gebhart/patrepeval huggingface dataset:
Preliminary in vivo pharmacokinetic and pharmacodynamic evaluation of a novel calcineurin-independent inhibitor of NFAT (2004)

Abstract A-285222 (A-285) is a bistrifluoromethyl-pyrazole (BTP), a novel class of immunosuppressive agents that inhibit NFAT activity in vitro in human and non-human primate cells through a calcineurin-independent mechanism. In this preliminary study, we treated cynomolgus monkeys with different doses of A-285 for several days. Blood was collected from all animals at different times during the study. From these samples, plasma concentrations of A-285 were measured by liquid chromatography/mass spectrometry (LC/MS), and intracellular T-cell production of the cytokines IL-2, IFN-γ, and TNF-α was quantified by flow cytometry using a mitogen-stimulated whole blood assay. Marked inhibition of cytokine production occurred after administration of the first dose of A-285, and this effect was comparable to that of cyclosporine. While neurological toxic side effects were seen when the plasma concentration of A-285 exceeded 4 μg/ml, at lower plasma levels the drug was well tolerated over 2 weeks and its pharmacodynamic effects were sustained throughout this time.
Regulation of rat ornithine decarboxylase mRNA translation by its 5'-untranslated region. (1990)

Ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, is a highly inducible protein whose expression involves a complex and variable array of regulatory mechanisms. We investigated the influence of the 5'-untranslated region (5'UTR) of the rat ODC mRNA on translation of the mRNA in a cell-free system and in cultured mammalian cells. ODC mRNA containing the full-length 5'UTR was translated in reticulocyte lysates at approximately 5% of the rate of mRNA containing no ODC 5' leader sequences. The complete 5'UTR inhibited expression of a heterologous gene product, human growth hormone, to the same extent in cultured mammalian cells. Furthermore, the 5'-most 130 bases of the rat ODC 5'UTR, a conserved G/C-rich region predicted to form a stable stem-loop structure (delta G = -68 kcal/mol), repressed translation to the same extent as the entire 5'UTR, both in the lysates and in intact cells. The 3'-most 160 bases of the 5'UTR, containing a small upstream open reading frame, decreased expression by 50-65% both in vitro and in intact cells, compared with controls lacking any ODC 5'UTR sequences. Mutation of the initiation codon AUG beginning this upstream open reading frame to GCG restored expression to rates equivalent to those seen in constructions containing no ODC 5'UTR sequences. We conclude that the rat ODC mRNA 5'UTR can inhibit translation of ODC mRNA both in vitro and in vivo, and that the predicted stem-loop structure at the 5' end of the 5'UTR is both necessary and sufficient for this inhibition.
A feasible path for the use of ferromagnetic josephson junctions in quantum circuits: The ferro-transmon (2023)

We discuss the capabilities of ferromagnetic (F) Josephson junctions (JJs) in a variety of layouts and configurations. The main goal is to demonstrate the potential of these hybrid JJs to disclose new physics and the possibility to integrate them in superconducting classical and quantum electronics for various applications. The feasible path towards the use of ferromagnetic Josephson junctions in quantum circuits starts from experiments demonstrating macroscopic quantum tunneling in NbN/GdN/NbN junctions with ferro-insulator barriers and with triplet components of the supercurrent, supported by a self-consistent electrodynamic characterization as a function of the barrier thickness. This has inspired further studies on tunnel ferromagnetic junctions with a different layout and promoted the first generation of ferromagnetic Al-based JJs, specifically Al/AlOx/Al/Py/Al. This layout takes advantage of the capability to integrate the ferromagnetic layer in the junction without affecting the quality of the superconducting electrodes and of the tunnel barrier. The high quality of the devices paves the way for the possible implementation of Al tunnel-ferromagnetic JJs in superconducting quantum circuits. These achievements have promoted the notion of a novel type of qubit incorporating ferromagnetic JJs. This qubit is based on a transmon design featuring a tunnel JJ in parallel with a ferromagnetic JJ inside a SQUID loop capacitively coupled to a superconducting readout resonator. The effect of an external RF field on the magnetic switching processes of ferromagnetic JJs has been also investigated.
The scent of an ion: calcium-sensing and its roles in health and disease. (1996)

