gebhart/patrepeval huggingface dataset:
Quantitative analysis of the EGF receptor autocrine system reveals cryptic regulation of cell response by ligand capture (2001)

Autocrine signaling is important in normal tissue physiology as well as pathological conditions. It is difficult to analyze these systems, however, because they are both self-contained and recursive. To understand how parameters such as ligand production and receptor expression influence autocrine activity, we investigated a human epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) loop engineered into mouse B82 fibroblasts. We varied the level of ligand production using the tet-off expression system and used metalloprotease inhibitors to modulate ligand release. Receptor expression was varied using antagonistic blocking antibodies. We compared autocrine ligand release with receptor activation using a microphysiometer-based assay and analyzed our data using a quantitative model of ligand release and receptor dynamics. We found that the activity of our autocrine system could be described in terms of a simple ratio between the rate of ligand production (V(LT)) and the rate of receptor production (V(R)). At a V(LT)/V(R) ratio of <0.3, essentially no ligand was found in the extracellular medium, but a significant number of cell receptors (30-40%) were occupied. As the V(LT)/V(R) ratio increased from 0.3 towards unity, receptor occupancy increased and significant amounts of ligand appeared in the medium. Above a V(LT)/V(R) ratio of 1.0, receptor occupancy approached saturation and most of the released ligand was lost into the medium. Analysis of human mammary epithelial cells showed that a V(LT)/V(R) ratio of < 5 x 10(-4)was sufficient to evoke >20% of a maximal proliferative response. This demonstrates that natural autocrine systems can be active even when no ligand appears in the extracellular medium.
Molecular requirements for immunoglobulin heavy chain constant region gene switch recombination revealed with switch substrate retroviruses (1989)

We have employed a retroviral vector, ZN(Smu/S gamma 2b)tk1, as a means of introducing immunoglobulin heavy chain (IgH) switch (S) region sequences into B cell lines to directly measure their switch-recombinase activities. In an earlier study, we demonstrated that retrovector Smu-S gamma 2b recombination events occurred in two thymidine kinase (tk)-negative murine pre-B cell lines (18-8 and 38B9) upon selection in bromodeoxyuridine (BUdR) media for the loss of an Htk gene inserted in between the vector's Smu and S gamma 2b sequences. Here we have used this assay system to show that the 300-18 murine pre-B cell line possesses a very high level of switch-recombinase activity (greater than 1 event in 2500 cells/generation) while a terminally differentiated, antibody-secreting hybridoma line (A39R 1.1) has no detectable recombinase activity. Both S mu and S gamma 2b segments are required for switch region-mediated deletions. Retrovectors harboring only an Smu segment or an Smu segment and a portion of the murine c-myc gene in place of S gamma 2b sequences were both non-recombinagenic in this assay system. Nucleotide sequence analysis of six retrovector S segment recombinants, recovered from ZN(Smu/S gamma 2b) tk1-infected 18-8 and 39B9 pre-B lines, did not reveal homology at their sites of recombination. We conclude that: (1) S segment repetitive sequences play an essential but indirect role in IgCH gene switch-recombination, which occurs by an illegitimate, non-homologous mechanism; (2) the c-myc gene is not a significant target for switch-recombination; and (3) since endogenous Smu and S gamma 2b rearrangements were not observed in populations and clones of pre-B cells expressing a high level of switch-recombinase activity, multiple factors (presumably contributed in part by the degree of S segment accessibility) in addition to S recombinase activity are required for CH class switching.
Specific treatment of autoimmunity with recombinant invariant chains in which CLIP is replaced by self-epitopes (2001)

The invariant chain (Ii) binds to newly synthesized MHC class II molecules with the CLIP region of Ii occupying the peptide-binding groove. Here we demonstrate that recombinant Ii proteins with the CLIP region replaced by antigenic self-epitopes are highly efficient in activating and silencing specific T cells in vitro and in vivo. The Ii proteins require endogenous processing by antigen-presenting cells for efficient T cell activation. An Ii protein encompassing the epitope myelin basic protein amino acids 84-96 (Ii-MBP84-96) induced the model autoimmune disease experimental allergic encephalomyelitis (EAE) with a higher severity and earlier onset than the peptide. When applied in a tolerogenic manner, Ii-MBP84-96 abolished antigen-specific T cell proliferation and suppressed peptide-induced EAE more effectively than peptide alone. Importantly, i.v. administration of Ii proteins after EAE induction completely abrogated the disease, whereas peptides only marginally suppressed disease symptoms. Ii fusion proteins are thus more efficient than peptide in modulating CD4(+) T cell-mediated autoimmunity, documenting their superior qualities for therapeutic antigen delivery in vivo.
Nerve Growth Factor Treatment Increases Brain-Derived Neurotrophic Factor Selectively in TrkA-Expressing Dorsal Root Ganglion Cells and in Their Central Terminations within the Spinal Cord (1997)

