Loci to Reveal TSO1 Function in Arabidopsis Flowers and Meristems

Arabidopsis TSO1 encodes a protein with conserved CXC domains known to bind DNA and is homologous to animal proteins that function in chromatin complexes. tso1 mutants fall into two classes due to their distinct phenotypes. Class I, represented by two different missense mutations in the CXC domain, leads to failure in floral organ development, sterility, and fasciated inflorescence meristems. Class II, represented by a nonsense mutation and a T-DNA insertion line, develops wild-type–like flowers and inflorescences but shows severely reduced fertility. The phenotypic variability of tso1 alleles presents challenges in determining the true function of TSO1. In this study, we use artificial microRNA, double mutant analysis, and bimolecular fluorescence complementation assay to investigate the molecular basis underlying these two distinct classes of phenotypes. We show that the class I mutants could be converted into class II by artificial microRNA knockdown of the tso1 mutant transcript, suggesting that class I alleles produce antimorphic mutant proteins that interfere with functionally redundant loci. We identified one such redundant factor coded by the closely related TSO1 homolog SOL2. We show that the class I phenotype can be mimicked by knocking out both TSO1 and its homolog SOL2 in double mutants. Such antimorphic alleles targeting redundant factors are likely prevalent in Arabidopsis and maybe common in organisms with many sets of paralogous genes such as human. Our data challenge the conventional view that recessive alleles are always hypomorphic or null and that antimorphic alleles are always dominant. This study shows that recessive alleles can also be antimorphic and can produce a phenotype more severe than null by interfering with the function of related loci. This finding adds a new paradigm to classical genetic concepts, with important implications for future genetic studies both in basic research as well as in agriculture and medicine.
Geometric displacement on plane and sphere

This paper describes a new algorithm for geometric displacement mapping. Its key idea is that all occluded solutions for an eye ray lie in two-dimensional manifolds perpendicular to the underlying surface to which the height map is applied. The manifold depends only on the eye position and surface geometry, and not on the height field. A simple stepping algorithm, moving along the surface within a manifold renders a curve of pixels to the view plane, which reduces height map rendering to a set of one-dimensional computations that can be done in parallel. The curves on the view plane for two specific underlying manifolds, a plane and a sphere, are straight lines. In this paper we focus on the specific geometry of simple underlying surfaces for which the geometry is more intuitive and the sampling of the rendered image direct.
Transmission of tactile roughness through master-slave systems

In this study, a tactile-roughness transmission system applicable to master-slave systems with a communication time delay is developed. The master-side system constructs a local model of target objects placed in the slave-side environment. Tactile feedbacks presented to an operator at the master side are produced by combining the physical properties of target objects in the local model and the kinetic information of the operator. The time delay between the operator's motion and the tactile feedback is cancelled because the stimuli are synchronized with the exploratory motions. The proposed system is applied to the transmission of tactile-roughness. The tactile stimuli presented to the operator are vibratory stimuli whose amplitude and frequency are controlled. These stimuli are locally synthesized by combining the surface wavelength of target objects and the operator's hand velocity. Using the developed tactile-roughness transmission system, an experiment for transmitting the perceived roughness of grating scales was conducted. As a result, the roughness perceived by the operators was found to highly correlate with the roughness of the scales in the slave-side environment with a coefficient of 0.83.
Mean square analysis of the CLMS and ACLMS for non-circular signals: The approximate uncorrelating transform approach

Current approaches to the mean-square analyses of the complex-least-mean-square (CLMS) and augmented CLMS (ACLMS) algorithms can be challenging due to the difficulty in diagonalising the augmented covariance matrix. By employing the recently introduced approximate uncorrelating transform (AUT), which diagonalizes the covariance and pseudocovariance matrices with a single singular value decomposition (SVD), we derive closed form expressions for both transient and steady-state mean square stability for the CLMS and ACLMS. Relationships between the degree of circularity of the input signal and the bound on the step-sizes of the CLMS and ACLMS are also established. We also show that for both CLMS and ACLMS, the steady-state misadjustment increases with the degree of non-circularity of the input signal. Simulations in the context of frequency estimation in power grid support the analyses.
An in vitro assessment of gas trapping during high frequency oscillation

