gebhart/patrepeval huggingface dataset:
Regulation of 3-ketosteroid reductase messenger ribonucleic acid levels and 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase activity in rat liver by sex steroids and pituitary hormones. (1992)

We have recently characterized three types of complementary DNA clones encoding predicted isoenzymes of the rat 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) family. Transient expression in nonsteroidogenic cells reveals that the type III isoenzyme specific for male liver does not display oxidative activity for classical substrates of 3 beta-HSD, in contrast to the two other 3 beta-HSD isoenzymes, thus showing exclusively 3-ketosteroid reductase (3-KSR) activity. In order to better understand the sex-specific control of 3 beta-HSD activity and type III 3-KSR gene expression in rat liver, we have studied in adult animals of both sexes the effect of sex steroids and hypophysectomy, pituitary implants, PRL, and GH on type III 3-KSR messenger RNA (mRNA) levels and 3 beta-HSD/delta 5-delta 4 isomerase activity as measured by the conversion of [14C]dehydroepiandrosterone into [14C] delta 4-androstenedione. Ribonuclease protection assay using types I-, II-, and III-specific complementary RNA probes reveals that type III transcripts are the only species detectable in liver RNA extracted from intact males, whereas no hybridization signal was detectable with any of the three probes in intact female liver RNA. In males, 15 days after castration, liver type III 3-KSR mRNA levels decreased by 80% compared to intact controls, whereas 3 beta-HSD activity was reduced by 48%. Administration of dihydrotestosterone (DHT) increased by 8.25-fold type III 3-KSR mRNA concentration and completely reversed the inhibitory effect of orchiectomy on 3 beta-HSD activity. In ovariectomized animals, treatment with DHT markedly increased type III 3-KSR mRNA accumulation and 3 beta-HSD activity, thus leading to values similar to those measured in intact males. Simultaneous treatment with 17 beta-estradiol almost completely abolished the stimulatory effect of DHT in female rats, whereas no significant effect was seen in males. Twenty-four days after hypophysectomy, type III 3-KSR mRNA levels were decreased by 50-55% in males, whereas in females these transcripts markedly increased from undetectable to 28-36% of the value measured in intact male rats. Treatment with DHT or 17 beta-estradiol for a period of 9 days starting 15 days after hypophysectomy had no effect in male and female rats. On the other hand, treatment with ovine PRL (1 mg, twice daily) had no effect in males but completely blocked the elevation of type III 3-KSR mRNA levels and 3 beta-HSD activity observed after hypophysectomy in females.(ABSTRACT TRUNCATED AT 400 WORDS)
Broad Spectrum Functional Activity of Structurally Related Monoanionic Au(III) Bis(Dithiolene) Complexes (2022)

The biological properties of sixteen structurally related monoanionic gold (III) bis(dithiolene/ diselenolene) complexes were evaluated. The complexes differ in the nature of the heteroatom connected to the gold atom (AuS for dithiolene, AuSe for diselenolene), the substituent on the nitrogen atom of the thiazoline ring (Me, Et, Pr, iPr and Bu), the nature of the exocyclic atom or group of atoms (O, S, Se, C(CN)<sub>2</sub>) and the counter-ion (Ph<sub>4</sub>P<sup>+</sup> or Et<sub>4</sub>N<sup>+</sup>). The anticancer and antimicrobial activities of all the complexes were investigated, while the anti-HIV activity was evaluated only for selected complexes. Most complexes showed relevant anticancer activities against Cisplatin-sensitive and Cisplatin-resistant ovarian cancer cells A2780 and OVCAR8, respectively. After 48 h of incubation, the IC<sub>50</sub> values ranged from 0.1-8 μM (A2780) and 0.8-29 μM (OVCAR8). The complexes with the Ph<sub>4</sub>P<sup>+</sup> ([<b>P</b>]) counter-ion are in general more active than their Et<sub>4</sub>N<sup>+</sup> ([<b>N</b>]) analogues, presenting IC<sub>50</sub> values in the same order of magnitude or even lower than Auranofin. Studies in the zebrafish embryo model further showed that, despite their marked anticancer effect, the complexes with [<b>P</b>] counter-ion exhibited low in vivo toxicity. In general, the exocyclic exchange of sulfur by oxygen or ylidenemalononitrile (C(CN)<sub>2</sub>) enhanced the compounds toxicity. Most complexes containing the [<b>P</b>] counter ion exhibited exceptional antiplasmodial activity against the <i>Plasmodium berghei</i> parasite liver stages, with submicromolar IC<sub>50</sub> values ranging from 400-700 nM. In contrast, antibacterial/fungi activities were highest for most complexes with the [<b>N</b>] counter-ion. Auranofin and two selected complexes [<b>P</b>][AuSBu(=S)] and [<b>P</b>][AuSEt(=S)] did not present anti-HIV activity in TZM-bl cells. Mechanistic studies for selected complexes support the idea that thioredoxin reductase, but not DNA, is a possible target for some of these complexes. The complexes [<b>P</b>] [AuSBu(=S)], [<b>P</b>] [AuSEt(=S)], [<b>P</b>] [AuSEt(=Se)] and [<b>P</b>] [AuSeiPr(=S)] displayed a strong quenching of the fluorescence intensity of human serum albumin (HSA), which indicates a strong interaction with this protein. Overall, the results highlight the promising biological activities of these complexes, warranting their further evaluation as future drug candidates with clinical applicability.
Stimulus coding rules for perceptual learning (2010)