The recent cloning of G protein-coupled extracellular Ca2+ (Ca2+o)-sensing receptors from bovine (and human) parathyroid and rat kidney (and brain) has clearly shown that Ca2+o can function as a 'first messenger'. The physiological relevance of this receptor in Ca2+o homeostasis in man has been demonstrated by the identification both of 'inactivating' and of 'activating' mutations in this Ca2+o-sensing receptor, which result in hypercalcemic and hypocalcemic phenotypes, respectively. The molecular mechanisms involved in extracellular calcium 'sensing' in the kidney are just beginning to emerge but are already suggesting new and novel mechanisms for linking Ca2+ (and Mg2+) and water excretion. The latter inter-relationship appears to be crucial because maximal water conservation during periods of increased urinary Ca2+ or Mg2+ loss (e.g. due to increased dietary intake of these solutes) would increase urinary divalent cation concentration and enhance the risk of crystal/stone formation. The interactions among Ca2+, NaCl and water handling in the distal nephron and collecting duct may provide mechanisms for integrating and balancing water and divalent mineral loss, minimizing the risk of stone formation (a 'trade-off' of water conservation for Ca2+ or Mg2+ loss). Research over the next few years should greatly expand our understanding of the roles played by this Ca2+o-sensor both in divalent mineral excretion and in water metabolism as well as in other tissues (e.g. in the central nervous system).
Temporal Evolution of Clinical Parameters before Death in Dialysis Patients: A New Concept (2009)

In their final 3 months of life, HD patients experience a marked decrease in body weight and serum albumin levels. A better understanding of dynamic patterns of key variables before death may be useful in developing processes which alert medical caregivers to patients at increased risk, in order to institute timely diagnostic and therapeutic interventions.
Single molecule array (Simoa) assay with optimal antibody pairs for cytokine detection in human serum samples (2015)

Concentrations of cytokines in bodily fluids reflect the physiological or pathological state of the patient and can be used for prognosis, disease diagnosis or for monitoring therapeutic efficacy. However, in the bodily fluids of healthy or sub-healthy individuals, many cytokines are present at concentrations that are near or below the detection limits of current methods. Here we selected antibody pairs to be employed in the single molecule array (Simoa) assay for ten cytokines including GM-CSF, TNF-α, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, and IL-10. The limits of detection (LODs) obtained were as low as 90 aM-6 fM. These assays allow detection of cytokines in healthy human serum samples at levels significantly below the detection limits of conventional ELISA assays. We provide detailed antibody pair information as well as the concentration profiles of ten cytokines in healthy human serum to serve as reference data for further ultrasensitive immunoassay development and future clinical applications.
An Unequal Error Protection Framework for DVB-H and Its Application to Video Streaming (2008)

In this paper, an unequal error protection (UEP) scheme is proposed for DVB-H based on its link layer forward error correction. The scheme preserves the existing DVB-H protocol stack and maintains its original time diversity. The UEP scheme is further applied to DVB-H video streaming service. The H.264 based temporal scalable coding is employed to facilitate UEP application and provides a set of UEP configurations to accommodate different channel conditions. Experimental results show graceful video quality degradation provided by the proposed framework.
1.5-mJ Cr:ZnSe Chirped Pulse Amplifier Seeded by a Kerr-Lens Mode-Locked Cr:ZnS oscillator (2019)

We report a 1-kHz, 1.5 mJ Cr:ZnSe chirped pulse amplifier with 140 fs pulse width, 9.5 GW peak power at 2.4 µm central wavelength. The amplifier is seeded with a commercial few-cycle Cr:ZnS oscillator.
Healthcare worker safety program in a coronavirus disease 2019 (COVID-19) alternate care site: The Javits New York Medical Station experience (2022)

A well-designed and implemented HCW safety plan can minimize the risk of SARS-CoV-2 infection for HCWs. The lessons learned from operating the nation's largest COVID-19 alternate care site can be adapted to other environments during public health emergencies.
Self-Organization Properties of CSMA/CA Systems and Their Consequences on Fairness (2009)

