gebhart/patrepeval huggingface dataset:
G9a, a multipotent regulator of gene expression (2012)

Lysine methylation of histone and non-histone substrates by the methyltransferase G9a is mostly associated with transcriptional repression. Recent studies, however, have highlighted its role as an activator of gene expression through mechanisms that are independent of its methyltransferase activity. Here we review the growing repertoire of molecular mechanisms and substrates through which G9a regulates gene expression. We also discuss emerging evidence for its wide-ranging functions in development, pluripotency, cellular differentiation and cell cycle regulation that underscore the complexity of its functions. The deregulated expression of G9a in cancers and other human pathologies suggests that it may be a viable therapeutic target in various diseases.
Vectored Expression of the Broadly Neutralizing Antibody FI6 in Mouse Airway Provides Partial Protection against a New Avian Influenza A Virus, H7N9 (2013)

As of 4 July 2013, there have been 134 confirmed cases of human infection and 43 fatalities with a new avian influenza A virus (H7N9) ([1][1]). H7N9 is currently contained in Southeastern China, and the majority of human cases of infection have reported direct exposure to poultry ([2][2]). While no
Staging of Alzheimer-Related Cortical Destruction (1993)

The gradual intraneuronal accumulation of an insoluble fibrous material which partly consists of abnormally phosphorylated tau protein (neurofibrillary change) represents an important neuropathological hallmark of Alzheimer's disease. Neurofibrillary tangles and neuropil threads formed from this material develop in only a few types of cortical pyramidal cells. The first changes are seen in the entorhinal cortex. The destructive process then spreads into the hippocampal formation and eventually encroaches upon the isocortex. This sequence of events permits the distinction of six stages with a progressive increase in the severity of cortical destruction. The entorhinal region serves as an important interface between the isocortex and hippocampus. This interface function is markedly impaired due to the early deterioration of the entorhinal cortex. Severe entorhinal involvement is considered to represent the morphological counterpart of clinically incipient Alzheimer's disease. Similar changes are found in mentally impaired individuals suffering from Parkinson's disease or progressive supranuclear palsy.
The use of engineered E1A genes to transactivate the hCMV-MIE promoter in permanent CHO cell lines (1991)

Vectors expressing adenovirus 5 E1A or a domain 2 mutant E1A were introduced into CHO-K1 cells in order to transactivate the hCMV-MIE promoter in transient and stable transfections. Expression from the hCMV promoter was efficiently activated by both wild-type and mutant E1A in contrast to other viral promoters such as the SV40 early promoter which are repressed by E1A. E1A genes expressed from a strong promoter were inhibitory to the growth of CHO cells. Nevertheless, by the use of a weaker promoter, it was possible to isolate stably transfected cell lines containing a level of E1A compatible with both continued cell growth and significant transactivation of the hCMV promoter. By this means we have generated cell lines secreting tissue inhibitor of metalloproteinases (TIMP) at levels approaching those previously attained using gene amplification. CHO cell lines constitutively expressing wild-type and mutant E1A genes have been derived which can serve as new host cell lines for transient expression and efficient stable expression without gene amplification.
A β-Arrestin/Green Fluorescent Protein Biosensor for Detecting G Protein-coupled Receptor Activation (1997)

G protein-coupled receptors (GPCR) represent the single most important drug targets for medical therapy, and information from genome sequencing and genomic data bases has substantially accelerated their discovery. The lack of a systematic approach either to identify the function of a new GPCR or to associate it with a cognate ligand has added to the growing number of orphan receptors. In this work we provide a novel approach to this problem using a beta-arrestin2/green fluorescent protein conjugate (betaarr2-GFP). It provides a real-time and single cell based assay to monitor GPCR activation and GPCR-G protein-coupled receptor kinase or GPCR-arrestin interactions. Confocal microscopy demonstrates the translocation of betaarr2-GFP to more than 15 different ligand-activated GPCRs. These data clearly support the common hypothesis that the beta-arrestin binding of an activated receptor is a convergent step of GPCR signaling, increase by 5-fold the number of GPCRs known to interact with beta-arrestins, demonstrate that the cytosol is the predominant reservoir of biologically active beta-arrestins, and provide the first direct demonstration of the critical importance of G protein-coupled receptor kinase phosphorylation to the biological regulation of beta-arrestin activity and GPCR signal transduction in living cells. The use of betaarr2-GFP as a biosensor to recognize the activation of pharmacologically distinct GPCRs should accelerate the identification of orphan receptors and permit the optical study of their signal transduction biology intractable to ordinary biochemical methods.
Multicolor fluorescence in situ hybridization for the simultaneous detection of probe sets for chromosomes 13, 18, 21, X and Y in uncultured amniotic fluid cells (1992)

