gebhart/patrepeval huggingface dataset:
Thrombopoietin receptor–independent stimulation of hematopoietic stem cells by eltrombopag (2018)

Eltrombopag (EP), a small-molecule thrombopoietin receptor (TPO-R) agonist and potent intracellular iron chelator, has shown remarkable efficacy in stimulating sustained multilineage hematopoiesis in patients with bone marrow failure syndromes, suggesting an effect at the most immature hematopoietic stem and multipotent progenitor level. Although the functional and molecular effects of EP on megakaryopoiesis have been studied in the past, mechanistic insights into its effects on the earliest stages of hematopoiesis have been limited. We investigated the effects of EP treatment on hematopoietic stem cell (HSC) function using purified primary HSCs in separation-of-function mouse models, including a TPO-R-deficient strain, and stem cells isolated from patients undergoing TPO-R agonist treatment. Our mechanistic studies showed a stimulatory effect on stem cell self-renewal independently of TPO-R. Human and mouse HSCs responded to acute EP treatment with metabolic and gene expression alterations consistent with a reduction of intracellular labile iron pools that are essential for stem cell maintenance. Iron preloading prevented the stem cell stimulatory effects of EP. Moreover, comparative analysis of stem cells in the bone marrow of patients receiving EP showed a marked increase in the number of functional stem cells compared to patients undergoing therapy with romiplostim, another TPO-R agonist lacking an iron-chelating ability. Together, our study demonstrates that EP stimulates hematopoiesis at the stem cell level through iron chelation-mediated molecular reprogramming and indicates that labile iron pool-regulated pathways can modulate HSC function.
Identification of the New Isoforms of Mouse Myelin Basic Protein: The Existence of Exon 5a (1991)

Myelin basic protein (MBP) is a major constituent in the myelin of the CNS. In mice, five forms of MBPs (14 kDa, two types of 17 kDa, 18.5 kDa, and 21.5 kDa) encoded by separate mRNAs have been identified based on cDNA cloning studies. These mRNAs are considered to be produced by alternative splicing from a single gene composed of seven exons. Here we report the existence of two novel MBP mRNAs encoding 19.7-kDa and 21-kDa MBPs identified by cDNA cloning using the polymerase chain reaction. Both of these MBPs contain a sequence of a previously unidentified exon of 66 nucleotides, which was mapped to be just 5' of exon 5 in the MBP gene. MBP mRNAs containing this novel exon (exon 5a) belong to a minor population in the whole brain and PNS and are somewhat enriched in the spinal cord. Exon 5a encodes a very hydrophobic segment rich in valine residues, which presumably forms a beta-pleated sheet.
An Oral Vaccine Against NMDAR1 with Efficacy in Experimental Stroke and Epilepsy (2000)

The brain is generally considered immunoprivileged, although increasing examples of immunological responses to brain antigens, neuronal expression of major histocompatibility class I genes, and neurological autoimmunity have been recognized. An adeno-associated virus (AAV) vaccine generated autoantibodies that targeted a specific brain protein, the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor. After peroral administration of the AAV vaccine, transgene expression persisted for at least 5 months and was associated with a robust humoral response in the absence of a significant cell-mediated response. This single-dose vaccine was associated with strong anti-epileptic and neuroprotective activity in rats for both a kainate-induced seizure model and also a middle cerebral artery occlusion stroke model at 1 to 5 months following vaccination. Thus, a vaccination strategy targeting brain proteins is feasible and may have therapeutic potential for neurological disorders.
High frequency reconstruction for band-limited audio signals (2003)

Current existing digital audio signals are always restricted by sampling rates and bandwidth fit for the various storages and communication bandwidth. Take for example the widely spread mp3 tracks encoded by the standard MPEG1 layer 3. The audio bandwidth in MP3 is restricted to 16 kHz due to the protocols constraints defined. This paper presents the method to reconstruct the lost high frequency components from the bandlimited signals. Both the subjective and objective measures have been conducted and shown the better quality. Especially, the important objective measurement by the perceptual evaluation of audio quality system, which is the recommendation system by ITU-R Task Group 10/4 has proven a significant quality improvement. 1.
Coplanar waveguide feeds for phased array antennas (1991)