Decentralized medium access control schemes for wireless networks based on CSMA/CA, such as the IEEE 802.11 protocol, are known to be unfair. In multihop networks, they can even favor some links to such an extent that the others suffer from virtually complete starvation. This observation has been reported in quite a few works, but the factors causing it are still not well understood. We find that the capture effect and the relative values of the receive and carrier sensing ranges play a crucial role in the performance of these protocols. Using a simple Markovian model, we show that an idealized CSMA/CA protocol suffers from starvation when the receiving and sensing ranges are equal, but quite surprisingly that this unfairness is reduced or even disappears when these two ranges are sufficiently different. We also show that starvation has a positive counterpart, namely organization. When its access intensity is large the protocol organizes the transmissions in space in such a way that it maximizes the number of concurrent successful transmissions. We obtain exact formula for the so-called spatial reuse of the protocol on large line networks.
Marburg I Polymorphism of Factor VII–Activating Protease (2003)

In concert with other genetic and acquired conditions known to interfere with coagulation or fibrinolysis, the Marburg I polymorphism of FSAP, which attenuates its capacity to activate prourokinase, is a significant risk predictor for the evolution and progression of carotid stenosis.
Genetic transformation of Streptococcus pneumoniae by DNA cloned into the single-stranded bacteriophage f1 (1983)

A Staphylococcus aureus plasmid derivative, pFB9, coding for erythromycin and chloramphenicol resistance was cloned into the filamentous Escherichia coli phage f1. Recombinant phage-plasmid hybrids, designated plasmids, were isolated from E. coli and purified by transformation into Streptococcus pneumoniae. Single-stranded DNA was prepared from E. coli cells infected with two different plasmids, fBB101 and fBB103. Introduction of fully or partially single-stranded DNA into Streptococcus pneumoniae was studied, using a recipient strain containing an inducible resident plasmid. Such a strain could rescue the donor DNA marker. Under these marker rescue conditions, single-stranded fBB101 DNA gave a 1% transformation frequency, whereas the double-stranded form gave about a 31% frequency. Transformation of single-stranded fBB101 DNA was inhibited by competing double-stranded DNA and vice versa, indicating that single-stranded DNA interacts with the pneumococcus via the same binding site as used by double-stranded DNA. Heteroduplexed DNA containing the marker within a 70- or 800-base single-stranded region showed only slightly greater transforming activity than pure single-stranded DNA. In the absence of marker rescue, both strands of such imperfectly heteroduplexed DNA demonstrated transforming activity. Pure single-stranded DNA demonstrated low but significant transforming activity into a plasmid-free recipient pneumococcus.
MEDU-48. MRI TEXTURAL FEATURES CAN DIFFERENTIATE PEDIATRIC POSTERIOR FOSSA TUMORS (2017)

BACKGROUND: Medulloblastoma (MB), Ependymomas (EP), & Gliomas are the most common posterior fossa (PF) tumors in children. Reliable, non-invasive biomarker that can distinguish these tumor types would significantly aid clinical management. We recently developed a new computerized descriptor, CoLlAGe, that distinguishes subtly-different pathologies in adult brain tumors. CoLlAGe measures the orientation of local intensity gradients as an estimate of lesion heterogeneity. In this work, we hypothesize that CoLlAGe can identify subtle micro-architectural differences between MB, EP and Glioma on routine MRI scans. METHODS: A retrospective cohort of 59 studies (MB = 22, EP = 12, Glioma = 25) was acquired. After registration, scans were age normalized, skull-stripped, and corrected for intensity inhomogeneities. Every lesion was then expert delineated to obtain a region of interest (ROI). 52 CoLlAGe features were extracted from every ROI for every MRI sequence (T1w, T2w, FLAIR). Wilcoxon rank sum test was used to identify top 10 CoLlAGe features within a training set of 30 patients (MB = 11, EP = 6, G = 13), for differentiating MB from (EP+Glioma), & Glioma from (MB+EP). Using top features, random forest classifiers were built for every sequence, and validated on an independent set of 29 studies (MB = 11, EP = 6, G = 12) by using area under receiver operating characteristic curve (AUROC). RESULTS: On the independent set, we found that sum variance and entropy of CoLlAGe (p< 0.002) on T2w protocol could reliably distinguish MB from (EP+Gliomas) (AUROC = 0.88), and entropy and sum average of CoLlAGe on T2w (p < 0.0003) could differentiate Gliomas from (MB+EP) (AUROC = 0.72). CONCLUSION: Our results suggest that entropy feature of CoLlAGe, a measure of tumor heterogeneity, enabled discrimination of MB from (EP+Glioma). Prospective validation of these features in a larger cohort may improve personalized treatment management for PF tumors.
Ex vivo studies of the effect of high-intensity focused ultrasound on whole human blood (1998)