Background: We reported previously (Kuai et al., NN2005) that perceptual learning of contrast and motion direction discrimination occurs when multi-stimuli are presented in a fixed sequence (temporal patterning), but not randomly (roving), which points to the need for proper stimulus coding for multi-stimulus learning to occur. In this study we examined the stimulus coding rules for perceptual learning with multi-stimuli. Methods: Subjects practice contrast discrimination of Gabors at multiple reference contrasts and orientation discrimination of illusory lines at multiple reference orientations in various roving and temporal pattering conditions. Results: 1) Stimulus rhythm, especially temporally evenly spaced, is necessary for temporal patterning to take effect during practice. 2) Both the encoding phase, and the slow consolidation phases as least 4 hours after each practice session, of perceptual learning are subject to roving disruption; 3) However, after completion of temporal patterned learning, performance is undisrupted by extended roving training, and instead learning is transferable to the roving condition; 4) Roving is ineffective if each stimulus is presented in a block of five or more consecutive trials; 5) Roving is also ineffective if each stimulus has a distinct identity, either due to large inter-stimulus difference, or inherited identity (i.e., cardinal/oblique orientations), or assigned identity through pre-trial letter cueing. Conclusions: Our results sketched some basic rules for stimulus encoding, consolidation, and retrieval for multi-stimulus perceptual learning. These rules may be needed because the brain needs to “tag” each stimulus, in order to switch attention to the appropriate perceptual template. Stimulus temporal patterning assists in tagging stimuli and switching attention through its rhythmic stimulus sequence. However, once the identities are learned, stimulus information can be efficiently retrieved to guide visual discrimination regardless of the stimulus temporal context.
Impact of Using Uniform Attenuation Coefficients for Heterogeneously Dense Breasts in a Dedicated Breast PET/X-Ray Scanner (2020)

We investigated PET image quantification when using a uniform attenuation coefficient (<i>μ</i>) for attenuation correction (AC) of anthropomorphic density phantoms derived from high-resolution breast CT scans. A breast PET system was modeled with perfect data corrections except for AC. Using uniform <i>μ</i> for AC resulted in quantitative errors roughly proportional to the difference between <i>μ</i> used in AC (<i>μ</i> <sub>AC</sub>) and local <i>μ</i>, yielding approximately ± 5% bias, corresponding to the variation of <i>μ</i> for 511 keV photons in breast tissue. Global bias was lowest when uniform <i>μ</i> <sub>AC</sub> was equal to the phantom mean <i>μ</i> (<i>μ</i> <sub>mean</sub>). Local bias in 10-mm spheres increased as the sphere <i>μ</i> deviated from <i>μ</i> <sub>mean</sub>, but remained only 2-3% when the <i>μ</i> <sub>sphere</sub> was 6.5% higher than <i>μ</i> <sub>mean</sub>. Bias varied linearly with and was roughly proportional to local <i>μ</i> mismatch. Minimizing local bias, e.g., in a small sphere, required the use of a uniform <i>μ</i> value between the local <i>μ</i> and the <i>μ</i> <sub>mean</sub>. Thus, biases from using uniform-<i>μ</i> AC are low when local <i>μ</i> <sub>sphere</sub> is close to <i>μ</i> <sub>mean</sub>. As the <i>μ</i> <sub>sphere</sub> increasingly differs from the phantom <i>μ</i> <sub>mean</sub>, bias increases, and the optimal uniform <i>μ</i> is less predictable, having a value between <i>μ</i> <sub>sphere</sub> and the phantom <i>μ</i> <sub>mean</sub>.
A novel approach to the analysis of squeezed-film air damping in microelectromechanical systems (2016)