The design and performance is presented of the following coplanar waveguides (CPW) microwave distribution networks for linear as well as circularly polarized microstrip patches and dipole arrays: (1) CPW/microstrip line feed; (2) CPW/balanced stripline feed; (3) CPW/slotline feed; (4) grounded CPW/balanced coplanar stripline feed; and (5) CPW/slot coupled feed. Typical measured radiation patterns are presented, and their relative advantages and disadvantages are compared.
ABT-378, a Highly Potent Inhibitor of the Human Immunodeficiency Virus Protease (1998)

The valine at position 82 (Val 82) in the active site of the human immunodeficiency virus (HIV) protease mutates in response to therapy with the protease inhibitor ritonavir. By using the X-ray crystal structure of the complex of HIV protease and ritonavir, the potent protease inhibitor ABT-378, which has a diminished interaction with Val 82, was designed. ABT-378 potently inhibited wild-type and mutant HIV protease (Ki = 1.3 to 3.6 pM), blocked the replication of laboratory and clinical strains of HIV type 1 (50% effective concentration [EC50], 0.006 to 0.017 microM), and maintained high potency against mutant HIV selected by ritonavir in vivo (EC50, </=0. 06 microM). The metabolism of ABT-378 was strongly inhibited by ritonavir in vitro. Consequently, following concomitant oral administration of ABT-378 and ritonavir, the concentrations of ABT-378 in rat, dog, and monkey plasma exceeded the in vitro antiviral EC50 in the presence of human serum by >50-fold after 8 h. In healthy human volunteers, coadministration of a single 400-mg dose of ABT-378 with 50 mg of ritonavir enhanced the area under the concentration curve of ABT-378 in plasma by 77-fold over that observed after dosing with ABT-378 alone, and mean concentrations of ABT-378 exceeded the EC50 for >24 h. These results demonstrate the potential utility of ABT-378 as a therapeutic intervention against AIDS.
Identification of the Antithrombin III Heparin Binding Site (1997)

The heparin binding site of the anticoagulant protein antithrombin III (ATIII) has been defined at high resolution by alanine scanning mutagenesis of 17 basic residues previously thought to interact with the cofactor based on chemical modification experiments, analysis of naturally occurring dysfunctional antithrombins, and proximity to helix D. The baculovirus expression system employed for this study produces antithrombin which is highly similar to plasma ATIII in its inhibition of thrombin and factor Xa and which resembles the naturally occurring beta-ATIII isoform in its interactions with high affinity heparin and pentasaccharide (Ersdal-Badju, E., Lu, A., Peng, X., Picard, V., Zendehrouh, P., Turk, B., Björk, I., Olson, S. T., and Bock, S. C. (1995) Biochem. J. 310, 323-330). Relative heparin affinities of basic-to-Ala substitution mutants were determined by NaCl gradient elution from heparin columns. The data show that only a subset of the previously implicated basic residues are critical for binding to heparin. The key heparin binding residues, Lys-11, Arg-13, Arg-24, Arg-47, Lys-125, Arg-129, and Arg-145, line a 50-A long channel on the surface of ATIII. Comparisons of binding residue positions in the structure of P14-inserted ATIII and models of native antithrombin, derived from the structures of native ovalbumin and native antichymotrypsin, suggest that heparin may activate antithrombin by breaking salt bridges that stabilize its native conformation. Specifically, heparin release of intramolecular helix D-sheet B salt bridges may facilitate s123AhDEF movement and generation of an activated species that is conformationally primed for reactive loop uptake by central beta-sheet A and for inhibitory complex formation. In addition to providing a structural explanation for the conformational change observed upon heparin binding to antithrombin III, differences in the affinities of native, heparin-bound, complexed, and cleaved ATIII molecules for heparin can be explained based on the identified binding site and suggest why heparin functions catalytically and is released from antithrombin upon inhibitory complex formation.
Acetylcholinesterase Staining in Human Auditory and Language Cortices: Regional Variation of Structural Features (1996)

