gebhart/patrepeval huggingface dataset:
Lipin Expression Preceding Peroxisome Proliferator-activated Receptor-γ Is Critical for Adipogenesis in Vivo and in Vitro (2004)

We recently identified mutations in the lipin gene, Lpin1, as the cause of lipodystrophy in the fatty liver dystrophy (fld) mouse. Here we identify impaired adipocyte differentiation as the basis for lipodystrophy in lipin-deficient mice and demonstrate that lipin is required for normal induction of the adipogenic gene transcription program. We found that the reduced adiposity in chow fed fld mice and resistance to obesity in fld mice fed a high-fat diet is associated with reduced adipogenic gene expression. Using primary mouse embryonic fibroblasts isolated from fld mice, we confirmed that lipin deficiency prevents normal lipid accumulation and induction of key adipogenic genes, including peroxisome proliferator-activated receptor (PPAR)gamma and CCAAT enhancer-binding protein (C/EBP)alpha. However, our previous studies of daily gene expression in differentiating 3T3-L1 preadipocytes indicated that lipin expression is undetectable until about day 3 of differentiation, at a point after PPARgamma and C/EBPalpha gene expression is established. This paradox was resolved by examining gene expression at 10-h intervals during 3T3-L1 cell differentiation, leading to detection of transient lipin expression at 10 h into the differentiation program, prior to the induction of PPARgamma and C/EBPalpha. Consistent with a requirement for lipin expression upstream of PPARgamma, differentiation of lipin-deficient mouse embryonic fibroblasts could be rescued by ectopic expression of PPARgamma. Thus, we conclude that lipin expression is required prior to PPARgamma during adipocyte differentiation.
Cationic nanoparticles for cancer therapy (2010)

Cationic polymer-based nanoparticles emerge as a promising group of nanosize carrier systems to the tumor cell level with a wide range of modification and application possibilities.
Involvement of pp60c-src with two major signaling pathways in human breast cancer. (1994)

The phosphotyrosine residues of receptor tyrosine kinases serve as unique binding sites for proteins involved in intracellular signaling, which contain SRC homology 2 (SH2) domains. Since overexpression or activation of the pp60c-src kinase has been reported in a number of human tumors, including primary human breast carcinomas, we examined the interactions of the SH2 and SH3 domains of human SRC with target proteins in human carcinoma cell lines. Glutathione S-transferase fusion proteins containing either the SH2, SH3, or the entire SH3/SH2 region of human SRC were used to affinity purify tyrosine-phosphorylated proteins from human breast carcinoma cell lines. We show here that in human breast carcinoma cell lines, the SRC SH2 domain binds to activated epidermal growth factor receptor (EGFR) and p185HER2/neu. SRC SH2 binding to EGFR was also observed in a nontumorigenic cell line after hormone stimulation. Endogenous pp60c-src was found to tightly associate with tyrosine-phosphorylated EGFR. Association of the SRC SH2 with the EGFR was blocked by tyrosyl phosphopeptides containing the sequences surrounding tyrosine-530, the regulatory site in the SRC C terminus, or sequences surrounding the major sites of autophosphorylation in the EGFR. These results raise the possibility that association of pp60c-src with these receptor tyrosine kinases is an integral part of the signaling events mediated by these receptors and may contribute to malignant transformation.
Potentiation of Ototoxicity by Glutathione Depletion (1988)

The combination of 10 mg/kg ethacrynic acid (ETA) and 100 mg/kg kanamycin (KA) caused neither morphologic damage to the cochlea nor change in the auditory brain stem response of the chinchilla. However, after pretreatment with a single dose of buthionine sulfoximine (BSO; 800 mg/kg intraperitoneally) to reduce intracellular glutathione (gamma-glutamylcysteinylglycine; GSH) levels, the above single administration of ETA and KA resulted in complete deafness and severe morphologic damage. The kidney, which has a rapid GSH turnover and is therefore especially susceptible to GSH depletion by BSO, also demonstrated severe damage after this treatment. A similar rapid turnover of GSH and resulting limited capacity to detoxify reactive metabolites and free radicals may determine cochlear and renal vulnerability to this toxicity. These findings may explain the clinical observations of enhanced ototoxicity in patients administered amino-glycoside antibiotics concomitantly with loop diuretics.
Highly Emissive Nano Rod-in-Rod Heterostructures with Strong Linear Polarization (2011)

We report the synthesis of CdSe/CdS rod in rod core/shell heterostructures. These rods, synthesized using a seeded-growth approach, show narrow distributions of rod diameters and lengths and exhibit high emission quantum efficiencies and highly polarized emission. The degree of polarization is controlled by the inner core rod dimensions, and it is equal or up to 1.5 times higher than the polarization of equivalent sphere in rod systems. Using the method of photoselection we measure the polarization anisotropy at different excitation wavelengths and study the interplay between electronic contribution and dielectric effects in determining the absorption and emission polarization.
RNA Aptamers That Bind to and Inhibit the Ribosome-inactivating Protein, Pepocin (2000)

