gebhart/patrepeval huggingface dataset:
Convulsive seizures and SUDEP in a mouse model of SCN8A epileptic encephalopathy (2014)

De novo mutations of the voltage-gated sodium channel gene SCN8A have recently been recognized as a cause of epileptic encephalopathy, which is characterized by refractory seizures with developmental delay and cognitive disability. We previously described the heterozygous SCN8A missense mutation p.Asn1768Asp in a child with epileptic encephalopathy that included seizures, ataxia, and sudden unexpected death in epilepsy (SUDEP). The mutation results in increased persistent sodium current and hyperactivity of transfected neurons. We have characterized a knock-in mouse model expressing this dominant gain-of-function mutation to investigate the pathology of the altered channel in vivo. The mutant channel protein is stable in vivo. Heterozygous Scn8a(N1768D/+) mice exhibit seizures and SUDEP, confirming the causality of the de novo mutation in the proband. Using video/EEG analysis, we detect ictal discharges that coincide with convulsive seizures and myoclonic jerks. Prior to seizure onset, heterozygous mutants are not defective in motor learning or fear conditioning, but do exhibit mild impairment of motor coordination and social discrimination. Homozygous mutant mice exhibit earlier seizure onset than heterozygotes and more rapid progression to death. Analysis of the intermediate phenotype of functionally hemizygous Scn8a(N1768D/-) mice indicates that severity is increased by a double dose of mutant protein and reduced by the presence of wild-type protein. Scn8a(N1768D) mutant mice provide a model of epileptic encephalopathy that will be valuable for studying the in vivo effects of hyperactive Nav1.6 and the response to therapeutic interventions.
<title>Event-averaged maximum likelihood estimation and information-based sensor management</title> (1994)

This paper present an information-theoretic approach to sensor management for multitarget tracking using a sensor that operates in one of two modes: a fast, low-resolution mode and a slow, high-resolution mode. The error correlations between nearby target pairs, the sensor rates, the sensor resolutions and the target plant noise all play a role in the optimum choice of mode. The error correlations occur in the target location estimates even when the individual measurement errors are uncorrelated, as in the model considered here. When a filter that models these error correlations is used, such as event-averaged maximum likelihood estimation, a sensor management strategy can be developed to reduce them. This is illustrated with a model two- target problem. In the model problem, the target plant noise is such that the low resolution mode produces the optimum result when the targets are widely separated, due to its higher report rate. If the error correlations are not modeled, then over a certain parameter range the low resolution mode would be selected for all target separations. When the effect of error correlations is included, it is shown the slow, high resolution mode produces a better result when the targets are close together. This suggests that systems that must track closely spaced targets could benefit from adaptively adjusting their integration times based on target plant noise and separation.
Role of TraT protein, an anticomplementary protein produced in Escherichia coli by R100 factor, in serum resistance (1992)

Escherichia coli K12 strain W3110/SM bearing a plasmid containing the traT gene (traT+ strain) was more resistant to the bactericidal activity of guinea pig serum than the same strain bearing this plasmid without the traT gene (traT- strain). A murine mAb was generated against synthetic TraT peptide (86-99). This antibody reacted only with denatured TraT protein, but it was used for monitoring TraT protein by immunoblotting during purification of the protein. Six mAb were then generated against partially purified traT protein from the solubilized membrane fraction of the traT+ strain. These mAb reacted with the native protein even on living cells, and their F(ab) fragments were found to suppress the inhibitory effect of the TraT protein on the bactericidal activity of serum. TraT protein was purified from solubilized membranes of the traT+ strain by ion exchange and gel filtration chromatographies. The purified TraT protein inhibited the lysis of sensitized erythrocytes by serum complement. Its inhibitory action was mainly on the C6 step. It strongly inhibited the reaction of C6 with EAC14b2a3b and excess C5, C7, C8, and C9. TraT protein also inhibited the reaction of C7-deficient human serum with guinea pig erythrocytes when it was activated by cobra venom factor. It did not inhibit the reaction of preformed C5b6 complexes. However, TraT did not have any effect on the cleavage of 125I[C5] to 125I[C5b] in similar conditions. It also partially inhibited the reaction steps of C4, C5, and factor B and limited guinea pig complement serum in 0.1% gelatin veronal buffered saline, pH 7.4, containing 10 mM EDTA with their respective preceding intermediate cells. It had no effect on either the binding of C3 to EAC14b2a or the cleavage of C3b by factors H and I. TraT protein probably inhibits the formation of C5b6 complex or causes structural alteration of the complex to a nonfunctional form.
IL-6/IL-6 receptor system and its role in physiological and pathological conditions (2011)

