gebhart/patrepeval huggingface dataset:
Therapeutic potential of positive AMPA receptor modulators in the treatment of neurological disease (2000)

Excitatory neurotransmission in the CNS depends heavily upon alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-type glutamate receptors. Derangements in AMPA receptor mediated synaptic transmission may be a contributing factor in neurological and neurodegenerative diseases and could be a target for therapeutic intervention. Recently, drugs that positively modulate AMPA receptors have been identified, having differential effects upon certain AMPA receptor subunits and different effects upon physiological properties of AMPA receptors. These drugs facilitate AMPA receptor mediated processes and may have beneficial therapeutic effects. For example, certain AMPA modulators facilitate long-term potentiation, which is considered a cellular mechanism that may be important for memory storage and they also facilitate memory encoding in behavioural experiments. Thus, AMPA modulators might ameliorate memory deficits that occur in dementia, such as Alzheimer's disease (AD). However, AMPA receptor mediated excitotoxicity may occur with excessive AMPA receptor activation which occurs in seizures or ischaemia and positive AMPA modulators could promote neuronal injury in those conditions. Ultimately, the clinical utility of positive AMPA modulators will be dependent upon understanding the role of AMPA receptors in certain neurological disorders, identifying receptor subtypes involved in specific neurological disorders and developing drugs with selective actions upon specific AMPA receptor properties that also possess receptor subtype specificity. Currently available drugs have provided significant insight into the physiology and structural determinants of important AMPA receptor properties and some insight into potential clinical uses as well as potential dangers of such drugs.
The sesquiterpene lactone dehydroleucodine reversibly inhibits Allium cepa L. root growth. (2001)

Here, we prove that dehydroleucodine, a sesquiterpene lactone, at low concentrations (25-100 microM) slowed down the Allium cepa L root growth by 22-70% respectively neither affecting cell viability nor cell size. Removal of the drug after 24 h incubation restored the normal growth rate of the roots. Higher concentrations (200 microM) of dehydroleucodine were deleterious for the roots. As cell size did not change, it is most likely that dehydroleucodine affected some event of cell division cycle making it longer. Thus, dehydroleucodine could be a useful tool to slow down cell proliferation.
Oligosaccharide sequences in <i>Quillaja</i> saponins by electrospray ionization ion trap multiple‐stage mass spectrometry (2004)

Ten different samples with 13 previously identified saponin structures from Quillaja saponaria Molina were investigated by electrospray ionization ion trap multiple-stage mass spectrometry (ESI-ITMS(n)) in positive and negative ion modes. Both positive and negative ion mode MS(1)-MS(4) spectra were analyzed, showing that structural information on the two oligosaccharide parts in the saponin can be obtained from positive ion mode spectra whereas negative ion mode spectra mainly gave information on one of the oligosaccharide parts. Analysis of MS(1)-MS(4) spectra identified useful key fragment ions important for the structural elucidation of Quillaja saponins. A flowchart involving a stepwise procedure based on key fragments from MS(1)-MS(3) spectra was constructed for the identification of structural elements in the saponin. Peak intensity ratios in MS(3) spectra were found to be correlated with structural features of the investigated saponins and are therefore of value for the identification of terminal monosaccharide residues.
Epidermal growth factor replaces estrogen in the stimulation of female genital-tract growth and differentiation. (1991)

The in vivo studies presented here demonstrate that epidermal growth factor (EGF) is an important autocrine and/or paracrine mediator of estrogen-induced growth and differentiation in mouse uterus and vagina. An antibody specific for EGF significantly inhibited estrogen-induced uterine and vaginal growth, thereby implicating EGF involvement in estrogen action. Furthermore, EGF administered via slow-release pellets in ovariectomized mice acted as a potent uterine and vaginal mitogen as well as an inducer of vaginal keratinization. Experiments with ovariectomized, adrenalectomized, hypophysectomized mice indicated that EGF mitogenesis does not require pituitary or adrenal hormones. Treatment with EGF also mimicked estrogen in the induction of uterine lactoferrin (a major estrogen-inducible secretory protein) mRNA and protein. These data suggest that EGF has estrogen-like effects in the promotion of cell growth in the reproductive tract and that EGF may serve as an important mediator of estrogen action in vivo.
Neutralization of Autocrine Transforming Growth Factor‐β in Human Cord Blood CD34<sup>+</sup>CD38<sup>−</sup>Lin<sup>−</sup>Cells Promotes Stem‐Cell‐Factor‐Mediated Erythropoietin‐Independent Early Erythroid Progenitor Development and Reduces Terminal Differentiation (2003)