Cholinergic innervation of the cerebral neocortex arises from the basal forebrain and projects to all cortical regions. Acetylcholinesterase (AChE), the enzyme responsible for deactivating acetylcholine, is found within both cholinergic axons arising from the basal forebrain and a subgroup of pyramidal cells in layers III and V of the cerebral cortex. This pattern of staining varies with cortical location and may contribute uniquely to cortical microcircuitry within functionally distinct regions. To explore this issue further, we examined the pattern of AChE staining within auditory, auditory association, and putative language regions of whole, postmortem human brains. The density and distribution of acetylcholine-containing axons and pyramidal cells vary systematically as a function of auditory processing level. Within primary auditory regions AChE-containing axons are dense and pyramidal cells are largely absent. Adjacent cortical regions show a decrease in the density of AChE-containing axons and an increase in AChE-containing pyramidal cells. The posterior auditory and language regions contain a relatively high density of AChE-containing pyramidal cells and AChE-containing axons. Although right and left posterior temporal regions are functionally asymmetrical, there is no apparent asymmetry in the general pattern of AChE staining between homologous regions of the two hemispheres. Thus, the pattern of AChE staining covaries with processing level in the hierarchy of auditory cortical regions, but does not vary between the functionally distinct right and left posterior regions. An asymmetry in the size of layer III AChE-rich pyramidal cells was present within a number of cortical regions. Large AChE-rich pyramidal cells of layer III were consistently greater in size in the left hemisphere as compared to the right. Asymmetry in layer III pyramidal cell size was not restricted to language-associated regions, and could potentially have a variety of etiologies including structural, connectional, and activational differences between the left and right hemisphere.
Design of Porphyrin‐dota‐Like Scaffolds as All‐in‐One Multimodal Heterometallic Complexes for Medical Imaging (2013)

Abstract A series of four multimodal ligands incorporating one porphyrin moiety and one or more dota‐like macrocycles all‐in‐one in the same molecular architecture have been synthesized and full characterized. The corresponding gadolinium(III) complexes were also synthesized and heterometallic complexes incorporating both gadolinium(III) and copper(II) ions were prepared as potential MRI/PET multimodal contrast agents. One ligand ( L4 ) includes an amine moiety that can be activated for easy conversion into an isothiocyanate group for further anchoring to a biological vector. Preliminary relaxivity, cytotoxicity, and MRI studies showed that the complexes developed in this work are very promising medical‐imaging agents for the enhancement of contrast in bimodal MRI techniques.
Somatotropic axis and body weight in pre-menopausal and post-menopausal women: evidence for a neuroendocrine derangement, in absence of changes of insulin-like growth factor binding protein concentrations (1998)

The altered function of the somatotropic axis observed in perimenopause may underlie the changes in body weight and fat distribution. The aim of the present study was to evaluate, in pre-menopausal and post-menopausal women with body mass index (BMI) > or = or <25, the basal plasma levels of growth hormone (GH), insulin-like growth factor (IGF)-I and -II, IGF binding protein (IGFBP)-1 and -3, and the response of GH and IGFBP-1 and -3 to GH releasing hormone (GHRH) and GHRH plus arginine tests. GH and IGF-I basal concentrations were significantly higher in pre-menopausal than in post-menopausal women, while IGF-II, IGFBP-1 and IGFBP-3 concentrations did not vary significantly. IGFBP-1, but not IGFBP-3, concentrations were higher in lean than in obese patients. Insulin concentrations were significantly higher in obese patients, while no differences were observed between pre-menopausal and post-menopausal women. In all subjects, GH concentrations increased significantly during GHRH test; pre-menopausal and lean women showed a higher response compared to post-menopausal and obese women. The GHRH plus arginine test stimulated GH response in all women, irrespective of age and BMI. IGFBP-1 and -3 concentrations did not vary in response to GHRH or GHRH plus arginine tests. The somatotropic axis undergoes modifications in post-menopausal women, apparently not involving IGFBP-1 and -3. Arginine infusion restores the response of GH to GHRH, in both post-menopausal and obese subjects. A somatostatinergic hyperactivity at the climateric period may underlie the changes both in body weight and somatotropic axis.
Ionic Mechanisms Underlying Repetitive High-Frequency Burst Firing in Supragranular Cortical Neurons (2000)