IL (interleukin)-6, which was originally identified as a B-cell differentiation factor, is a multifunctional cytokine that regulates the immune response, haemopoiesis, the acute phase response and inflammation. IL-6 is produced by various types of cell and influences various cell types, and has multiple biological activities through its unique receptor system. IL-6 exerts its biological activities through two molecules: IL-6R (IL-6 receptor) and gp130. When IL-6 binds to mIL-6R (membrane-bound form of IL-6R), homodimerization of gp130 is induced and a high-affinity functional receptor complex of IL-6, IL-6R and gp130 is formed. Interestingly, sIL-6R (soluble form of IL-6R) also binds with IL-6, and the IL-6-sIL-6R complex can then form a complex with gp130. The homodimerization of receptor complex activates JAKs (Janus kinases) that then phosphorylate tyrosine residues in the cytoplasmic domain of gp130. The gp130-mediated JAK activation by IL-6 triggers two main signalling pathways: the gp130 Tyr759-derived SHP-2 (Src homology 2 domain-containing protein tyrosine phosphatase-2)/ERK (extracellular-signal-regulated kinase) MAPK (mitogen-activated protein kinase) pathway and the gp130 YXXQ-mediated JAK/STAT (signal transducer and activator of transcription) pathway. Increased IL-6 levels are observed in several human inflammatory diseases, such as rheumatoid arthritis, Castleman's disease and systemic juvenile idiopathic arthritis. IL-6 is also critically involved in experimentally induced autoimmune diseases. All clinical findings and animal models suggest that IL-6 plays a number of critical roles in the pathogenesis of autoimmune diseases. In the present review, we first summarize the IL-6/IL-6R system and IL-6 signal transduction, and then go on to discuss the physiological and pathological roles of IL-6.
L-764406 Is a Partial Agonist of Human Peroxisome Proliferator-activated Receptor γ (1999)

Insulin-sensitizing thiazolidinedione (TZD) compounds are high affinity ligands for a member of the nuclear receptor family, peroxisome proliferator-activated receptor (PPAR) gamma. A scintillation proximity assay for measurement of 3H-radiolabeled TZD binding to human PPARgamma under homogeneous conditions was developed. Using this approach, a novel non-TZD compound (L-764406) was shown to be a potent (apparent binding IC50 of 70 nM) PPARgamma ligand. Preincubation of PPARgamma with L-764406 prevented binding of the [3H]TZD, suggesting a covalent interaction with the receptor; in addition, structurally related analogues of L-764406, which would be predicted not to interact with PPARgamma in a covalent fashion, did not displace [3H]TZD binding to PPARgamma. Covalent binding of L-764406 was proven by an observed molecular weight shift of a tryptic PPARgamma ligand binding domain (LBD) peptide by mass spectrometric analysis. A specific cysteine residue (Cys313 in helix 3 of hPPARgamma2) was identified as the attachment site for this compound. In protease protection experiments, the liganded receptor adopted a typical agonist conformation. L-764406 exhibited partial agonist activity in cells expressing a chimeric receptor containing the PPARgamma LBD and a cognate reporter gene and also induced the expression of the adipocyte-specific gene aP2 in 3T3-L1 cells. In contrast, L-764406 did not exhibit activity in cells transfected with chimeric receptors containing PPARalpha or PPARdelta LBDs. The partial agonist properties of L-764406 were also evident in a co-activator association assay, indicating that the increased transcription in cells was co-activator mediated. Thus, L-764406 is a novel non-TZD ligand for PPARgamma and is also the first known partial agonist for this receptor. The results suggest a critical functional role for Cys313, and helix 3, in contributing to ligand binding and subsequent agonist-induced conformational changes.
Evidence for a mediator cycle at the initiation of transcription (1997)