Transforming growth factor (TGF)-beta1 exerts autocrine and paracrine effects on hematopoiesis. Here, we have attempted to evaluate the effect of endogenous TGF-beta1 on early erythroid development from primitive human hematopoietic stem cells (HSCs) and to assess the effects of TGF-beta1 on different phases of erythropoiesis. Cord blood CD34(+)CD38(-) lineage-marker-negative (Lin(-)) cells were cultured in serum-free conditions using various combinations of stem cell factor (SCF), erythropoietin (Epo), and TGF-beta-neutralizing antibody. Generation of erythroid progenitors was assessed using colony assay and flow cytometry. Terminal erythroid differentiation was examined when SCF/Epo-stimulated cells were recultured in the presence of Epo with and without TGF-beta1. Anti-TGF-beta augmented the proliferation of CD34(+)CD38(-)Lin(-) cells (day 21) in SCF-stimulated (6.4-fold +/- 1.5-fold) and SCF/Epo-stimulated (2.9-fold +/- 1.2-fold) cultures. Cells stimulated by SCF/Epo underwent similar levels of erythroid differentiation with and without anti-TGF-beta. While SCF alone stimulated the production of tryptase-positive mast cells, cells stimulated by SCF/anti-TGF-beta were predominantly erythroid (CD36(+)CD14(-) and glycophorin A positive). A distinct expansion of erythroid progenitors (CD34(+)CD36(+)CD14(-)) with the potential to form erythroid colonies was seen, revealing early Epo-independent erythroid development. In contrast, the kinetics of erythroid progenitor generation from primitive HSCs indicate that TGF-beta1 is not inhibitory in late erythropoiesis, but it accelerated the conversion of large BFU-E into colony-forming units-erythroid. Finally, TGF-beta1 accelerated Epo-induced terminal erythroid differentiation and resulted in a greater level of enucleation (22% +/- 6% versus 7% +/- 3%) in serum-free conditions. Serum addition stimulated enucleation (54% +/- 18%), which was lower (26% +/- 14%) with anti-TGF-beta, suggesting that optimal erythroid enucleation is Epo dependent, requiring serum factors including TGF-beta1.
An escape routing framework for dense boards with high-speed design constraints (2005)

Shrinking transistor sizes, increasing circuit complexities, and high clock frequencies bring new board routing challenges that cannot be handled effectively by traditional routing algorithms. Many high-end designs in the industry today require manual routing efforts, which increases the design cycle times considerably. In this paper, we propose an escape routing algorithm to route nets within multiple dense components simultaneously so that the number of crossings in the intermediate area is minimized. We also show how to handle high-speed design constraints within the framework of this algorithm. Experimental comparisons with a recently proposed algorithm (Ozdal and Wong, 2004) show that our algorithm reduces the via requirements of industrial test cases on average by 39%.
Tacrolimus for the treatment of systemic lupus erythematosus with pure class V nephritis (2008)

A 6-month course of tacrolimus is a safe and effective treatment of pure class V (membranous) lupus nephritis. As compared with conventional cytotoxic treatment, tacrolimus possibly results in a faster resolution of proteinuria, and a lower risk of lupus flare within 1 yr. The long-term effect and optimal regimen of tacrolimus require further study.
Radio software download for commercial wireless reconfigurable devices (2004)

Commercial wireless end user terminals are becoming increasingly complex in order to integrate in a common package distinct separate capabilities formerly implemented in multiple single-function, single-band devices. Software is an increasingly important aspect of these complex terminals. The increased amount of software installed in wireless devices includes both application software and operational software, such as radio software used to implement software-defined radio capabilities. A resulting need is to be able to upgrade these wireless devices through software download in order to incorporate new capabilities and fix software deficiencies.
Systematic review with meta‐analysis: efficacy and safety of oral Janus kinase inhibitors for inflammatory bowel disease (2019)