Neocortical neurons in awake, behaving animals can generate high-frequency (>300 Hz) bursts of action potentials, either in single bursts or in a repetitive manner. Intracellular recordings of layer II/III pyramidal neurons were obtained from adult ferret visual cortical slices maintained in vitro to investigate the ionic mechanisms by which a subgroup of these cells generates repetitive, high-frequency burst discharges, a pattern referred to as "chattering." The generation of each but the first action potential in a burst was dependent on the critical interplay between the afterhyperpolarizations (AHPs) and afterdepolarizations (ADPs) that followed each action potential. The spike-afterdepolarization and the generation of action potential bursts were dependent on Na(+), but not Ca(2+), currents. Neither blocking of the transmembrane flow of Ca(2+) nor the intracellular chelation of free Ca(2+) with BAPTA inhibited the generation of intrinsic bursts. In contrast, decreasing the extracellular Na(+) concentration or pharmacologically blocking Na(+) currents with tetrodotoxin, QX-314, or phenytoin inhibited bursting before inhibiting action potential generation. Additionally, a subset of layer II/III pyramidal neurons could be induced to switch from repetitive single spiking to a burst-firing mode by constant depolarizing current injection, by raising extracellular K(+) concentrations, or by potentiation of the persistent Na(+) current with the Na(+) channel toxin ATX II. These results indicate that cortical neurons may dynamically regulate their pattern of action potential generation through control of Na(+) and K(+) currents. The generation of high-frequency burst discharges may strongly influence the response of postsynaptic neurons and the operation of local cortical networks.
Ectopic Expression of the Maize Homeobox Genes ZmHox1a or ZmHox1b Causes Pleiotropic Alterations in the Vegetative and Floral Development of Transgenic Tobacco (1996)

, Bettina Klinge, Wolfgang Werr, Ectopic Expression of the Maize Homeobox Genes ZmHox1a or ZmHox1b Causes Pleiotropic Alterations in the Vegetative and Floral Development of Transgenic Tobacco, The Plant Cell, Vol. 8, No. 3 (Mar., 1996), pp. 349-362
Characterization of solanesyl and decaprenyl diphosphate synthases in mice and humans (2005)

The isoprenoid chain of ubiquinone (Q) is determined by trans‐ polyprenyl diphosphate synthase in micro‐organisms and presumably in mammals. Because mice and humans produce Q 9 and Q 10 , they are expected to possess solanesyl and decaprenyl diphosphate synthases as the determining enzyme for a type of ubiquinone. Here we show that murine and human solanesyl and decaprenyl diphosphate synthases are heterotetramers composed of newly characterized hDPS1 (mSPS1) and hDLP1 (mDLP1), which have been identified as orthologs of Schizosaccharomyces pombe Dps1 and Dlp1, respectively. Whereas hDPS1 or mSPS1 can complement the S. pombe dps1 disruptant, neither hDLP1 nor mDLP1 could complement the S. pombe dLp1 disruptant. Thus, only hDPS1 and mSPS1 are functional orthologs of SpDps1. Escherichia coli was engineered to express murine and human SpDps1 and/or SpDlp1 homologs and their ubiquinone types were determined. Whereas transformants expressing a single component produced only Q 8 of E. coli origin, double transformants expressing mSPS1 and mDLP1 or hDPS1 and hDLP1 produced Q 9 or Q 10 , respectively, and an in vitro activity of solanesyl or decaprenyl diphosphate synthase was verified. The complex size of the human and murine long‐chain trans‐ prenyl diphosphate synthases, as estimated by gel‐filtration chromatography, indicates that they consist of heterotetramers. Expression in E. coli of heterologous combinations, namely, mSPS1 and hDLP1 or hDPS1 and mDLP1, generated both Q 9 and Q 10 , indicating both components are involved in determining the ubiquinone side chain. Thus, we identified the components of the enzymes that determine the side chain of ubiquinone in mammals and they resembles the S. pombe , but not plant or Saccharomyces cerevisiae , type of enzyme.
Free-hand sketch grouping for video retrieval (2008)

We present an algorithm for extracting object descriptions from free-hand sketches of remembered scenes, drawn as video retrieval queries. Our sketches depict scene content, as well as indicators of motion. We report an exploratory study investigating how people sketch to depict recalled events. We incorporate several observations from this study into the design of a novel sketch parsing algorithm. We draw upon a temporal HMM classifier to recognise common pictograms, and graph-cut to identify more general objects.
Diagnosis of Militarily Relevant Diseases Using Oral Fluid and Saliva Antibodies: Fluorescence Polarization Immunoassay (2003)