Free and elongating (DNA-bound) forms of RNA polymerase II were separated from yeast. Most cellular polymerase II was found in the elongating fraction, which contained all enzyme phosphorylated on the C-terminal domain and none of the 15-subunit mediator of transcriptional regulation. These and other findings suggest that mediator enters and leaves initiation complexes during every round of transcription, in a process that may be coupled to C-terminal domain phosphorylation.
Tubular Repair of the Median or Ulnar Nerve in the Human Forearm: A 5-Year Follow-Up (2004)

The long-term outcome from silicone tube nerve repair was compared with the outcome from routine microsurgical repair in a clinical randomized prospective study, comprising 30 patients with median or ulnar nerve injuries in the distal forearm. Postoperatively, the patients underwent neurophysiological and clinical assessments of sensory and motor function regularly over a 5-year period. After 5 years there was no significant difference in outcome between the two techniques except that cold intolerance was significantly less severe with the tubular technique. In the total group there was ongoing improvement of functional sensibility throughout the 5 years after repair. It is concluded that tubular repair of the median and ulnar nerves is at least as good as routine microsurgical repair, and results in less cold intolerance.
Toward a compelling sensation of telepresence: demonstrating a portal to a distant (static) office (2000)

In 1998 we introduced the idea for a project we call the Office of the Future. Our long-term vision is to provide a better every-day working environment, with high-fidelity scene reconstruction for life-sized 3D tele-collaboration. In particular, we want a true sense of presence with our remote collaborator and their real surroundings. The challenges related to this vision are enormous and involve many technical tradeoffs. This is true in particular for scene reconstruction. Researchers have been striving to achieve real-time approaches, and while they have made respectable progress, the limitations of conventional technologies relegate them to relatively low resolution in a restricted volume. We present a significant step toward our ultimate goal, via a slightly different path. In lieu of low-fidelity dynamic scene modeling we present an exceedingly high fidelity reconstruction of a real but static office. By assembling the best of available hardware and software technologies in static scene acquisition, modeling algorithms, rendering, tracking and stereo projective display, we are able to demonstrate a portal to a real office, occupied today by a mannequin, and in the future by a real remote collaborator. We now have both a compelling sense of just how good it could be, and a framework into which we will later incorporate dynamic scene modeling, as we continue to head toward our ultimate goal of 3D collaborative telepresence.
Polymerizable Lyotropic Liquid Crystals Containing Transition-Metal and Lanthanide Ions:  Architectural Control and Introduction of New Properties into Nanostructured Polymers (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTPolymerizable Lyotropic Liquid Crystals Containing Transition-Metal and Lanthanide Ions: Architectural Control and Introduction of New Properties into Nanostructured PolymersHai Deng, Douglas L. Gin, and Ryan C. SmithView Author Information Department of Chemistry, University of California Berkeley, California 94720-1460 Cite this: J. Am. Chem. Soc. 1998, 120, 14, 3522–3523Publication Date (Web):March 28, 1998Publication History Received29 December 1997Published online28 March 1998Published inissue 1 April 1998https://pubs.acs.org/doi/10.1021/ja9743654https://doi.org/10.1021/ja9743654rapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views931Altmetric-Citations75LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Amphiphiles,Ions,Lanthanides,Metals,Nanocomposites Get e-Alerts
An introduction to ordinary differential equations (2004)

This chapter is about the most basic concepts of the theory of differential equations. We will answer some fundamental questions: What is a differential equation? Do differential equations always have solutions? Are solutions of differential equations unique? However, the most important goal of this chapter is to introduce a geometric interpretation for the space of solutions of a differential equation. Using this geometry, we will introduce some of the elements of the subject: rest points, periodic orbits, and invariant manifolds. Finally, we will review the calculus in a Banach space setting and use it to prove the classic theorems on the existence, uniqueness, and extensibility of solutions. References for this chapter include [8], [11], [49], [51], [78], [83], [95], [107], [141], [164], and [179].KeywordsBanach SpacePeriodic SolutionPeriodic OrbitHamiltonian SystemPhase PortraitThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Establishment of Conditionally Immortalized Mouse Glomerular Parietal Epithelial Cells in Culture (2008)

