Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetic Model Selection for Target Controlled Infusions of Propofol: Assessment of Three Parameter Sets

Background Computer-assisted target controlled infusions (TCI) result in prediction errors that are influenced by pharmacokinetic variability among and within patients. it is uncertain whether the selection of a propofol pharmacokinetic parameter set significantly influences drug concentrations and clinical acceptability. Methods Thirty patients received similar propofol TCI regimens after being randomly allocated to one of three parameter sets. Arterial and venous concentrations were measured and prediction errors calculated from pooled and intrasubject data. Results Arterial propofol concentrations in the Dyck group revealed greater bias (mean 43%) than did those in the Marsh (-1%) and Tackley (-3%) groups. The Dyck group also showed greater inaccuracy (mean:47%) than the Marsh (29%) and Tackley (24%) groups. There was little tendency for measured concentrations to vary from targeted values over time (divergence). Variability about an observed mean in individual patients (wobble) was low. Venous propofol concentrations were initially much less than arterial concentrations, but this difference decreased over time. Conclusions Although it may be preferable to administer propofol TCI by using a locally derived parameter set, it is acceptable to use a model from elsewhere. The Marsh and Tackley models produced equally good performance and are appropriate for propofol TCI within the range of 3-6 micro gram/ml. The Dyck model was less accurate at maintaining anesthetic concentrations, possibly because it was derived from low concentrations. Concentrations in blood, the most sensitive indicators of performance, demonstrated differences among the parameter sets. Clinically, TCI worked well, and by clinical criteria, the choice of pharmacokinetic model did not appear to make a difference.
Brain Volume and Diffusion Markers as Predictors of Disability and Short-Term Disease Evolution in Multiple Sclerosis

BACKGROUND AND PURPOSE: MRI markers of neuroaxonal damage in MS have emerged as critical long-term predictors of MS-related disability. Here we investigated the potential of whole-brain diffusivity and brain volume for the prediction of cross-sectional disability and short- to medium-term clinical evolution. MATERIALS AND METHODS: In this multimodal prospective longitudinal MRI study of 54 patients with MS (87% under immunomodulatory therapy, baseline and follow-up at a median of 12 months), ADC histogram analysis, WM lesion load, BPF, whole-brain atrophy rate, MSFC score, and EDSS score were obtained. A total of 44 patients with no relapse at both time points were included. RESULTS: At both time points, ADC histogram analysis provided robust predictors of the MSFC scores (maximal R2 = 0.576, P < .001), incorporated cognition and fine-motor skill subscores, and EDSS scores. Significant changes beyond physiologic age-related changes at follow-up were noted for ADC histogram markers and BPF. Stronger diffusivity alterations and brain volume at baseline predicted MSFC decline, as demonstrated by multiple linear regression analysis (mean ADC, R2 = 0.203; P = .003) and lower baseline BPF in patients with declined compared with stable MSFC scores (P = .001). Results were independent of intercurrent relapses. CONCLUSIONS: Diffusion histogram analysis provided stable surrogates of disability in MS and proved sensitive for monitoring disease progression during a median of 12 months. Advanced neuroaxonal pathology at baseline was indicative of an increased risk for sustained progression during a median of 12 months, independent of intercurrent relapses.
Dissociation of GLUT4 Translocation and Insulin-stimulated Glucose Transport in Transgenic Mice Overexpressing GLUT1 in Skeletal Muscle*