Using immunocytochemistry and in situ hybridization, we have examined the expression of brain-derived neurotrophic factor (BDNF) and of neurotrophin receptors in dorsal root ganglion cells. In the adult rat, BDNF mRNA and protein were found mainly in the subpopulation of cells that express the nerve growth factor (NGF) receptor trkA and the neuropeptide calcitonin gene-related peptide (CGRP). NGF increased BDNF within the trkA/CGRP cells to the extent that almost 90% of trkA cells contained BDNF mRNA after intrathecal NGF treatment, and 80-90% of BDNF-expressing cells contained trkA. Non-trkA cells that expressed BDNF included some trkC cells and some small cells that labeled with the lectin Griffonia simplicifolia IB4, a marker for cells that do not express trks. However, very few trkB cells expressed either BDNF mRNA or protein, and NGF did not increase BDNF expression in non-trkA cells. BDNF protein was anterogradely transported both peripherally and centrally. The central transport resulted in BDNF immunoreactivity in CGRP containing terminal arbors in the dorsal horn of the spinal cord, and this immunoreactivity was increased by NGF treatment. Electron microscopic analysis revealed that the BDNF immunoreactivity was present in finely myelinated and unmyelinated axons and in axon terminals, where it was most concentrated over dense-cored vesicles. Our data do not support an autocrine or paracrine role for BDNF within normal dorsal root ganglia, but indicate that BDNF may act as an anterograde trophic messenger. NGF levels in the periphery could influence dorsal horn neurons via release of BDNF from primary afferents.
Dual-Energy CT as a Potential New Diagnostic Tool in the Management of Gout in the Acute Setting (2010)

The ability of dual-energy CT to diagnose early gout and its use as a problem-solving tool is shown here. Diagnosis of subclinical gout could avert associated long-term complications, thereby reducing disease burden and improving overall quality of life.
Bayesian classification of protein structure (1992)

The application of an Autoclass III machine-learning algorithm for heuristic Bayesian classification to independently confirm and provide new information about structural classes of proteins is discussed. Bayesian classification and Autoclass III systems are reviewed. The decisions concerning and data representations and where to begin searching the space of potential classifications are discussed. Results of the application, in terms of classification patterns, relationship to traditional classes, higher-order structure, and class composition, are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Chimeric Receptor mRNA Transfection as a Tool to Generate Antineoplastic Lymphocytes (2009)

mRNA transfection is a useful approach for temporal cell reprogramming with minimal risk of transgene-mediated mutagenesis. We applied this to redirect lymphocyte cytotoxicity toward malignant cells. Using the chimeric immune receptor (CIR) constructs anti-CD19 CIR and 8H9 CIR, we achieved uniform expression of CIRs on virtually the entire population of lymphocytes. We reprogrammed CD3+ CD8+, CD3+ CD4+, and natural killer (NK ) cells toward autologous and allogeneic targets such as B cells, Daudi lymphoma, primary melanoma, breast ductal carcinoma, breast adenocarcinoma, and rhabdomyosarcoma. The reprogramming procedure is fast. Although most of the experiments were performed on lymphocytes obtained after 7-day activation, only 1-day activation of T cells with anti-CD3, anti-CD28 antibodies, and interleukin-2 is sufficient to develop both lymphocyte cytotoxicity and competence for mRNA transfer. The entire procedure, which includes lymphocyte activation and reprogramming, can be completed in 2 days. The efficiency of mRNA-modified human T cells was tested in a murine xenograft model. Human CD3+CD8+ lymphocytes expressing anti-CD19 CIR mRNA inhibited Daudi lymphoma growth in NOD=SCID mice. These results demonstrate that a mixed population of cytotoxic lymphocytes, including T cells together with NK cells, can be quickly and simultaneously reprogrammed by mRNA against autologous malignancies. With relatively minor modifications the described method of lymphocyte reprogramming can be scaled up for cancer therapy.
Crystal Structure of Human Pirin (2004)