A surgical application of high-intensity focused ultrasound (HIFU) is hemostatis. In this application, both tissue and blood will be subjected to HIFU. What will happen to blood? The intent of this study is to explore via experiment some of the bioeffects of HIFU on whole human blood. A 1.1-MHz piezoceramic source with a 60-mm radius of curvature and 100-mm aperture was used. Special acoustically transparent containers were made of handmade, low-density polyethylene tubing. Phenomena studied included hemolysis, morphologic changes in erythrocytes, white blood cell differential, and platelet activation, all as a function of acoustic intensity and dosage. Intensities up to 6000 W/cm2 were used in cw pulses of one second. The bioeffects noted above were correlated with temperature and a passive acoustic measure of bubble activity within the blood created by the ultrasound. Under the acoustic conditions considered for this work, nonthermal acoustic effects were most strongly associated with bioeffects. [Work sponsored by DARPA.]
Tree Growth Based Optimization Algorithm for Parameter Extraction of Different Models of Photovoltaic Cells and Modules (2020)

Among all renewable energy sources, solar cells are considered the most popular solution for a clean source of energy and have a wide range of applications from few watts to Megawatt industrial and domestic loads. Building a precise mathematical model based on nonlinear equations for solar cells as well as photovoltaic (PV) modules is an essential issue for reasonable performance assessment, control and optimal operation of PV energy systems. In the current study, a novel optimization algorithm, Tree Growth Algorithm (TGA), is applied for accurate and efficient extraction of the unknown solar cell and PV module parameters. TGA is applied for estimating the unidentified parameters of PV models. Single diode model (SDM), double diode model (DDM) and three diode model (TDM) are investigated in the mathematical models of both solar cells and PV modules. The obtained results from the application of TGA to achieve this objective are compared with different algorithms reported in the literature. Moreover, the results demonstrated that the proposed algorithm of TGA superior to other reported methods. The good matching of the I-V characteristic curve of the computed parameters with those of the measured data from the manufacturer's PV modules/cells datasheet proved that the proposed TGA may function as a competitor to the methods provided in literature for parameters' identification of PV of solar cells.
82. Mapping the Humoral Immune Response to AAV by Molecular Docking and Cryo-Electron Microscopy for the Design of Next-Generation AAV Vectors (2016)

Despite constant improvements in gene therapy with AAV vectors, including use of new serotypes, routes of administration, and transgene cassette engineering, immune responses continue to be a major obstacle to therapeutic translation. Neutralizing antibodies (NAb) against the capsid generated by prior viral infection or AAV vector administration significantly reduce not only the effective patient population but also the overall efficacy of an AAV-based gene therapy. Here, by cloning out and evaluating anti-AAV antibodies from singly-sorted memory B cells from seropositive individuals, we have designed an approach that allows us to look at the humoral immune response globally, to hone in on the immunogenic regions of the capsid itself, and to compare responses between individuals in an unbiased and therapeutically-relevant setting. In this study, we screened a panel of 30 normal human donors, selected one with high pre-existing NAb titers (1:320 for AAV2, 1:40 for AAV3B), then sorted out switched memory B cells by negative selection, seeding on irradiated ms3T3-CD40L feeder cells and culturing for 2 weeks in the presence of IL-2 and IL-21. Following supernatant screening for anti-AAV antibody production, over 100 AAV-reactive clones were identified. After isolation and cloning using nested PCR, antibodies were evaluated for AAV capsid binding as well as neutralizing capacity. To date, all antibodies demonstrated binding to AAV2 and AAV3B as well as a panel of additional AAV serotypes (8, 9, rh10, rh32.33), suggesting that AAV-binding, yet non-neutralizing antibodies may possess broad serotype specificity. To identify the epitopes for these anti-AAV antibodies, we first took a high-throughout, predictive approach. Antibody variable region sequences were placed into a generic antibody scaffold and their three-dimensional structure modeled using Kotai Antibody Builder and RosettaAntibody followed by validation using COOT. The resulting structures were then iteratively docked onto the published structure of AAV3B using PIPER to identify the most energetically-favorable binding conformation. Thus far, the vast majority of footprint residues lie in variable regions of the capsid comprising and surrounding the 3-fold spikes. For a number of antibodies, initial prediction-directed capsid alanine scanning experiments have shown decreased antibody binding at the predicted residues, supporting the use of this approach. More comprehensive mutagenesis experiments are underway to further validate the approach and more completely map immunogenic epitopes of the AAV capsid proteins. In addition, cryo-EM analysis is currently underway for a number of these Fab-AAV complexes for additional, direct observation of the repertoire of binding footprints. These studies will provide information critical to understanding the antibody response to AAV and guide future attempts to rationally design next-generation capsids that are able to evade the anti-AAV antibody response.
Cav3.2 T-type calcium channels shape electrical firing in mouse Lamina II neurons (2019)