Parietal epithelial cells (PEC) are major constituents of crescents in crescentic glomerulonephritis. The purpose of these studies was to establish an immortalized PEC cell line with similar characteristics to PEC in vivo for use in future mechanistic studies. Glomeruli were isolated from H-2Kb tsA58 transgenic mice (ImmortoMouse) by standard differential sieving, and several candidate PEC cell lines were obtained by subcloning outgrowths of cells from capsulated glomeruli. One clone, designated mouse PEC (mPEC), was extensively characterized. mPEC exhibited a compact cell body with typical epithelial morphology when grown in permissive conditions, but the cell shape changed to polygonal after 14 d in growth-restrictive conditions. mPEC but not podocytes used as a negative control expressed claudin-1, claudin-2, and protein gene product 9.5, which are proteins specific to PEC in vivo, and did not express the podocyte-specific proteins synaptopodin and nephrin. The junctional proteins zonula occludens-1 and beta-catenin stained positively in both mPEC and podocytes, but the staining pattern at cell-cell contacts was intermittent in mPEC and linear in podocytes. Finally, mPEC had thin bundled cortical F-actin filaments and no F-actin projections compared with podocytes, which exhibited thick bundled cortical F-actin filaments and interdigitating F-actin projections at cell-cell contacts. We conclude that immortalized mPEC in culture exhibit specific features of PEC in vivo and that these cells are distinct from podocytes, despite having the same mesenchymal origin. This mPEC line will assist in future mechanistic studies of PEC and enhance our understanding of glomerular injury.
Biochemical Characterisation of A Pancreatic Elastase Inhibitor from the LeechHirudin Aria Manillensis (1993)

The jawed leech, Hirudinaria manillensis is closely related to Hirudo medicinalis, both belonging to the same family Arhynchobdellida. From Hirudo, two potent peptide inhibitors, hirudin (a thrombin inhibitor) and eglin (an elastase/chymotrypsin inhibitor) have been characterised in detail. During our studies to isolate thrombin inhibitor from the leech Hirudinaria a potent inhibitor, analogous to eglin, was also detected. Results indicate that this inhibitor, which we have named 'GELIN', is significantly different from eglin. Gelin was isolated and purified to homogeneity by ion exchange chromatography and reverse phase HPLC. The isoelectric point of Gelin was estimated to be 4.55, in contrast to 6.45 for eglin. The molecular weight of Gelin was similar to eglin, as estimated by SDS-PAGE. Amino-terminal sequence analysis of the first 29 residues show no sequence homology with eglin or any other serine protease inhibitors. Circular dichroism studies showed that the secondary structure of Gelin has no helix, 58% beta sheets and 42% random structures compared to 19% helix, 56% beta sheets and 25% random structures in eglin. Like eglin, Gelin inhibits elastase, cathepsin G and chymotrypsin but has little or no activity towards plasmin, thrombin, pepsin and trypsin. These data suggest that the elastase inhibitors from these two species of leech are fundamentally different in structure, indicative of independent evolutionary origin.
The Role of Protein Glycosylation in Allergy (2006)

The asparagine-linked carbohydrate moieties of plant and insect glycoproteins are the most abundant environmental immune determinants. They are the structural basis of what is known as cross-reactive carbohydrate determinants (CCDs). Despite some structural variation, the two main motifs are the xylose and the core-3-linked fucose, which form the essential part of two independent epitopes. Plants contain both epitopes, insect glycoproteins only fucose. These epitopes and other fucosylated determinants are also found in helminth parasites where they exert remarkable immunomodulatory effects. About 20% or more of allergic patients generate specific anti-glycan IgE, which is often accompanied by IgG. Even though antibody-binding glycoproteins are widespread in pollens, foods and insect venoms, CCDs do not appear to cause clinical symptoms in most, if not all patients. When IgE binding is solely due to CCDs, a glycoprotein allergen thus can be rated as clinical irrelevant allergen. Low binding affinity between IgE and plant N-glycans now drops out as a plausible explanation for the benign nature of CCDs. This rather may result from blocking antibodies induced by an incidental 'immune therapy' ('glyco-specific immune therapy') exerted by everyday contact with plant materials, e.g. fruits or vegetables. The need to detect and suppress anti-CCD IgE without interference from peptide epitopes can be best met by artificial glycoprotein allergens. Hydroxyproline-linked arabinose (single beta-arabinofuranosyl residues) has been identified as a new IgE-binding carbohydrate epitope in the major mugwort allergen. However, currently the occurrence of this O-glycan determinant appears to be rather restricted.
Nuclear Double Resonance in the Rotating Frame (1962)