Squeezed-film damping (SFD) is a phenomenon that significantly affects the performance of micro-electro-mechanical systems (MEMS). The total damping force in MEMS mainly include the viscous damping force and elastic damping force. Quality factor (Q factor) is usually used to evaluate the damping in MEMS. In this work, we measure the Q factor of a resonator through experiments in a wide range of pressure levels. In fact, experimental characterizations of MEMS have some limitations because it is difficult to conduct experiments at very high vacuum and also hard to differentiate the damping mechanisms from the overall Q factor measurements. On the other hand, classical theoretical analysis of SFD is restricted to strong assumptions and simple geometries. In this paper, a novel numerical approach, which is based on lattice Boltzmann simulations, is proposed to investigate SFD in MEMS. Our method considers the dynamics of squeezed air flow as well as fluid-solid interactions in MEMS. It is demonstrated that Q factor can be directly predicted by numerical simulation, and our simulation results agree well with experimental data. Factors that influence SFD, such as pressure, oscillating amplitude, and driving frequency, are investigated separately. Furthermore, viscous damping and elastic damping forces are quantitatively compared based on comprehensive simulation. The proposed numerical approach as well as experimental characterization enables us to reveal the insightful physics of squeezed-film air damping in MEMS.
Prototype of a portable platform for ECG monitoring and diagnostic applications (2008)

This paper describes the prototype for a portable system that records and analyses electrocardiography signals in real time. The purpose of the system is to monitor patients during normal activity to help physicians to diagnose the long QT syndrome and alerts the patient to prevent sudden death. The system consists of a recording system for three leads electrocardiography signals and an algorithm implemented on a board based on a low power microcontroller. The system has been tested in non-pathologic subjects showing accurate values for the heart rate and QTc factor. The algorithm has also been tested satisfactory with created signals simulating pathologic and non-pathologic cases. It was also tested with 10 patients from a standard database showing satisfactory results except for signals where any of the characteristic waves of the ECG is not present. .
Mechanism of bicarbonate absorption and its relationship to sodium transport in the human jejunum (1970)

Using a constant perfusion technique, sodium and bicarbonate absorption was studied in human subjects. The following observations were made on sodium absorption from saline solution: (a) the rate of sodium absorption is markedly influenced by bulk water flow, (b) when net water flow is zero, sodium absorption is zero if there are no concentration gradients between plasma and lumen that favor net NaCl diffusion; and (c) the PD between abraded skin and jejunal lumen is near zero when saline is perfused and does not change with partial substitution of sulfate or bicarbonate for chloride. Based on these observations, we conclude that sodium absorption from saline is entirely passive in the human jejunum. On the other hand, in the presence of bicarbonate sodium is absorbed actively against electrochemical gradients. The mechanism of the link between bicarbonate and sodium absorption was studied in normal subjects and in 11 patients with pernicious anemia; the latter were chosen because they do not secrete gastric acid which can react with bicarbonate in the jejunal lumen. We observed that bicarbonate absorption (a) occurs against steep electrochemical gradients, (b) does not generate a potential difference between abraded skin and jejunal lumen, (c) is inhibited by acetazolamide, and (d) generates a high CO2 tension in jejunal fluid. These observations suggest that bicarbonate absorption is mediated by active hydrogen secretion, rather than by bicarbonate ion transport per se, and that the link between sodium and bicarbonate transport is best explained by a sodium-hydrogen exchange process.
Targeting host cells harbouring viruses with radiolabeled antibodies (2007)

Existing antiviral therapies produce a therapeutic effect by suppressing viral replication and reducing viral burden and the associated inflammatory reaction. However, infection with many viruses results in chronic infections that cannot be eradicated by the immune response or available antiviral drugs. As viruses are obligate intracellular pathogens, it should be possible to eradicate chronic infections by targeting and eliminating the infected host cells. Radioisotope-conjugated antibodies that specifically bind viral antigens can deliver cytotoxic radiation to virally infected cells. This approach was recently shown to target and eliminate HIV-1-infected cells in vitro and in mouse models, and provides a new approach for eliminating virally infected cells.
Resilient Low Voltage Accelerators for High Energy Efficiency (2019)