Overexpression of the human GLUT1 glucose transporter protein in skeletal muscle of transgenic mice results in large increases in basal glucose transport and metabolism, but impaired stimulation of glucose transport by insulin, contractions, or hypoxia (Gulve, E. A., Ren, J.-M., Marshall, B. A., Gao, J., Hansen, P. A., Holloszy, J. O., and Mueckler, M. (1994)J. Biol. Chem. 269, 18366–18370). This study examined the relationship between glucose transport and cell-surface glucose transporter content in isolated skeletal muscle from wild-type and GLUT1-overexpressing mice using 2-deoxyglucose, 3-O-methylglucose, and the 2-N-[4-(1-azi-2,2,2-trifluoroethyl)benzoyl]-1,3-bis(d-mannos-4-yloxy)-2-propylamine exofacial photolabeling technique. Insulin (2 milliunits/ml) stimulated a 3-fold increase in 2-deoxyglucose uptake in extensor digitorum longus muscles of control mice (0.47 ± 0.07 μmol/ml/20 min in basal muscle versus 1.44 μmol/ml/20 min in insulin-stimulated muscle; mean ± S.E.). Insulin failed to increase 2-deoxyglucose uptake above basal rates in muscles overexpressing GLUT1 (4.00 ± 0.40 μmol/ml/20 min in basal muscle versus 3.96 ± 0.37 μmol/ml/20 min in insulin-stimulated muscle). A similar lack of insulin stimulation in muscles overexpressing GLUT1 was observed using 3-O-methylglucose. However, the magnitude of the insulin-stimulated increase in cell-surface GLUT4 photolabeling was nearly identical (∼3-fold) in wild-type and GLUT1-overexpressing muscles. This apparently normal insulin-stimulated translocation of GLUT4 in GLUT1-overexpressing muscle was confirmed by immunoelectron microscopy. Our findings suggest that GLUT4 activity at the plasma membrane can be dissociated from the plasma membrane content of GLUT4 molecules and thus suggest that the intrinsic activity of GLUT4 is subject to regulation.
Stromal Cell‐Derived Factor‐1 Mediates Cardiac Allograft Tolerance Induced by Human Endometrial Regenerative Cell‐Based Therapy

Endometrial regenerative cells (ERCs) are mesenchymal‐like stromal cells, and their therapeutic potential has been tested in the prevention of renal ischemic reperfusion injury, acute liver injury, ulcerative colitis, and immunosuppression. However, their potential in the induction of transplant tolerance has not been investigated. The present study was undertaken to investigate the efficacy of ERCs in inducing cardiac allograft tolerance and the function of stromal cell‐derived factor‐1 (SDF‐1) in the ERC‐mediated immunoregulation. The inhibitory efficacy of human ERCs in the presence or absence of rapamycin was examined in both mouse cardiac allograft models between BALB/c (H‐2d) donors and C57BL/6 (H‐2b) recipients and in vitro cocultured splenocytes. AMD3100 was used to inhibit the function of SDF‐1. Intragraft antibody (IgG and IgM) deposition and immune cell (CD4+ and CD8+) infiltration were measured by immunohistochemical staining, and splenocyte phenotypes were determined by fluorescence‐activated cell sorting analysis. The results showed that ERC‐based therapy induced donor‐specific allograft tolerance, and functionally inhibiting SDF‐1 resulted in severe allograft rejection. The negative effects of inhibiting SDF‐1 on allograft survival were correlated with increased levels of intragraft antibodies and infiltrating immune cells, and also with reduced levels of regulatory immune cells including MHC class IIlowCD86lowCD40lowdendritic cells, CD68+CD206+macrophages, CD4+CD25+Foxp3+T cells, and CD1dhighCD5highCD83lowIL‐10highB cells both in vivo and in vitro. These data showed that human ERC‐based therapy induces cardiac allograft tolerance in mice, which is associated with SDF‐1 activity, suggesting that SDF‐1 mediates the immunosuppression of ERC‐based therapy for the induction of transplant tolerance. Stem Cells Translational Medicine 2017;6:1997–2008
Post-Stroke Lower Limb Spasticity Alters the Interlimb Temporal Synchronization of Centre of Pressure Displacements Across Multiple Timescales

Lower limb spasticity is a common sensorimotor consequence post-stroke, which further complicates stability control by altering the temporal relationship between individual-limb centre of pressure (COP) displacements. The present work employed the discrete wavelet transform to better understand the influence of lower limb spasticity on the control of standing balance, which occurs across multiple timescales. An 8-level decomposition of the individual-limb COP was performed, using retrospective data from 91 stroke survivors with (n = 29) and without (n = 56) lower limb spasticity. Inter-limb temporal synchrony and spatial symmetry at each timescale were evaluated by the cross correlation coefficient at zero phase-lag and the root mean square ratio, respectively, using the reconstructed time series at each timescale. Reduced temporal synchrony was observed among individuals with lower limb spasticity at frequencies down to 0.20 Hz. The present results suggest that the additional balance control challenges associated with post-stroke lower limb spasticity may be linked to the ability to temporally co-modulate the more rapid COP displacements. This may be particularly problematic if individuals are faced with balance perturbations, which require rapid reactive balance corrections to regain stability.
How to have narrow-stripe semiconductor lasers self-pulsate