Pirin is a newly identified nuclear protein that interacts with the oncoprotein B-cell lymphoma 3-encoded (Bcl-3) and nuclear factor I (NFI). The crystal structure of human Pirin at 2.1-A resolution shows it to be a member of the functionally diverse cupin superfamily. The structure comprises two beta-barrel domains, with an Fe(II) cofactor bound within the cavity of the N-terminal domain. These findings suggest an enzymatic role for Pirin, most likely in biological redox reactions involving oxygen, and provide compelling evidence that Pirin requires the participation of the metal ion for its interaction with Bcl-3 to co-regulate the NF-kappaB transcription pathway and the interaction with NFI in DNA replication. Substitution of iron by heavy metals thus provides a novel pathway for these metals to directly influence gene transcription. The structure suggests an interesting new role of iron in biology and that Pirin may be involved in novel mechanisms of gene regulation.
Testicular GATA-1 Factor Up-Regulates the Promoter Activity of Rat Inhibin α-Subunit Gene in MA-10 Leydig Tumor Cells (1998)

We have previously demonstrated that the basal transcription of rat inhibin alpha-subunit gene in a mouse testicular Leydig tumor cell line, MA-10, depends upon a 67-bp DNA fragment at the position of -163 to -97. Within this promoter region two GATA motifs were observed. In this study, we investigated the possible role of GATA-binding proteins in the regulation of inhibin alpha-subunit gene transcription in testicular cells. Northern blot and RT-PCR analyses showed that mRNAs encoding GATA-binding proteins, GATA-1 and GATA-4, were detected in mouse and rat testis and in MA-10 and rat Sertoli cells. Testis-specific GATA-1 mRNA, which is transcribed from a promoter 8 kb upstream to the erythroid exon I of mouse GATA-1 gene, was also identified in MA-10 cells. Mutations of GATA sequences in alpha-subunit promoter markedly decreased the transcriptional activity of alpha-subunit gene when measured by their ability of transient expression of a bacterial reporter gene, chloramphenicol acetyltransferase (CAT), in MA-10 cells. Cotransfection of alphaCAT chimeric construct with cDNA expression plasmid coding for mouse GATA-1 or GATA-4 protein revealed that GATA-1 but not GATA-4 can transactivate alpha-subunit promoter in a dose-dependent manner. The transactivation by GATA-1 was inhibited if GATA sequences in alpha-subunit promoter were mutated. Furthermore, electrophoretic mobility shift assay demonstrated that GATA-binding proteins present in nuclear extracts of MA-10 cells and rat testis interacted with the GATA motifs in alpha-subunit promoter, and the GATA-1 in these nuclear extracts formed a supershifted immunocomplex with antibody raised against mouse GATA-1 protein. We therefore concluded that the basal transcription of inhibin alpha-subunit gene in testicular MA-10 cells is up-regulated by testicular GATA-1 but not GATA-4 through its interaction with the GATA motifs in alpha-subunit promoter. In summary, we have provided the first evidence of the functional role of a GATA-binding protein in the regulation of testicular gene expression.
Controlled topology simplification (1996)

We present a simple, robust, and practical method for object simplification for applications where gradual elimination of high frequency details is desired. This is accomplished by converting an object into multi resolution volume rasters using a controlled filtering and sampling technique. A multiresolution triangle mesh hierarchy can then be generated by applying the Marching Cubes algorithm. We further propose an adaptive surface generation algorithm to reduce the number of triangles generated by the standard Marching Cubes. Our method simplifies the topology of objects in a controlled fashion. In addition, at each level of detail, multilayered meshes can be used for an efficient antialiased rendering.
BioGPS: an extensible and customizable portal for querying and organizing gene annotation resources (2009)

Online gene annotation resources are indispensable for analysis of genomics data. However, the landscape of these online resources is highly fragmented, and scientists often visit dozens of these sites for each gene in a candidate gene list. Here, we introduce BioGPS http://biogps.gnf.org, a centralized gene portal for aggregating distributed gene annotation resources. Moreover, BioGPS embraces the principle of community intelligence, enabling any user to easily and directly contribute to the BioGPS platform.
A rapid in situ procedure for determination of bacterial susceptibility or resistance to antibiotics that inhibit peptidoglycan biosynthesis (2011)