Low voltage architecture and design are key enablers of high throughput per watt in heterogeneous, accelerator-rich many-core designs. However, such low voltage operation poses significant challenges because of difficulties in achieving reliable functionality of on-chip memories, particularly SRAMs at these design points. In this paper, we present a technique of low-voltage neural network acceleration, where the embedded SRAM architecture is equipped with a novel application-aware supply voltage boosting capability. This technique mitigates low-voltage induced failures, while enabling Very low voltage (VLV) <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sup> operation during most of the application run, resulting in substantial improvement in net energy efficiency. We present a framework to evaluate the impact of low-voltage SRAM errors on machine learning applications and characterize trade-offs between output inference accuracy and energy efficiency in our application-programmable supply boosted SRAM architecture. Using the proposed technique we push the limits on the minimum operable voltage (V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">min</sub> ) for the desired output quality. As a proof of concept, we demonstrate these techniques on Dante, a Deep Neural Network (DNN) accelerator chip taped out in state-of-the art 14nm technology.
Vasodilator effects of adrenomedullin on small pulmonary arteries and veins in anaesthetized cats (1997)

1. This study was conducted to determine adrenomedullin (AM) action sites in the pulmonary vascular bed and the relation between its vasodilator effects and vascular tone. Moreover, an examination was made into whether calcitonin gene-related peptide (CGRP) receptors mediate pulmonary vasodilatations induced by AM. To this end, we directly measured internal diameter (i.d.) changes in small pulmonary arteries and veins (100-1100 microns i.d.) by use of an X-ray television system on the in vivo cat lung. 2. Under control (resting vascular tone) conditions, AM injections into the left main pulmonary artery caused dose-related i.d. increases in both small arteries and veins. The mean i.d. increase of the 100-1100 microns arteries (4 +/- 1, 11 +/- 2, and 17 +/- 2% with 0.01, 0.1, and 1 nmol kg-1 AM, respectively) was significantly larger than that for the veins (1 +/- 1, 5 +/- 2, and 7 +/- 2% with 0.01, 0.1 and 1 nmol kg-1 AM, respectively) whatever the injected dose of AM. 3. When unilobar hypoxia (5% O2) had decreased the i.d. of the 100-1100 microns arteries and veins by 16 +/- 3 and 6 +/- 3%, respectively, AM (0.1 nmol kg-1) was able to induce significantly larger i.d. increases in the arteries (28 +/- 3%) and veins (11 +/- 3%) than those under control conditions. 4. The AM-induced i.d. response pattern in the serially connected pulmonary arteries was quite different from that induced by CGRP; AM caused a greater increase in smaller vessels (100-500 microns) than in larger vessels (500-1100 microns). In the case of CGRP, a greater increase was observed in the larger vessels. 5. CGRP8-37 (100 nmol kg-1, i.v., followed by a continuous infusion of 0.2 nmol kg-1 min-1) had no significant effect on the i.d. increase induced by AM (0.1 nmol kg-1) in any serial segments of the arteries and veins. 6. The results indicate that, in the cat, AM induces greater vasodilatation in small pulmonary arteries and lesser vasodilatation in small veins, the maximum dilatation being in the more peripheral arterial segment (100-500 microns). The vasodilator effect of AM was enhanced when vascular tone was elevated. The data suggest that the AM-induced pulmonary vasodilatation is not mediated by CGRP receptors but by its own specific receptor.
The in vitro evaluation of nucleoside analogues as probes for use in the noninvasive diagnosis of herpes simplex encephalitis. (1988)