This laboratory is developing fluorescence polarization (FP) methods as diagnostic tools to assay antibodies in saliva and other oral fluids. FP provides quantitation of molecular interaction, such as antigen-antibody binding, of a single, small-volume sample in real time and without prior separation of components such as blood cells. There is potential for wide-spread use of these homogeneous assays as noninvasive tests, especially as more compact, simplified fluorescence polarimeters become available. FP tests can be designed that are applicable to a wide spectrum of microorganisms and may be used in a clinic or far-forward deployed setting to aid in diagnosis of disease or verification of vaccination. Rapid salivary diagnostics, including FP, have been identified by the Office of Naval Research as requirements for future naval capabilities in basic and applied medical research for warfighter protection in casualty prevention. The applications of FP salivary diagnostics for determination of tuberculosis exposure and of anthrax immunization status are discussed as examples.
Surface-dependent reactions of the vitamin K-dependent enzyme complexes (1990)

During the past 20 years contributions from many laboratories have led to the development of isolation procedures, delineation of primary structures, and more recently, to the expression of recombinant proteins associated with the coagulation cascade. In general, studies of coagulation proteins under defined conditions have demonstrated the prescience of Davie and Ratnoff and MacFarlane in their proposals of the coagulation cascade. The more recent discovery of thrombomodulin by Esmon et al has led to the identification and characterization of components of the vitamin K-dependent anticoagulant pathway. In this review we have attempted to analyze and compare the functional properties of each of the vitamin K-dependent enzyme complexes associated with the procoagulant and anticoagulant phases of blood clotting. Although dissimilarities exist, the vitamin K-dependent complexes have analogous requirements and appear to function with a common general mode of organization. Membrane-bound cofactors serve as anchoring sites for the appropriate membrane-binding enzymes. This process localizes the complex on the membrane surface and increases the catalytic efficiency for substrate utilization. Complex formation provides extraordinary improvements in the catalytic efficiency for the complexes as compared with their soluble enzyme components. Membrane- bound complexes provide a mechanism that can be regulated at a site by membrane presentation, zymogen activation, and cofactor activation or presentation. The kinetic constants obtained for the various coagulation reactions determined in vitro provide some insights into how these pathways may function in vivo. The catalytic efficiency (kcat/Km) for factor X activation by factor VIIIa/factor IXa is far in excess of the catalytic efficiency of activation of factor X by tissue factor/factor VIIa (Table 3). This may provide a rational interpretation for the observation that patients with hemophilia A and B bleed even though they appear to have an alternative pathway to factor X activation. In addition, tissue factor is not ordinarily presented by the vascular tissue that has direct access to blood. However, it appears that extravascular constitutive tissue factor is available once the blood vessel becomes disrupted. The efforts to identify the initiating reactions of the blood coagulation process have not been unambiguously successful. We conclude that factor VII is most likely a zymogen, just as are the other proenzymes of the blood clotting process. In addition, it is difficult to rationalize the importance of the intrinsic pathway of coagulation involving factor XII, prekallikrein, and high molecular weight kininogen since the congenital absence of any one of these factors does not result in abnormal bleeding.
Effect of Cheese, With and Without Sucrose, on Dental Caries and Recovery of Streptococcus mutans in Rats (1984)

The objective of this study was to determine the effect of aged and young cheddar cheese with and without added sucrose on dental caries and the associated recovery of implanted Streptococcus mutans. Very little caries was observed in rats consuming cheese without sucrose. There was an increase in caries in rats fed cheeses with 20% sucrose, but this increase was not significant. There was significantly greater caries activity in rats fed standard diets containing 20% or 5% sucrose (SLS or MIT 305) than in rats fed cheeses containing 20% sucrose. Rats fed cheese or powdered diets containing sucrose had significantly higher frequency of recovery and higher levels of S. mutans infection than did rats fed cheese containing no sucrose. This study confirms the low cariogenic potential and possible cariostatic activity of cheddar cheese in rats. Since cheddar cheese with sucrose did not significantly interfere with S. mutans implantation, the cariostatic mechanism is apparently unrelated to a direct antimicrobial effect on S. mutans.
All-Frequency Precomputed Radiance Transfer for Glossy Objects (2004)

We introduce a method based on precomputed radiance transfer (PRT) that allows interactive rendering of glossy surfaces and includes shadowing effects from dynamic, "all-frequency" lighting. Specifically, source lighting is represented by a cube map at resolution nL
Design, synthesis, and evaluation of DNA minor groove binding agents: the duocarmycins (1994)

Abstract