The most frequent aneuploidies in newborns involve the autosomes 13, 18 and 21 as well as both sex chromosomes. Fluorescence in situ hybridization readily allows the detection of numerical chromosomal aberrations throughout all stages of the cell cycle. Using a multicolor fluorescence in situ hybridization approach based on combinatorial probe labeling and digital imaging microscopy we demonstrate the simultaneous visualization of probe sets specific for chromosomes 13, 18, 21, X and Y. This approach enables one to evaluate aberrations of multiple chromosomes in a single hybridization experiment using metaphase chromosomes and interphase nuclei from a variety of cell types, including lymphocytes and amniocytes.
A randomized placebo-controlled trial of erlotinib in patients with advanced non-small cell lung cancer (NSCLC) following failure of 1st line or 2nd line chemotherapy. A National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trial (2004)

7022 Background: In phase II studies, erlotinib has shown single agent activity in a number of tumor types, including NSCLC. NCIC CTG BR.21 is a randomized, placebo-controlled trial undertaken to determine if the Epidermal Growth Factor Receptor (EGFR) inhibitor erlotinib (Tarceva) prolongs survival in NSCLC patients after 1st or 2nd line chemotherapy. Methods: Eligibility criteria included stage IIIB/IV NSCLC, PS 0–3, 1–2 chemotherapy regimens (at least 1 combination regimen if < 70 yrs). Patients were stratified by center, PS (0,1 v 2,3), response to chemo (CR, PR v SD v PD), number of prior regimens (1 v 2), platinum (yes v no), and were randomized 2:1 to receive erlotinib 150 mg po/day or placebo. The 10 endpoint was survival with 20 endpoints of progression free survival (PFS), response, toxicity and QOL. Results: From Nov/01-Feb/03, 731 pts entered the study (median age 61y; 64% male; 67% PS 0,1). 50% had received 2 prior regimens, 93% had received platinum and 37% prior taxanes. Patient characteristics were well balanced. Overall response to erlotinib was 8.9% (95% CI: 6.6–12.0%, p < 0.001), median duration 34.2 wks. Statistically significant and clinically relevant differences were observed for overall survival and PFS. The planned primary QOL analysis, time to deterioration of patient reported symptoms (TTDS), showed statistically and clinically meaningful benefit for patients randomized to erlotinib. Rash and diarrhea were the most frequent symptoms; 5% of patients discontinued erlotinib for toxicity compared to 2% of patients on placebo. Conclusion: This is the first randomized trial to confirm that a Her1/EGFR inhibitor prolongs survival after 1st or 2nd line chemotherapy for NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration OSI Pharmaceuticals OSI Pharmaceuticals OSI Pharmaceuticals partially funded by a grant to the National Cancer Institute of Canada Clinical Trials Group from OSI Pharmaceuticals
Liposomal Nanomedicines: An Emerging Field (2008)