JAK inhibitors are effective for inducing clinical remission in CD and induction of clinical and endoscopic remission in UC, although are associated with an increased risk of infectious complications.
The selective muscarinic agonist xanomeline improves both the cognitive deficits and behavioral symptoms of Alzheimer disease. (1997)

The therapeutic effects of selective cholinergic replacement using oral xanomeline, an m1/m4 receptor agonist, were assessed in a multicenter study of 343 patients with Alzheimer disease (AD). Patients were randomized to parallel treatment arms (placebo, 25, 50, and 75 mg t.i.d. xanomeline) and followed through 6 months of double-blind therapy and 1 month of single-blind placebo washout. Completer analysis, using the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog), revealed a significant treatment effect (75 mg t.i.d. vs. placebo; p = 0.045). Similar assessment of global status, using the Clinician's Interview-Based Impression of Change, was also significant (75 mg t.i.d. vs. placebo; p = 0.022). Treatment Emergent Signs and Symptoms analysis of the Alzheimer's Disease Symptomatology Scale, revealed highly significant (p < or = 0.002) dose-dependent reductions in vocal outbursts, suspiciousness, delusions, agitation, and hallucinations. On end-point analysis, the Nurses' Observational Scale for Geriatric Patients also showed a significant dose-response relationship (p = 0.018). The improvement in ADAS-Cog provides the first clinical evidence of involvement of the m1 muscarinic receptor in cognition. Furthermore, the favorable effects of xanomeline on disturbing behaviors suggest a novel approach for treatment of the noncognitive symptoms of AD. Although adverse effects (mainly gastrointestinal) associated with the oral formulation appear to limit its use, a large-scale study investigating the safety and efficacy of transdermal xanomeline is under way.
Antibody-drug conjugates: Intellectual property considerations (2015)

Antibody-drug conjugates are highly complex entities that combine an antibody, a linker and a toxin. This complexity makes them demanding both technically and from a regulatory point of view, and difficult to deal with in their patent aspects. This article discusses different issues of patent protection and freedom to operate with regard to this promising new class of drugs.
Topographic Microscope (1958)

Microscopic topography of matte and mirror surfaces can be measured visually. A straight-line reticle perpendicular to the plane of incidence is optically projected obliquely onto the surface. The image deviates laterally in response to vertical surface deviation. A microscope equipped with a filar eyepiece is used to measure the image deviation from a straight line. A simple formula based on the geometry of the optics is used to calculate the topographic deviation. Precision on surface grooves of 0.0005–0.005 in. deep is about ±6%. Sensitivity is around 0.00003 in. The method is absolute, quick, easy, and usable on nonflat surfaces.
The Origin of Stress in Metal Layers Condensed from the Vapour in High Vacuum (1953)

Measurements are made of the stress in deposits of Ni, Fe, Pd, Au, Cu, Ag, Sb, Al, Bi, Mg and Zn condensed from the vapour in high vacuum on copper strips used as substrates. The stress is found to be characteristically of a tensile nature and the amount of stress is different for different metals.
Presentation and validation of the Radboud Faces Database (2010)

Many research fields concerned with the processing of information contained in human faces would benefit from face stimulus sets in which specific facial characteristics are systematically varied while other important picture characteristics are kept constant. Specifically, a face database in which displayed expressions, gaze direction, and head orientation are parametrically varied in a complete factorial design would be highly useful in many research domains. Furthermore, these stimuli should be standardised in several important, technical aspects. The present article presents the freely available Radboud Faces Database offering such a stimulus set, containing both Caucasian adult and children images. This face database is described both procedurally and in terms of content, and a validation study concerning its most important characteristics is presented. In the validation study, all frontal images were rated with respect to the shown facial expression, intensity of expression, clarity of expression, genuineness of expression, attractiveness, and valence. The results show very high recognition of the intended facial expressions.
A high-precision time-to-digital converter using a two-level conversion scheme (2004)