A double nuclear resonance spectroscopy method is introduced which depends upon effects of magnetic dipole-dipole coupling between two different nuclear species. In solids a minimum detectability of the order of ${10}^{14}$ to ${10}^{16}$ nuclear Bohr magnetons/cc of a rare $b$ nuclear species is predicted, to be measured in terms of the change in a strong signal displayed by an abundant $a$ nuclear species. The $a$ magnetization is first oriented by a strong radio-frequency field in the frame of reference rotating at its Larmor frequency. The $b$ nuclear resonance is obtained simultaneously with a second radio-frequency field; and with the condition that the $a$ and $b$ spins have the same Larmor frequencies in their respective rotating frames, a cross relaxation will occur between the two spin systems. The cross-relaxation interaction, which lasts for the order of a long spin-lattice relaxation time of the $a$ magnetization, is arranged to produce a cumulative demagnetization of the $a$ system when maximum sensitivity is desired. Final observation of the reduced $a$ magnetization indicates the nuclear resonance of the $b$ system. The concepts of uniform spin temperature, when it is valid, and of nonuniform spin temperature where spin diffusion is important, are applied. The density matrix method formulates the double resonance interaction rate in second order. Preliminary tests of the double resonance effect are carried out with a nuclear quadrupole system.
A phase Ib study of the Akt inhibitor GDC-0068 with docetaxel (D) or mFOLFOX-6 (F) in patients (pts) with advanced solid tumors. (2012)

3021 Background: Activation of the Akt pathway is observed in multiple tumors and may contribute to chemoresistance. GDC-0068 is an ATP-competitive small molecule inhibitor of all three isoforms of Akt; in a phase Ia study, it was well tolerated with maximum tolerated dose (MTD) of 600 mg daily (21 days on/7days off) and pharmacodynamic down-regulation of Akt signaling in tumors at doses ≥100 mg. In vitro, GDC-0068 shows synergism with cytotoxic agents. This phase Ib study defines the dose limiting toxicities (DLT), MTD, safety and pharmacokinetics (PK) of GDC0068 in combination with D and F. Methods: Using a 3+3 designeligible patients (pt) with advanced/metastatic solid tumors were treated with either D, 75 mg/m 2 day 1 and GDC-0068 daily on days 2-15 of a 21 day cycle (Arm A); or F, bolus 5FU 400mg/m 2 , leucovorin 400 mg/m 2 , oxaliplatin 85 mg/m 2 all day 1, and infusional 5FU 2400mg/m 2 for 46 hours and GDC-0068 daily on days 1-7 of a 14 day cycle (Arm B). PK sampling was performed in Cycles 1 and 2. Results: 23 pts have enrolled; Arm A (GDC-0068, mg): 100 (n=3), 200 (n=4), and 400 (n=5); Arm B:100 (n=6) and 200 (n=5). Median prior therapies = 3. GDC-0068-related adverse events in ≥ 10% of pts were diarrhea, nausea, vomiting, fatigue, and decreased appetite. All GDC-0068-related AEs were grade 1 or 2, except one grade 4 neutropenia in Arm A. No DLTs have been reported to date. Preliminary data show no alteration in the PK of GDC-0068, D or F compared to phase Ia or historical data. Two heavily pretreated pts with cervical and PTEN-loss colon cancers treated in Arm B demonstrated both RECIST partial response and tumor marker decrease by first CT evaluation. Conclusions: The combination of GDC-0068 with D or F is well-tolerated and shows early signs of anti-tumor activity. Dose-escalations continue.