Liposomal nanoparticles (LNs) encapsulating therapeutic agents, or liposomal nanomedicines (LNMs), represent one of the most advanced classes of drug delivery systems, with several currently on the market and many more in clinical trials. During the past 20 years, a variety of techniques have been developed for encapsulating both conventional drugs and the new genetic drugs (plasmid DNA-containing therapeutic genes, antisense oligonucleotides, and small, interfering RNA [siRNA]) within LNs encompassing a very specific set of properties: a diameter centered on 100 nm, a high drug-to-lipid ratio, excellent retention of the encapsulated drug, and a long (>6 hours) circulation lifetime. Particles with these properties tend to accumulate at sites of disease, such as tumors, where the endothelial layer is "leaky" and allows extravasation of particles with small diameters. Thus, LNs protect the drug during circulation, prevent it from reaching healthy tissues, and permit its accumulation at sites of disease. We will discuss recent advances in this field involving conventional anticancer drugs as well as gene-delivery, immunostimulatory, and gene-silencing applications involving the new genetic drugs. LNMs have the potential to offer new treatments in such areas as cancer therapy, vaccine development, and cholesterol management.
Fatty Acid Metabolism (1988)

Crop loss due to soil salinization is an increasing threat to agriculture worldwide. This review provides an overview of cellular and physiological mechanisms in plant responses to salt. We place cellular responses in a time- and tissue-dependent context ...Read More
cdc25 is one of the MPM-2 antigens involved in the activation of maturation-promoting factor. (1994)

MPM-2 antigens, a discrete set of phosphoproteins that contain similar phosphoepitopes recognized by the monoclonal antibody MPM-2, are phosphorylated during M-phase induction. Our previous studies suggested that certain MPM-2 antigens are involved in the appearance of maturation-promoting factor (MPF) activity. Because the central mitotic regulator cdc2 kinase has been shown to exhibit MPF activity, we explored the possibility that certain MPM-2 antigens are regulators of cdc2 kinase. We found that MPM-2 binding of its antigens would inhibit the autoamplification of cdc2 kinase in Xenopus oocytes and interfere with cyclin-activation of cdc2 kinase in Xenopus interphase egg extract. Immunodepletion of MPM-2 antigens from cyclin-induced M-phase egg extract caused the inactivation of cdc2 kinase, which was accompanied by an inhibitory phosphorylation of p34cdc2 on Thr 14 and Tyr 15, indicating that at least one MPM-2 antigen is a positive regulator of p34cdc2 dephosphorylation. We then showed that cdc25 from M-phase arrested egg extract is an MPM-2 antigen. These results suggest that phosphorylation of the epitope recognized by MPM-2 may be a crucial event in the activation of cdc25 and that the kinase(s) that phosphorylates this MPM-2 epitope may be an important regulator of cdc2 kinase activation.
Interactions between mature Der p 1 and its free prodomain indicate membership of a new family of C1 peptidases (2007)

Mature Der p 1-prodomain interactions differ from other C1 family cysteine peptidases, suggesting that group 1 mite allergens are a new subgroup among C1 family cysteine peptidases. The rapid inactivation of Der p 1 prodomain is a newly identified mechanism that may contribute to the potency of this allergen.
Parameter estimation and optimal control of swarm-robotic systems: A case study in distributed task allocation (2008)

This paper presents a methodology for finding optimal control parameters as well as optimal system parameters for robot swarm controllers using probabilistic, population dynamic models. With distributed task allocation as a case study, we show how optimal control parameters leading to a desired steady-state task distribution for two fully-distributed algorithms can be found even if the parameters of the system are unknown. First, a reactive algorithm in which robots change states independently from each other and which leads to a linear macroscopic model describing the dynamics of the system is considered. Second, a threshold-based algorithm where robots change states based on the number of other robots in this state and which leads to a non-linear model is investigated. Whereas analytical results can be obtained for the linear system, the optimization of the non-linear controller is performed numerically. Finally, we show using stochastic simulations that whereas the presented methodology and models work best if the swarm size is large, useful results can already be obtained for team-sizes below a hundred robots. The methodology presented can be applied to scenarios involving the control of large numbers of entities with limited computational and communication abilities as well as a tight energy budget, such as swarms of robots from the centimeter to nanometer range or sensor networks.
Gray platelet syndrome: proinflammatory megakaryocytes and α-granule loss cause myelofibrosis and confer metastasis resistance in mice (2014)