This paper describes a design of time-to-digital converter (TDC) using a two-level conversion scheme. The first level is accomplished by a multi-phase sampling technique with the aid of delay-locked loop (DLL). Then the input signal and its adjacent sampling clock are manipulated and sent into a vernier delay line (VDL) sampling circuit at the second level. The proposed TDC can provide high resolution with less hardware compared to one level VDL sampling circuit with the same dynamic range. A new architecture of dual DLL circuit is also implemented to stabilize delay control against process and ambient variations. A test chip is designed and fabricated in 0.35-/spl mu/m logic technology. With an input reference clock within 130 to 160 MHz, the TDC achieves 24 to 30 ps resolution. The DNL is less than /spl plusmn/0.55 LSB and INL is within +1 to -1.5 LSB.
Human Dendritic Cells Derived From Embryonic Stem Cells Stably Modified With CD1d Efficiently Stimulate Antitumor Invariant Natural Killer T Cell Response (2013)

Abstract Invariant natural killer T (iNKT) cells are a unique lymphocyte subpopulation that mediates antitumor activities upon activation. A current strategy to harness iNKT cells for cancer treatment is endogenous iNKT cell activation using patient-derived dendritic cells (DCs). However, the limited number and functional defects of patient DCs are still the major challenges for this therapeutic approach. In this study, we investigated whether human embryonic stem cells (hESCs) with an ectopically expressed CD1d gene could be exploited to address this issue. Using a lentivector carrying an optimized expression cassette, we generated stably modified hESC lines that consistently overexpressed CD1d. These modified hESC lines were able to differentiate into DCs as efficiently as the parental line. Most importantly, more than 50% of such derived DCs were CD1d+. These CD1d-overexpressing DCs were more efficient in inducing iNKT cell response than those without modification, and their ability was comparable to that of DCs generated from monocytes of healthy donors. The iNKT cells expanded by the CD1d-overexpressing DCs were functional, as demonstrated by their ability to lyse iNKT cell-sensitive glioma cells. Therefore, hESCs stably modified with the CD1d gene may serve as a convenient, unlimited, and competent DC source for iNKT cell-based cancer immunotherapy.
Position-sensorless control of permanent magnet synchronous machines over wide speed range (2007)

Permanent-magnet-synchronous-machine (PMSM) drives have been increasingly applied in a variety of industrial applications which require fast dynamic response and accurate control over wide speed ranges.However, there still exist challenges to design position-sensorless vector control of PMSM operating in a wide speed range, which covers both constant-torque and constant-power region.Thus, two control techniques are proposed in this dissertation for PMSM drives, namely flux-weakening control incorporating speed regulation and sliding mode observer with feedback of equivalent control.The research objectives are to extend the operating speed range of the PMSM drive system and improve its control robustness and adaptability to variations of operating conditions as well as dynamic performance.I wish to express my deep gratitude to my adviser, Professor Longya Xu, for his
Molecular regulation of cognitive functions and developmental plasticity: impact of GABA<sub>A</sub>receptors (2007)

By controlling spike timing and sculpting neuronal rhythms, inhibitory interneurons play a key role in regulating neuronal circuits and behavior. The pronounced diversity of GABAergic (gamma-aminobutyric acid) interneurons is paralleled by an extensive diversity of GABAA receptor subtypes. The region- and domain-specific location of these receptor subtypes offers the opportunity to gain functional insights into the role of defined neuronal circuits. These developments are reviewed with regard to the regulation of sleep, anxiety, memory, sensorimotor processing and post-natal developmental plasticity.
Analysis of S-Acylation of Proteins (2008)

Palmitoylation or S-acylation is the post-translational attachment of fatty acids to cysteine residues and is common among integral and peripheral mem brane proteins. Palmitoylated proteins have been found in every eukaryotic cell type examined (yeast, insect, and vertebrate cells), as well as in viruses grown in these cells. The exact functions of protein palmitoylation are not well understood. Intrin sically hydrophilic proteins, especially signaling molecules, are anchored by long chain fatty acids to the cytoplasmic face of the plasma membrane. Palmitoylation may also promote targeting to membrane subdomains enriched in glycosphingolip ids and cholesterol or affect protein-protein interactions. This chapter describes (1) a standard protocol for metabolic labeling of palmitoylated proteins and also the procedures to prove a covalent and ester-type linkage of the fatty acids, (2) a simple method to analyze the fatty acid content of S-acylated proteins, (3) two methods to analyze dynamic palmitoylation for a given protein and (4) protocolls to study cell-free palmitoylation of proteins.
Terahertz Time-Domain Spectroscopy for Material Characterization (2007)