The technique to assess cell wall integrity appears to be a rapid and simple procedure to identify resistant and susceptible strains to antibiotics that interfere with peptidoglycan biosynthesis.
Human NELL-1 Expressed in Unilateral Coronal Synostosis (1999)

Surgical correction of unilateral coronal synostosis offers a unique opportunity to examine the molecular differences between an abnormal and a normal cranial suture. We isolated and identified a cDNA fragment whose expression was up-regulated in the premature fusing and fused coronal sutures, as compared with normal coronal sutures. The nucleotide sequence of the full-length cDNA of this gene, human NELL-1, has approximately 61% homology with the chicken Nel gene. Both chicken Nel and human NELL-1 are comprised of six epidermal growth factor-like repeats. The human NELL-1 messages were localized primarily in the mesenchymal cells and osteoblasts at the osteogenic front, along the parasutural bone margins, and within the condensing mesenchymal cells of newly formed bone in sites of premature sutural fusion. Human multiorgan tissue mRNA blot showed that NELL-1 was specifically expressed in fetal brain but not in fetal kidney, liver, or lung. We also showed that Nell-1 was expressed in rat calvarial osteoprogenitor cells and was largely absent in rat tibiae and fibroblast cell cultures. In conclusion, our data suggest that the NELL-1 gene is preferentially expressed in cranial intramembranous bone and neural tissue (both of neural crest cell origin) and is up-regulated during unilateral premature closure of the coronal suture. The precise role of this gene is unknown.
[Atrial natriuretic peptide. I: Biochemistry, general pharmacology and physiology. A review]. (1990)

The recent discovery of the atrial natriuretic peptide (ANP) system and its possible physiological role in mammalians is discussed. The atrium is the major site of synthesis for ANP, where it is stored in specific secretory granules of atrial myocytes as a 126 amino acid precursor molecule (ANP 1-126). Upon adequate stimuli, such as atrial distension, the biologically active ANP (99-126) is released into the circulation. The hormone binds to specific receptors of the target organs, provoking natriuresis, diuresis, vasodilatation and exerts an inhibitory effect on the renin-angiotensin-aldosterone system. The peptide seems to play a role in cardiovascular regulation by both its renal and extrarenal actions.
Applying Bayesian networks to information retrieval (1995)

Information retrieval (IR) is the identification of documents or other units of information in a collection that are relevant to a particular information need. An information need is a set of questions to which someone would like to find an answer. Here are some examples of IR tasks: finding articles in the New York Times that discuss the Iran-Contra affair; searching the recent postings in a Usenet newsgroup for references to a particular model of personal computer; finding the entries referring to butterflies in an online CD-ROM encyclopedia.
Re: Is On-Demand Sacral Neuromodulation in Patients with OAB Syndrome a Feasible Therapy Regime? (2012)

No AccessJournal of UrologyAdult Urology1 Feb 2013Re: Is On-Demand Sacral Neuromodulation in Patients with OAB Syndrome a Feasible Therapy Regime? Alan J. WeinM.D., Ph.D. (hon.) Alan J. WeinAlan J. Wein More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.10.127AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Re: Is On-Demand Sacral Neuromodulation in Patients with OAB Syndrome a Feasible Therapy Regime?." The Journal of Urology, 189(2), pp. 610–611 © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 2February 2013Page: 610-611 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alan J. Wein More articles by this author Expand All Advertisement Loading ...
Ciliary neurotrophic factor induces cholinergic differentiation of rat sympathetic neurons in culture. (1989)

Ciliary neurotrophic factor (CNTF) influences the levels of choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) in cultures of dissociated sympathetic neurons from newborn rats. In the presence of CNTF both the total and specific activity of ChAT was increased 7 d after culture by 15- and 18-fold, respectively, as compared to cultures kept in the absence of CNTF. Between 3 and 21 d in culture in the presence of CNTF the total ChAT activity increased by a factor of greater than 100. Immunotitration demonstrated that the elevated ChAT levels were due to an increased number of enzyme molecules. In contrast to the increase in ChAT levels, the total and specific activity levels of TH were decreased by 42 and 36%, respectively, after 7 d in culture. Half-maximal effects for both ChAT increase and TH decrease were obtained at CNTF concentrations of approximately 0.6 ng and maximal levels were reached at 1 ng of CNTF per milliliter of medium. The effect of CNTF on TH and ChAT levels were seen in serum-containing medium as well as in serum-free medium. CNTF was shown to have only a small effect on the long-term survival of rat sympathetic neurons. We therefore concluded that the effects of CNTF on ChAT and TH are not due to selective survival of cells that acquire cholinergic traits in vitro, but are rather due to the induction of cholinergic differentiation of noradrenergic sympathetic neurons.
A Hybrid Rule/Model-Based Finite-State Framework for Normalizing SMS Messages (2010)