Our aim was to assess the influence of oscillatory frequency, inspiratory-to-expiratory (I:E) ratio and airway pressure on gas trapping during high frequency oscillatory ventilation (HFOV). A lung model was used, which had a high compliance (4.0 ml (cmH2O)−1) and resistance (160 cmH2O l−1 s−1) resulting in a long time constant (0.64 s). To assess whether gas trapping occurred, the mean pressure within the lung model (equivalent to alveolar pressure) was compared to the mean airway pressure (MAP) measured at the manifold (manifold MAP) of the two oscillators used, the SLE 5000 (I:E ratio 1:1) and the Sensor Medics 3100A (tested at I:E ratios of 1:2 and 1:1). The effects were assessed of raising the MAP from 15 to 35 cmH2O, the oscillatory amplitude from 30 to 70 cmH2O and the frequency from 5 to 15 Hz (5 to 20 Hz SLE only). There were no significant trends for differences between the pressure within the lung model and the ‘manifold’ MAP to increase (i.e. no evidence of gas trapping), as MAP, amplitude or frequency was increased, regardless of which oscillator or I:E ratio was used. Increasing the pressure amplitude led to a progressive fall in the pressure within the lung model when an I:E ratio of 1:2 was used (p < 0.05). Our results suggest that significant gas trapping does not occur during HFOV even if there is high compliance and resistance.
Predicting Bugs in Software Code Changes Using Isolation Forest

Identifying bug immediately when it is introduced can help improve the validity and effectiveness of bug fixing. Predicting bugs in software code changes makes such identification possible. Buggy changes, changes that introduce bugs into source code, can be viewed as anomalies relative to clean changes for that they are rare and irregular. Thus, anomaly detection techniques can be applied to buggy change prediction. Isolation Forest, which detects anomalies based on the hypothesis that the anomalies have the shortest average path length on the constructed random forest, has exhibited its good performance on anomaly detection compared to other anomaly detection methods. In this paper, we adopt it in predicting bugs in software code changes. Empirical study with eight practical open source projects are conducted to validate the effective of Isolation Forest in bug prediction in software code changes. Results of the empirical study show that compared to traditional classification methods used in literature, Isolation Forest can achieve better clean precision, buggy recall, buggy F-measure, AUC and Gmean.
Vitamin A status does not influence neopterin production during illness or health in South African children

Excessive interferon-gamma (IFN-γ) production appears to be a primary immunological lesion in vitamin A-deficient experimental animals but comparable data from humans is lacking. We investigated IFN-γ production in South African children by measurement of urinary excretion of neopterin, a product of IFN-γ-activated monocytes or macrophages. Preschool children were examined during an acute inflammatory illness resulting from accidental ingestion of kerosene and they and a neighbourhood control child were examined 3 months later when well. Vitamin A status was assessed by the modified relative dose response (MRDR) test at 3 months and serum retinol and acute phase proteins were measured at both time points. Urinary neopterin was measured for forty cases in hospital, forty-six cases after recovery, and forty-one controls. Significantly increased neopterin excretion was seen following kerosene ingestion and in association with raised serum acute phase protein concentrations. There was no relationship between neopterin excretion at either time point and vitamin A status as assessed by MRDR test. Urinary neopterin was negatively correlated with serum retinol but no significant relationship was observed when acute phase protein concentrations were included in a multiple regression, suggesting the correlation was secondary to illness-induced changes in serum retinol. The results indicate that, contrary to what is observed in rodents under experimental conditions, poor vitamin A status is not associated with altered regulation of IFN-γ production in children.
Antiproliferative Effects and Mechanism of Action of SCH 56592 against Trypanosoma (Schizotrypanum)cruzi: In Vitro and In Vivo Studies

ABSTRACT We have investigated the antiproliferative effects of SCH 56592, a new experimental triazole, against Trypanosoma(Schizotrypanum) cruzi, the etiological agent of Chagas’ disease in Latin America. SCH 56592 blocked the proliferation of the epimastigote form of the parasite in vitro at 30 nM, a concentration 30- to 100-fold lower than that required with the reference compounds ketoconazole and itraconazole. At that concentration all the parasite’s endogenous sterols (ergosterol, 24-ethyl-cholesta-5,7,22-trien-3β-ol, and its 22-dihydro analogs), were replaced by methylated sterols (lanosterol and 24-methylene-dihydrolanosterol), as revealed by high-resolution gas chromatography coupled with mass spectrometry. This indicated that the primary mechanism of action of the drug was inhibition of the parasite’s sterol C-14α demethylase. Against the clinically relevant intracellular amastigote form, grown in cultured Vero cells at 37°C, the MIC of SCH 56592 was 0.3 nM, again 33- to 100-fold lower than that of ketoconazole or itraconazole. In a murine model of acute Chagas’ disease, SCH 56592 given at ≥ 10 mg/kg of body weight/day for a total of 43 doses allowed 85 to 100% survival and 90 to 100% cure of the surviving animals, as verified by parasitological, serological, and PCR-based tests, while ketoconazole given at 30 mg/kg day allowed 60% survival but only 20% cure. In a murine model of chronic Chagas’ disease, SCH 56592 was again more effective than ketoconazole, providing 75 to 85% protection from death, with 60 to 75% parasitological cures of the surviving animals, while no parasitological cures were observed with ketoconazole. The results indicate that SCH 56592 is the most powerful sterol biosynthesis inhibitor ever tested against T. cruzi and may be useful in the treatment of human Chagas’ disease.
Response of fish tissue mercury in a freshwater lake to local, regional, and global changes in mercury emissions