The rate equations of narrow-stripe semiconductor lasers are considered. These equations represent the dynamics of the photon number and the electron densities in the active and absorbing regions. Having the rate equations, (i) it is shown that the laser is the bounded-input bounded-state (BIBS) and the bounded-input bounded-output (BIBO) stable; (ii) the amplitudes of step inputs are determined for which all equilibrium points of the laser are unstable. The boundedness of the laser output and the instability of its equilibrium points imply that the laser can have a periodic, a quasi-periodic, or a chaotic output. When the output is periodic, the laser is self-pulsating, which is the desirable behavior of the laser. Moreover, a procedure is given to determine the values of laser parameters for which the laser self-pulsates.
Heregulin Induces Transcriptional Activation of the Progesterone Receptor by a Mechanism That Requires Functional ErbB-2 and Mitogen-Activated Protein Kinase Activation in Breast Cancer Cells

ABSTRACT The present study addresses the capacity of heregulin (HRG), a ligand of type I receptor tyrosine kinases, to transactivate the progesterone receptor (PR). For this purpose, we studied, on the one hand, an experimental model of hormonal carcinogenesis in which the synthetic progestin medroxyprogesterone acetate (MPA) induced mammary adenocarcinomas in female BALB/c mice and, on the other hand, the human breast cancer cell line T47D. HRG was able to exquisitely regulate biochemical attributes of PR in a way that mimicked PR activation by progestins. Thus, HRG treatment of primary cultures of epithelial cells of the progestin-dependent C4HD murine mammary tumor line and of T47D cells induced a decrease of protein levels of PRA and -B isoforms and the downregulation of progesterone-binding sites. HRG also promoted a significant increase in the percentage of PR localized in the nucleus in both cell types. DNA mobility shift assay revealed that HRG was able to induce PR binding to a progesterone response element (PRE) in C4HD and T47D cells. Transient transfections of C4HD and T47D cells with a plasmid containing a PRE upstream of a chloramphenicol acetyltransferase (CAT) gene demonstrated that HRG promoted a significant increase in CAT activity. In order to assess the molecular mechanisms underlying PR transactivation by HRG, we blocked ErbB-2 expression in C4HD and T47D cells by using antisense oligodeoxynucleotides to ErbB-2 mRNA, which resulted in the abolishment of HRG's capacity to induce PR binding to a PRE, as well as CAT activity in the transient-transfection assays. Although the inhibition of HRG binding to ErbB-3 by an anti-ErbB-3 monoclonal antibody suppressed HRG-induced PR activation, the abolishment of HRG binding to ErbB-4 had no effect on HRG activation of PR. To investigate the role of mitogen-activated protein kinases (MAPKs), we used the selective MEK1/MAPK inhibitor PD98059. Blockage of MAPK activation resulted in complete abrogation of HRG's capacity to induce PR binding to a PRE, as well as CAT activity. Finally, we demonstrate here for the first time that HRG-activated MAPK can phosphorylate both human and mouse PR in vitro.
On the development of a C-band active array front-end for an airborne polarimetric radar