NBEAL2 encodes a multidomain scaffolding protein with a putative role in granule ontogeny in human platelets. Mutations in NBEAL2 underlie gray platelet syndrome (GPS), a rare inherited bleeding disorder characterized by a lack of α-granules within blood platelets and progressive bone marrow fibrosis. We present here a novel Nbeal2(-/-) murine model of GPS and demonstrate that the lack of α-granules is due to their loss from platelets/mature megakaryocytes (MKs), and not by initial impaired formation. We show that the lack of Nbeal2 confers a proinflammatory phenotype to the bone marrow MKs, which in combination with the loss of proteins from α-granules drives the development of bone marrow fibrosis. In addition, we demonstrate that α-granule deficiency impairs platelet function beyond their purely hemostatic role and that Nbeal2 deficiency has a protective effect against cancer metastasis.
Optimal Rearrangeable Multistage Connecting Networks (1964)

A rearrangeable connecting network is one whose permitted states realize every assignment of inlets to outlets — that is, one in which it is possible to rearrange existing calls so as to put in any new call. In the effort to provide adequate telephone service with efficient networks it is of interest to be able to select rearrangeable networks (from suitable classes) having a minimum number of crosspoints. This problem is fully resolved for the class of connecting networks built of stages of identical square switches arranged symmetrically around a center stage: roughly, the optimal network should have as many stages as possible, with switches that are as small as possible, the largest switches being in the center stage; the cost (in crosspoints per inlet) of an optimal network of N inlets and N outlets is nearly twice the sum of the prime divisors of N, while the number of its stages is 2×−1, where x is the number of prime divisors of N, in each case counted according to their multiplicity. By using a large number of stages, these designs achieve a far greater combinatorial efficiency than has been attained heretofore.
TCP PACKET TRACE ANALYSIS (1991)

Examination of a trace of packets collected from the network is often the only method available for diagnosing protocol performance problems in computer networks. This thesis explores the use of packet traces to diagnose performance problems of the transport protocol TCP. Unfortunately, manual examination of these traces can be so tedious that effective analysis is not possible. The primary contribution of this thesis is a graphical method of displaying the packet trace which greatly reduce, the tediousness of examining a packet trace. The graphical method is demonstrated by the examination of some packet traces of typical TCP connections. The performance of two different implementations of TCP sending data across a particular network path is compared. Traces many thousands of packets long are used to demonstrate how effectively the graphical method simplifies examination of long complicated traces. In the comparison of the two TCP implementations, the burstiness of the TCP transmitter appeared to be related to the achieved throughput. A method of quantifying this burstiness is presented and its possible relevance to understanding the performance of TCP is discussed.
Joint Signal-Labeling Optimization for Pragmatic Capacity under Peak-Power Constraint (2010)

In this paper we introduce a variation of simulated annealing algorithm for optimizing two-dimensional constellations with finite number of signals when the objective function is the symmetric capacity. Our method also allows the joint optimization of constellation and binary labeling when the objective function is the pragmatic capacity. The algorithm can be applied with constraints on both the peak-power and the average and peak-power of the constellation. The proposed algorithm does not impose any a-priori geometrical structure on the constellation and labeling. Here we provide results only for the peak-power constraints. For the usual symmetric capacity, optimal constellations depend on the signal to noise ratio and match in several cases the constellations already found in literature (APSK). On the other hand, for the pragmatic capacity several novel labeling-constellation schemes are introduced, showing interesting differences between the two approaches.
A Biocompatible Arginine‐Based Polycation (2010)

Self assembly between cations and anions is ubiquitous throughout nature. Important biological structures such as chromatin often use polyvalent assembly between a polycation and a polyaninon. Biomedical importance of synthetic polycations arises from their affinity to polyanions such as nucleic acid and heparan sulfate. However, the limited biocompatibility of synthetic polycations hampers the realization of their immense potential. By examining biocompatible cationic peptides, we hypothesize that a biocompatible polycation should be biodegradable and made from endogenous cations. We designed an arginine-based biodegradable polycation and demonstrated that it was orders of magnitude more compatible than conventional polycations in vitro and in vivo. This biocompatibility diminishes when L-arginine is substituted with D-arginine or when the biodegradable ester linker changes to a biostable ether linker. We believe this design can lead to many biocompatible polycations that can significantly advance a wide range of applications including controlled release, tissue engineering, biosensing, and medical devices.
Applied numerical linear algebra (1998)