A suite of mechanistic atmospheric and mercury (Hg) cycling and bioaccumulation models is applied to simulate atmospheric Hg deposition and Hg concentrations in the water column and in fish in a Hg‐impaired freshwater lake located in the northeastern United States that receives its Hg loading primarily through deposition. Two future‐year scenarios evaluate the long‐term response of fish tissue Hg concentrations to reductions in local and nationwide coal‐fired electric‐generating utility and other Hg emissions and an increase or decrease in global (non‐US) Hg emissions. Results indicate that fish tissue Hg concentrations in this ecosystem could require approximately 3 yr to 8 yr to begin to respond to declines in US emissions and deposition with a fish Hg reduction proportional to deposition reduction requiring over 50 yr. Furthermore, recovery could potentially be partially or completely offset by growth in non‐US Hg emissions. Environ Toxicol Chem 2014;33:1238–1247. © 2014 SETAC
Adaptive Gaussian Mixture Model for Skin Color Segmentation

to adapt itself with the environmental changes. The spatial and temporal constraints are also applied to the model adaptation which makes the method applicable to motion detection in video stream compression as well. These considerations put our algorithm in both pixel-based and region based groups of methods. The remainder of this paper is organized as follows. Section II describes the different color space conversions that are used in the skin color modeling. Section III discusses the Gaussian mixture model followed by Section IV describes the modified Expectation maximization algorithm. Section V explains model adaptation. Experimental results are discussed in Section VI. Finally, conclusions are given in Section VII. II. SKIN COLOR MODELING Pixel-based skin color detection methods aim at introducing a tool for measuring the distance of each pixel color to skin color tones. The color itself can be represented in many different ways among which the most widely used ones are summarized below.
Movement Velocity as a Measure of Loading Intensity in Resistance Training

This study examined the possibility of using movement velocity as an indicator of relative load in the bench press (BP) exercise. One hundred and twenty strength-trained males performed a test (T1) with increasing loads for the individual determination of the one-repetition maximum (1RM) and full load-velocity profile. Fifty-six subjects performed the test on a second occasion (T2) following 6 weeks of training. A very close relationship between mean propulsive velocity (MPV) and load (%1RM) was observed (R (2)=0.98). Mean velocity attained with 1RM was 0.16+/-0.04 m x s(-1) and was found to influence the MPV attained with each %1RM. Despite a mean increase of 9.3% in 1RM from T1 to T2, MPV for each %1RM remained stable. Stability in the load-velocity relationship was also confirmed regardless of individual relative strength. These results confirm an inextricable relationship between relative load and MPV in the BP that makes it possible to: 1) evaluate maximal strength without the need to perform a 1RM test, or test of maximum number of repetitions to failure (XRM); 2) determine the %1RM that is being used as soon as the first repetition with any given load is performed; 3) prescribe and monitor training load according to velocity, instead of percentages of 1RM or XRM.
Exploring Mate Value across Two Studies: From Perceptions to Enhancement

Study 1 followed a dual perceptive approach and compared romantic partners’ mate value and mate value discrepancy to determine who the “better half” was in relationships. Results indicated both partners are the “better half” in relationships. Males and females perceived their partners to have higher mate values than themselves in more established relationships. Results also revealed a ceiling effect for commitment in engaged/married relationships, in that commitment no longer influenced perceptions of partner mate value in stabilized relationships. Thus, Study 2 explored perceptions of communication satisfaction and nonverbal immediacy and their influence on perceptions of partner mate value. Results found only communication satisfaction predicted how individuals viewed their partners’ mate value.
GTP activator and dNTP substrates of HIV-1 restriction factor SAMHD1 generate a long-lived activated state