MIT Lincoln Laboratory (MIT LL), in an effort sponsored by the National Center of Atmospheric Research (NCAR), has engaged in the development of C-Band active element phased array front-end hardware for a polarimetric radar application. This polarimetric active element scanning array (AESA) radar, when fully developed, would be deployed on a C-130 for use in Hurricane Hunter-like missions. The combination of mission and platform imposes requirements on the RF hardware that are often in conflict. These specifications include minimum range and resolution, maximum prime power, and a challenging cross-polarization isolation requirement. The RF hardware developed included a dual polarization (pol) radiator test panel, an alternating transmit simultaneous receive (ATSR) transmit/receive (T/R) switch designed and manufactured by M/A-COM Technical Solutions (MTS), a three channel T/R multichip module (MCM), and a four-pack T/R module assembly. This paper describes the mission and platform requirements, presents a notional design for the phased array aperture, discusses the design trades, and provides an overview of the design and performance of the radiator test panel, the MCM and the four-pack T/R module. This work borrowed heavily in terms of materials, technologies, and lessons learned acquired over the past five years from the MPAR Panel [1] development efforts of MIT LL and MTS co-sponsored by the Federal Aviation Administration (FAA), the Air Force, and the National Severe Storms Laboratory.
Application of a mild traumatic brain injury rehabilitation program in a virtual realty environment: a case study.

BACKGROUND AND PURPOSE Mild traumatic brain injury (mTBI) can compromise reaction time, visual perception, memory, attention, balance, and gait. These deficits, especially if persistent, can restrict participation in daily activities and the resumption of personal and profession roles. The purpose of this case study is to describe an mTBI-specific clinical assessment and rehabilitation intervention administered in a virtual reality environment. CASE DESCRIPTION The case involved a 31-year-old male service member who had sustained an mTBI (concussion) during a recreational softball game 36 days prior to physical therapist evaluation. He had complaints of severe visual and physical motion intolerance. He demonstrated impaired static balance and was restricted from full military duty. INTERVENTIONS The assessment included measurements of postural and gait balance during cognitive, visual, and vestibular challenges within a Computer-Assisted Rehabilitation Environment. Phase 1 of the intervention consisted of clinical techniques (ie, optokinetic stimulation/habituation, visual/physical perturbations, and postural stability exercises) targeting specific impairments. Phase 2 training consisted of weapon handling and target recognition tasks to simulate the requirements of his military occupation. OUTCOMES At the conclusion of 6 treatments, the patient demonstrated significant increases in postural and gait balance with a near complete resolution of all postconcussion symptoms. He successfully returned to full duty and training for combat deployment. DISCUSSION Service members and civilians exhibit similar impairments, limitations, and restrictions following mTBI. A rehabilitation program delivered in a virtual-reality environment can be structured to manage complex mTBI symptoms through the integration of multiple treatment modalities specific to a patient's personal and professional roles.
Impaired Uptake and/or Utilization of Leucine by Saccharomyces cerevisiae Is Suppressed by the SPT15-300 Allele of the TATA-Binding Protein Gene

ABSTRACT Successful fermentations to produce ethanol require microbial strains that have a high tolerance to glucose and ethanol. Enhanced glucose/ethanol tolerance of the laboratory yeast Saccharomyces cerevisiae strain BY4741 under certain growth conditions as a consequence of the expression of a dominant mutant allele of the SPT15 gene (SPT15-300) corresponding to the three amino acid changes F177S, Y195H, and K218R has been reported (H. Alper, J. Moxley, E. Nevoigt, G. R. Fink, and G. Stephanopoulos, Science 314:1565-1568, 2006). The SPT15 gene codes for the TATA-binding protein. This finding prompted us to examine the effect of expression of the SPT15-300 allele in various yeast species of industrial importance. Expression of SPT15-300 in leucine-prototrophic strains of S. cerevisiae, Saccharomyces bayanus, or Saccharomyces pastorianus (lager brewing yeast), however, did not improve tolerance to ethanol on complex rich medium (yeast extract-peptone-dextrose). The enhanced growth of the laboratory yeast strain BY4741 expressing the SPT15-300 mutant allele was seen only on defined media with low concentrations of leucine, indicating that the apparent improved growth in the presence of ethanol was indeed associated with enhanced uptake and/or utilization of leucine. Reexamination of the microarray data published by Alper and coworkers likewise suggested that expression of genes coding for the leucine permeases, Tat1p and Bap3p, were upregulated in the SPT15-300 mutant, as was expression of the genes ARO10, ADH3, ADH5, and SFA1, involved in leucine degradation.
Review of "Linear Models, by S. R. Searle"