Terahertz time-domain spectroscopy is used to study properties of nonpolar amorphous materials. Terahertz absorption spectra and refractive indices were measured in a number of glasses, lubricating oils, and polymers, and the results were correlated with material properties.
A murine model of myocardial microvascular thrombosis (1999)

Disorders of hemostasis lead to vascular pathology. Endothelium-derived gene products play a critical role in the formation and degradation of fibrin. We sought to characterize the importance of these locally produced factors in the formation of fibrin in the cardiac macrovasculature and microvasculature. This study used mice with modifications of the thrombomodulin (TM) gene, the tissue-type plasminogen activator (tPA) gene, and the urokinase-type plasminogen activator (uPA) gene. The results revealed that tPA played the most important role in local regulation of fibrin deposition in the heart, with lesser contributions by TM and uPA (least significant). Moreover, a synergistic relationship in fibrin formation existed in mice with concomitant modifications of tPA and TM, resulting in myocardial necrosis and depressed cardiac function. The data were fit to a statistical model that may offer a foundation for examination of hemostasis-regulating gene interactions.
Architecture of the Outer Membrane of <i>Escherichia coli</i> III. Protein-Lipopolysaccharide Complexes in Intramembraneous Particles (1978)

In a previous paper (A. Verkleij, L. van Alphen, J. Bijvelt, and B. Lugtenberg, Biochim. Biophys. Acta 466:269-282, 1977) we have hypothesized that particles on the outer fracture face of the outer membrane ([Formula: see text]), with corresponding pits on the inner fracture face of the outer membrane ([Formula: see text]), consist of lipopolysaccharide (LPS) aggregates stabilized by divalent cations and that they might contain protein and/or phospholipid. In the present paper the roles of LPS, cations, and proteins in these [Formula: see text] particles are described more extensively, using a strain that lacks the major outer membrane proteins, b, c, and d (b(-) c(-) d(-)), and has a reduction in the number of [Formula: see text] particles of 75%. To study the role of divalent cations in the formation of [Formula: see text] particles, these b(-) c(-) d(-) cells were grown or incubated with Ca(2+), Mg(2+), or putrescine. The presence of Ca(2+) resulted in the appearance of many [Formula: see text] particles and [Formula: see text] pits. Mg(2+) and putrescine were less effective than Ca(2+). Introduction of these particles was not accompanied by alterations in the relative amounts of LPS and cell envelope proteins. Ca(2+) treatment of a heptoseless derivative of a b(-) c(-) d(-) strain did not result in morphological changes. Incubation of Ca(2+)-treated cells with ethylenediaminetetraacetate caused the disappearance of the introduced particles as well as the release of more than 60% of the cellular LPS. These results strongly support the hypothesis that LPS is involved in the formation of [Formula: see text] particles and [Formula: see text] pits. The roles of various outer membrane proteins in the formation of [Formula: see text] particles were studied by comparing the freeze-fracture morphology of b(-) c(-) d(-) cells with that of cells which contain one of the outer membrane proteins b, c, d, and e or the receptor protein for bacteriophage lambda. The results showed that the presence of any of these five proteins in a b(-) c(-) d(-) background resulted in a large increase in the number of [Formula: see text] particles and [Formula: see text] pits, indicating that these proteins are, independent of each other, involved in the formation of [Formula: see text] particles and [Formula: see text] pits. The simplest explanation for the results is that in wild-type cells each particle consists of LPS complexed with some molecules of a single protein species, stabilized by either divalent cations or polyamines. It is hypothesized that the outer membrane of the wild-type cell contains a heterogeneous population of particles, of which 75% consists of protein b-LPS, protein c-LPS, and protein d-LPS particles. A function of these particles as aqueous pores is proposed.