In recent years, research in natural language processing has increasingly focused on normalizing SMS messages. Different well-defined approaches have been proposed, but the problem remains far from being solved: best systems achieve a 11% Word Error Rate. This paper presents a method that shares similarities with both spell checking and machine translation approaches. The normalization part of the system is entirely based on models trained from a corpus. Evaluated in French by 10-fold-cross validation, the system achieves a 9.3% Word Error Rate and a 0.83 BLEU score.
Deoxycholic Acid Activates β-Catenin Signaling Pathway and Increases Colon Cell Cancer Growth and Invasiveness (2004)

Colorectal cancer is often lethal when invasion and/or metastasis occur. Tumor progression to the metastatic phenotype is mainly dependent on tumor cell invasiveness. Secondary bile acids, particularly deoxycholic acid (DCA), are implicated in promoting colon cancer growth and progression. Whether DCA modulates beta-catenin and promotes colon cancer cell growth and invasiveness remains unknown. Because beta-catenin and its target genes urokinase-type plasminogen activator receptor (uPAR) and cyclin D1 are overexpressed in colon cancers, and are linked to cancer growth, invasion, and metastasis, we investigated whether DCA activates beta-catenin signaling and promotes colon cancer cell growth and invasiveness. Our results show that low concentrations of DCA (5 and 50 microM) significantly increase tyrosine phosphorylation of beta-catenin, induce urokinase-type plasminogen activator, uPAR, and cyclin D1 expression and enhance colon cancer cell proliferation and invasiveness. These events are associated with a substantial loss of E-cadherin binding to beta-catenin. Inhibition of beta-catenin with small interfering RNA significantly reduced DCA-induced uPAR and cyclin D1 expression. Blocking uPAR with a neutralizing antibody significantly suppressed DCA-induced colon cancer cell proliferation and invasiveness. These findings provide evidence for a novel mechanism underlying the oncogenic effects of secondary bile acids.
Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4 (2014)

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory receptor found on immune cells. The consequences of mutations in CTLA4 in humans are unknown. We identified germline heterozygous mutations in CTLA4 in subjects with severe immune dysregulation from four unrelated families. Whereas Ctla4 heterozygous mice have no obvious phenotype, human CTLA4 haploinsufficiency caused dysregulation of FoxP3(+) regulatory T (Treg) cells, hyperactivation of effector T cells, and lymphocytic infiltration of target organs. Patients also exhibited progressive loss of circulating B cells, associated with an increase of predominantly autoreactive CD21(lo) B cells and accumulation of B cells in nonlymphoid organs. Inherited human CTLA4 haploinsufficiency demonstrates a critical quantitative role for CTLA-4 in governing T and B lymphocyte homeostasis.
A genetically encoded fluorescent sensor of ERK activity (2008)

The activity of the ERK has complex spatial and temporal dynamics that are important for the specificity of downstream effects. However, current biochemical techniques do not allow for the measurement of ERK signaling with fine spatiotemporal resolution. We developed a genetically encoded, FRET-based sensor of ERK activity (the extracellular signal-regulated kinase activity reporter, EKAR), optimized for signal-to-noise ratio and fluorescence lifetime imaging. EKAR selectively and reversibly reported ERK activation in HEK293 cells after epidermal growth factor stimulation. EKAR signals were correlated with ERK phosphorylation, required ERK activity, and did not report the activities of JNK or p38. EKAR reported ERK activation in the dendrites and nucleus of hippocampal pyramidal neurons in brain slices after theta-burst stimuli or trains of back-propagating action potentials. EKAR therefore permits the measurement of spatiotemporal ERK signaling dynamics in living cells, including in neuronal compartments in intact tissues.