A sleeve is formed from sheet material, such as paperboard or the like, which sleeve is adapted to be wrapped about a tub having a tapered side wall. The sleeve is formed with two pairs of opposed side walls. One pair of the opposed side walls has the same taper as the wall of the tub and the other pair of opposed side walls is perpendicular to the top and bottom panels of the sleeve. The tub engages tuck flaps on the sleeve to hold the sleeve in place on the tub. The sleeved tubs can be stacked on their tops, bottoms, or on the perpendicular side walls.
Making Sense of Nonsense

When are people sensitive to the magnitude of numerical information presented in unfamiliar units, such as a price in a foreign currency or a measurement of an unfamiliar product attribute? We propose that people exhibit deliberational blindness, a failure to consider the meaning of even unfamiliar units. When an unfamiliar unit is not salient, people fail to take their lack of knowledge into account, and their judgments reflect sensitivity to the magnitude of the number. However, subtly manipulating the visual salience of the unit (e.g., enlarging its font size relative to the font size of the number) prompts recognition of the unit’s unfamiliarity and reduces magnitude sensitivity. In five experiments, we demonstrated this unit-salience effect, provided evidence for deliberational blindness, and ruled out alternative explanations, such as nonperception and fluency. These findings have implications for decision making involving numerical information expressed in both unfamiliar units and familiar but poorly calibrated units.
Effect of methylphenidate on fatigue in women with recurrent gynecologic cancer

Objective: Fatigue is the most common and often the most bothersome complaint of individuals who are treated for cancer. One intervention now commonly suggested to treat fatigue is the use of psychostimulant medication. Early studies indicate some success in individuals with a mixed cancer diagnoses. This study evaluates the effect of methylphenidate on fatigue in women with recurrent gynecologic cancer.
Application of microcomputed tomography for quantitative analysis of dental root canal obturations.

INTRODUCTION The aim of the study was to apply microcomputed tomography to quantitative evaluation of voids and to test any specific location of voids in tooth's root canal obturations. MATERIALS AND METHODS Twenty root canals were prepared and obturated with gutta-percha and Tubli-Seal sealer using the thermoplastic compaction method (System B+Obtura II). Roots were scanned and three-dimensional visualization was obtained. The volume and Feret's diameter of I-voids (at the filling/dentine interface) and S-voids (surrounded by filling material) were measured. RESULTS The results revealed that none of the scanned root canal fillings were void-free. For I-voids, the volume fraction was significantly larger, but their number was lower (P=0.0007), than for S-voids. Both types of voids occurred in characteristic regions (P<0.001). I-voids occurred mainly in the apical third, while S-voids in the coronal third of the canal filling. CONCLUSIONS Within the limitations of this study, our results indicate that microtomography, with proposed semi-automatic algorithm, is a useful tools for three-dimensional quantitative evaluation of dental root canal fillings. In canals filled with thermoplastic gutta-percha and Tubli-Seal, voids at the interface between the filling and canal dentine deserve special attention due to of their periapical location, which might promote apical microleakage. Further studies might help to elucidate the clinical relevance of these results.
Experimental life‐history evolution: selection on growth form and its plasticity in a clonal plant

The growth form along the continuum from compact phalanx plants to more loosely packed guerilla plants is an important life‐history trait in clonal plants. Prerequisite for its evolution is heritable genetic variation. Starting with 102 genotypes of the stoloniferous herb Ranunculus reptans, we performed one selection experiment on spatial spread per rosette as measure of guerillaness (broad‐sense heritability 0.198) and another on plasticity in this trait in response to competition (broad‐sense heritability 0.067). After two generations, spatial spread was 36.9% higher in the high line than in the low line (realized heritability ± SE 0.149 ± 0.039). Moreover, compared with the low line genotypes of the high line had fewer rosettes, a lower proportion of flowering rosettes, a higher proportion of rooted rosettes, more branches per rosette, longer internodes and longer leaves. In the second experiment, we found no significant direct response to selection for high and low plasticity in spatial spread (realized heritability ± SE −0.029 ± 0.063), despite a significant correlated response in plasticity in the length of the first three stolon internodes. Our study indicates a high potential for further evolution of the clonal growth form in R. reptans, but not for its plasticity, and it demonstrates that the clonal growth form does not evolve independently of other clonal life‐history characteristics.