1-(2-Deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil (FIAU) and the 5-iodo (FIRU), 5-bromo (FBrRU), 5-chloro (FClRU) and 5-fluoro (FFRU) analogues of 1-(2-deoxy-2-fluoro-beta-D-ribofuranosyl)uracil were examined in four in vitro tests designed to evaluate their potential as radiopharmaceuticals in a non-invasive diagnostic test for herpes simplex encephalitis (HSE). The tests involved, (a) cellular uptake studies--which showed that all five nucleosides are selectively trapped in rabbit kidney cells infected with herpes simplex virus, type I, which codes for its own thymidine kinase; (b) incubation studies--which showed that, in human platelets, FIAU, FIRU and FFRU are not degraded by thymidine phosphorylase (an enzyme which catalyzes the glycosidic bond cleavage of physiological nucleosides); (c) a transport study, using mouse erythrocytes--which indicated that all five nucleosides have good affinity for a NBMPR-sensitive nucleoside transporter, with inhibition constants (Ki values in the range of 0.177-0.41; and (d) determination of octanol/water partition coefficients--which (log P = -0.14 to -1.67) indicated that FIAU is the most lipophilic of the five compounds studied, and may therefore cross the blood-brain barrier most readily. We conclude from the results that FIAU is the most promising compound for further evaluation in HSE animal models. The combination of tests described in this study provide a useful screening protocol for evaluation of other nucleoside analogues of potential use in a diagnostic test for HSE.
Failed Metal-on-Metal Hip Arthroplasties: A Spectrum of Clinical Presentations and Operative Findings (2010)

Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
Causal Mediation in a Survival Setting with Time-Dependent Mediators (2012)

The effect of an expsore on an outcome of interest is often mediated by intermediate variables. The goal of causal mediation analysis is to evaluate the role of these intermediate variables (mediators) in the causal effect of the exposure on the outcome. In this paper, we consider causal mediation of a baseline exposure on a survival (or time-to-event) outcome, when the mediator is time-dependent. The challenge in this setting lies in that the event process takes places jointly with the mediator process; in particular, the length of the mediator history depends on the survival time. As a result, we argue that the definition of natural effects in this setting should be based on only blocking those paths from treatment to mediators that are not through the survival history. We propose to use a stochastic interventions (SI) perspective, introduced by Didelez, Dawid, and Geneletti (2006), to formulate the causal mediation analysis problem in this setting. Under this formulation, the mediators are regarded as intervention variables, onto which a given counterfactual distribution is enforced. The natural direct and indirect effects can be defined analogously to the ideas in Pearl (2001). In particular, they also allow for a total effect decomposition and an interpretation of the natural direct effect as a weighted average of controlled direct effects. The statistical parameters that should arise are defined nonparametrically; therefore, they have meaningful interpretations, independent of the causal formulations and assumptions. We present a general semiparametric inference framework for these parameters. Using their efficient influence functions, we develop semiparametric efficient and robust targeted substitution-based (TMLE) and estimating-equation-based (A-IPTW) estimators. An IPTW estimator and g-computation estimator will also be presented.
High-Quality Soft Video Delivery With GMRF-Based Overhead Reduction (2017)

Soft video delivery, i.e., analog video transmission, has been proposed to provide high video quality in unstable wireless channels. However, existing analog schemes need to transmit a significant amount of metadata to a receiver for power allocation and decoding operations causing large overhead and quality degradation due to rate and power losses. To reduce the overhead while keeping the video quality high, we propose a new analog transmission scheme. Our scheme exploits a Gaussian Markov random field for modeling video sequences to significantly reduce the required amount of metadata, which are obtained by fitting into the Lorentzian function. Our scheme achieves not only reduced overhead but also improved video quality, by using the fitting function and parameters for metadata. Evaluations using several test video sequences demonstrate that the proposed scheme reduces overhead by 99.7% with 1.2-dB improvement of video quality (in terms of peak signal-to-noise ratio) compared to the existing analog video transmission scheme. We also investigate the impact of bandwidth limitation, showing a significant gain up to 2.7 dB for narrow-band systems.
Molecular Imaging-Guided Theranostics and Personalized Medicine (2013)

Molecular imaging science has been focused on imaging guidance in the areas of targeting epigenetic abnormalities and tumor microenvironment in overcoming resistance in cancers. The use of image-guided technologies to select patient for personalized therapy and to monitor therapeutic outcomes is the focus of this special issue. For instance, mutations in the kinase domain of epidermal growth factor receptor (EGFR) have been associated with clinical responsiveness using tyrosine kinase inhibitors for nonsmall cell lung cancer (NSCLC). S. H.-H. Yeh et al. reported the feasibility of using morpholino-[I-124]IPQA as an in vivo PET imaging probe for the expression of different EGFR mutants in NSCLC. Their micro-PET imaging along with biologic validation indicated that [I-124]IPQA derivative might be a useful probe in selecting the patients with NSCLC for tyrosine kinase inhibitor therapy.