Significance The degradative dNTP triphosphohydrolase activity of the sterile α-motif/histidine-aspartate domain-containing protein 1 (SAMHD1) enzyme helps maintain optimal dNTP balances for DNA replication and also serves as an HIV-1 restriction factor in resting CD4+ target cells of HIV by depleting dNTP substrates of reverse transcriptase. This study shows that full activation of SAMHD1 involves ordered binding of GTP and substrate dNTPs to activator and substrate sites on the enzyme, leading to ordered assembly of the tetramer active form. After the enzyme is activated, it no longer communicates with free activator nucleotides, which contributes to efficient depletion of dNTP pools in resting T cells. The HIV-1 restriction factor sterile α-motif/histidine-aspartate domain-containing protein 1 (SAMHD1) is a tetrameric protein that catalyzes the hydrolysis of all dNTPs to the deoxynucleoside and tripolyphosphate, which effectively depletes the dNTP substrates of HIV reverse transcriptase. Here, we establish that SAMHD1 is activated by GTP binding to guanine-specific activator sites (A1) as well as coactivation by substrate dNTP binding to a distinct set of nonspecific activator sites (A2). Combined activation by GTP and dNTPs results in a long-lived tetrameric form of SAMHD1 that persists for hours, even after activating nucleotides are withdrawn from the solution. These results reveal an ordered model for assembly of SAMHD1 tetramer from its inactive monomer and dimer forms, where GTP binding to the A1 sites generates dimer and dNTP binding to the A2 and catalytic sites generates active tetramer. Thus, cellular regulation of active SAMHD1 is not determined by GTP alone but instead, the levels of all dNTPs and the generation of a persistent tetramer that is not in equilibrium with free activators. The significance of the long-lived activated state is that SAMHD1 can remain active long after dNTP pools have been reduced to a level that would lead to inactivation. This property would be important in resting CD4+ T cells, where dNTP pools are reduced to nanomolar levels to restrict infection by HIV-1.
A review of tactical planning models

The aim of this paper is to give an overview on models and methods used to solve tactical planning problems. The modeling and the elaboration of the well-know tactical planning problems (master planning & scheduling, material requirement planning and multi-site planning) are discussed. These problems are modeled from two “lot sizing” models called the Capacitated Lot Sizing Problem (CLSP) and Multi Level Capacitated Lot Sizing Problem (MLCLSP). From both models, a lot of extensions has been proposed in the literature. The purpose of this paper is twofold: first, classifications of the CLSP and MLCLSP as well as their extensions are given. For each model, the major scientific contributions are mentioned. These classifications made from seventy papers give an overview of “lot sizing” models dedicated to the MPS, MRP and Multi-site and show the diversity of models. Second, from a classification, an analysis of methods used for each model is given. The instance size, best gap and reference for gap computation are given for each contribution. This work can be used to elaborate an optimization tool for tactical planning problematic such as Advanced Planning System.
Dual Targeting of the Cyclin/Rb/E2F and Mitochondrial Pathways in Mantle Cell Lymphoma with the Translation Inhibitor Silvestrol

Purpose: During cell-cycle progression, D-cyclins activate cyclin-dependent kinases (CDKs) 4/6 to inactivate Rb, permitting E2F1-mediated S-phase gene transcription. This critical pathway is typically deregulated in cancer, and novel inhibitory strategies would be effective in a variety of tumors. The protein synthesis inhibitor silvestrol has potent activity in B-cell leukemias via the mitochondrial pathway of apoptosis, and also reduces cyclin D1 expression in breast cancer and lymphoma cell lines. We hypothesized that this dual activity of silvestrol would make it especially effective in malignancies driven by aberrant cyclin D1 expression. Experimental Design: Mantle cell lymphoma (MCL), characterized by elevated cyclin D1, was used as a model to test this approach. The cyclin D/Rb/E2F1 pathway was investigated in vitro using MCL cell lines and primary tumor cells. Silvestrol was also evaluated in vivo using an aggressive model of MCL. Results: Silvestrol showed low nanomolar potency both in MCL cell lines and primary MCL tumor cells. D-cyclins were depleted with just 10 nmol/L silvestrol at 16 hours, with subsequent reductions of phosphorylated Rb, E2F1 protein, and E2F1 target transcription. As showed in other leukemias, silvestrol caused Mcl-1 depletion followed by mitochondrial depolarization and caspase-dependent apoptosis, effects not related to inhibition of CDK4/6. Silvestrol significantly (P < 0.0001) prolonged survival in a MCL xenograft model without detectable toxicity. Conclusions: These data indicate that silvestrol effectively targets the cyclin/CDK/Rb pathway, and additionally induces cytotoxicity via intrinsic apoptosis. This dual activity may be an effective therapeutic strategy in MCL and other malignancies. Clin Cancer Res; 18(17); 4600–11. ©2012 AACR.