Preface 1. Introduction 2. Linear equation solving 3. Linear least squares problems 4. Nonsymmetric Eigenvalue problems 5. The symmetric Eigenproblem and singular value decomposition 6. Iterative methods for linear systems 7. Iterative methods for Eigenvalue problems Bibliography Index.
A Cephalotaxine Synthesis Founded on a Mechanistically Interesting, Quasi-biomimetic Strategy (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA Cephalotaxine Synthesis Founded on a Mechanistically Interesting, Quasi-biomimetic StrategyXiaodong Lin, Robert W. Kavash, and Patrick S. MarianoCite this: J. Am. Chem. Soc. 1994, 116, 21, 9791–9792Publication Date (Print):October 1, 1994Publication History Published online1 May 2002Published inissue 1 October 1994https://pubs.acs.org/doi/10.1021/ja00100a071https://doi.org/10.1021/ja00100a071research-articleACS PublicationsRequest reuse permissionsArticle Views698Altmetric-Citations30LEARN 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-Alertsclose Get e-Alerts
Synovial microenvironment‐t cell interactions (1988)

Synovitis in rheumatoid arthritis is characterized by infiltration of the synovium by T and B lymphocytes and monocytes, as well as by the proliferation of synovial lining cells, fibroblasts, and endothelial cells. To study synovial cell-T cell interactions in vitro, we established cultures of fibroblast-like synovial cells, and used these cells in a synovial cell-T cell binding assay. Using T cells at various stages of differentiation and activation, we found that human thymocytes and mitogen-activated peripheral blood T cells bound to fibroblast-like synovial cells, whereas fresh peripheral blood T cells did not. Moreover, activated T cells from inflammatory synovial tissue or from synovial fluid also bound to fibroblast-like synovial cells cultured in vivo. Antibodies against certain epitopes of the T cell CD2 (35.1) and synovial cell lymphocyte function-associated antigen-3 (LFA-3) (TS2/9) molecules inhibited synovial cell-thymocyte binding. However, these same anti-CD2 and anti-LFA-3 antibodies only partially inhibited synovial cell binding to activated normal peripheral blood T cells. Moreover, T cells from inflammatory synovium from rheumatoid arthritis and psoriatic arthritis patients also bound to synovial cells in vitro. These findings demonstrate that fibroblast-like synovial cells are capable of binding to human T cells in vitro, and suggest that during the course of inflammatory synovitis, synovial fibroblast-T cell interactions may occur in vivo.
Synthesis and Evaluation of Carbamate Prodrugs of a Phenolic Compound (2007)

A series of carbamates of the phenolic compound 1 were prepared and evaluated in vivo as its prodrug. Each carbamate was orally administered to rats, and plasma concentrations of the parent compound 1 were measured with the passage of time. We judged which carbamate was suitable for the prodrug of 1 from both the AUC value of 1 and absence of the carbamate in plasma. The AUC value of 1 after oral administration of 2b was approximately 40-fold higher than that for an administration of 1, and the bioconversion from 2b to 1 was excellent. As a whole, di-substituted carbamates resulted in higher plasma concentrations of 1 than did mono-substituted ones. However di-substituted carbamates were almost always detected in plasma. As a result, we found that the ethycarbamoyl derivative 2b demonstrates the best prodrug property in this series.
Development of Carbon Nanotube-Based Sensors—A Review (2007)

Carbon nanotubes (CNTs) have shown great promise as sensing elements in nanoelectromechanical sensors. In this review paper, we discuss the electrical, mechanical, and electromechanical properties of CNTs that are used in such applications. This investigation indicates which nanotube properties should be carefully considered when designing nanotube-based sensors. We then present the primary techniques that have been used for the integration of nanotubes into devices and proceed to give a description of sensors that have been developed using CNTs as active sensing elements