The T-type calcium channel, Cav3.2, is necessary for acute pain perception, as well as mechanical and cold allodynia in mice. Being found throughout sensory pathways, from excitatory primary afferent neurons up to pain matrix structures, it is a promising target for analgesics. In our study, Cav3.2 was detected in ~60% of the lamina II (LII) neurons of the spinal cord, a site for integration of sensory processing. It was co-expressed with Tlx3 and Pax2, markers of excitatory and inhibitory interneurons, as well as nNOS, calretinin, calbindin, PKCγ and not parvalbumin. Non-selective T-type channel blockers slowed the inhibitory but not the excitatory transmission in LII neurons. Furthermore, T-type channel blockers modified the intrinsic properties of LII neurons, abolishing low-threshold activated currents, rebound depolarizations, and blunting excitability. The recording of Cav3.2-positive LII neurons, after intraspinal injection of AAV-DJ-Cav3.2-mcherry, showed that their intrinsic properties resembled those of the global population. However, Cav3.2 ablation in the dorsal horn of Cav3.2<sup>GFP-Flox</sup> KI mice after intraspinal injection of AAV-DJ-Cav3.2-Cre-IRES-mcherry, had drastic effects. Indeed, it (1) blunted the likelihood of transient firing patterns; (2) blunted the likelihood and the amplitude of rebound depolarizations, (3) eliminated action potential pairing, and (4) remodeled the kinetics of the action potentials. In contrast, the properties of Cav3.2-positive neurons were only marginally modified in Cav3.1 knockout mice. Overall, in addition to their previously established roles in the superficial spinal cord and in primary afferent neurons, Cav3.2 channel appear to be necessary for specific, significant and multiple controls of LII neuron excitability.
Serpentine geometry for enhanced performance of nanometer-thin platinum bolometers (2013)

We report on the modeling, fabrication and characterization of a new serpentine geometry for platinum bolometers realized with plasma-enhanced atomic layer deposition (PEALD). The measured responsivity of 7.5 · 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">7</sup> VW <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> A <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> of the proposed structure is almost four times higher than that of previously published PEALD deposited platinum bolometers with a traditional square absorber design [1]. This improvement was achieved without increasing the sensor's footprint or fabrication complexity.
Hacking Wikipedia for Hyponymy Relation Acquisition (2008)

This paper describes a method for extracting a large set of hyponymy relations from Wikipedia. The Wikipedia is much more consistently structured than generic HTML documents, and we can extract a large number of hyponymy relations with simple methods. In this work, we managed to extract more than 1.4 × 106 hyponymy relations with 75.3% precision from the Japanese version of the Wikipedia. To the best of our knowledge, this is the largest machine-readable thesaurus for Japanese. The main contribution of this paper is a method for hyponymy acquisition from hierarchical layouts in Wikipedia. By using a machine learning technique and pattern matching, we were able to extract more than 6.3 × 105 relations from hierarchical layouts in the Japanese Wikipedia, and their precision was 76.4%. The remaining hyponymy relations were acquired by existing methods for extracting relations from definition sentences and category pages. This means that extraction from the hierarchical layouts almost doubled the number of relations extracted. 1