Pepocin, isolated from Cucurbita pepo, is a ribosome-inactivating protein (RIP). RIPs site-specifically recognize and depurinate an adenosine at position 4324 in rat 28 S rRNA, rendering the ribosome incapable of interacting with essential elongation factors. Aptamers that target pepocin were isolated from a degenerate RNA pool by in vitro selection. A conserved hairpin motif, quite different from the sequence of the toxin-substrate domain in rat 28 S rRNA, was identified in the aptamer sequences. The aptamers selectively bind to pepocin with dissociation constants between 20 and 30 nM and inhibit the N-glycosidase activity of pepocin on rat liver 28 S rRNA. Competitive binding experiments using aptamer variants suggest that the conserved hairpin region in the anti-pepocin aptamer binds near the catalytic site on pepocin and prevents the interaction of pepocin and 28 S rRNA. Anti-RIP aptamers have potential use in diagnostic systems for the detection of pepocin or could be used as therapy to prevent the action of pepocin in mammalian cells.
Resolved Motion Rate Control of Manipulators and Human Prostheses (1969)

The kinematics of remote manipulators and human prostheses is analyzed for the purpose of deriving resolved motion rate control. That is, the operator is enabled to call for the desired hand motion directly along axes relevant to the task environment. The approach suggests solutions to problems of coordination, motion under task constraints, and appreciation of forces encountered by the controlled hand.
1,25 Dihydroxyvitamin D Amplifies Type A Natriuretic Peptide Receptor Expression and Activity in Target Cells (2004)

1,25 dihydroxyvitamin D (VD) has been shown to exert a number of beneficial effects on cardiovascular function, including reduction in BP and inhibition of cardiac hypertrophy. In an effort to identify a possible mechanistic link between VD and these salutary effects, the role of VD in controlling the activity and expression of the type A natriuretic peptide receptor (NPR-A), a receptor that signals reductions in BP and suppression of cellular growth in the myocardium and vascular wall, was investigated. VD, as well as the nonhypercalcemic analogue RO-25-6760, increased NPR-A-dependent cyclic guanosine monophosphate production and NPR-A gene expression in cultured rat aortic smooth muscle cells. The increase in NPR-A expression was associated with an increase in NPR-A gene promoter activity that was critically dependent on the presence of a functional VD receptor response element located approximately 495 bp upstream from the transcription start site of the gene. This element was associated with the VD receptor/retinoid X receptor complex in vitro. Mutation of this element resulted in complete elimination of the VD-dependent induction of the NPR-A gene promoter but did not affect osmotic stimulation of the promoter. Treatment of rats with RO-25-6760 for 7 d increased the atrial natriuretic peptide-dependent excretion of sodium and cyclic guanosine monophosphate without affecting mean arterial BP or plasma calcium levels. This was associated with a twofold increase in NPR-A mRNA levels in the inner medulla. Amplification of NPR-A activity represents a plausible mechanism to account for at least some of the beneficial effects that VD exerts on cardiovascular function.
OX40:OX40L Axis: Emerging Targets for Immunotherapy of Human Disease (2006)

Recent advances in our understanding of the mechanisms through which T cells are activated have led to new therapeutic approaches in the treatment of immunological disorders. An emerging target for selective immune intervention has been the manipulation of T cell costimulatory pathways. Impressive results in animal models have shown that the tumor-necrosis-factor receptor (TNFR) family member, OX40 (CD134), and its binding partner OX40L, are key costimulatory molecules involved in the regulation of many T cell mediated immune disorders. In this review we will highlight these new findings with a particular emphasis on their potential implications for immunotherapy of human disease.
Experimental demonstration of an optical phased array antenna for laser space communications (1994)

The feasibility of an optical phased array antenna applicable for spaceborne laser communications was experimentally demonstrated. Heterodyne optical phase-locked loops provide for a defined phase relationship between the collimated output beams of three single-mode fibers. In the far field the beams interfere with a measured efficiency of 99%. The main lobe of the interference pattern can be moved by phase shifting the subaperture output beams. The setup permitted agile beam steering within an angular range of 1 mr and a response time of 0.7 ms. We propose an operational optical phased array antenna fed by seven lasers, featuring high transmit power and redundance.
A new method of synthesis of fluorescently labelled oligonucleotides and their application in DNA sequencing (1997)

A new approach to the chemical synthesis of oligodeoxynucleotides bearing reporter functional groups at base residues of 3'-end nucleosides is reported. Applications of the 3'-end fluorescently labelled primers for automated DNA sequencing are shown.
All-Polymer Field-Effect Transistor Realized by Printing Techniques (1994)

A field-effect transistor has been fabricated from polymer materials by printing techniques. The device characteristics, which show high current output, are insensitive to mechanical treatments such as bending or twisting. This all-organic flexible device, realized with mild techniques, opens the way for large-area, low-cost plastic electronics.
Codon-Optimized Bacterial Genes Improve l -Arabinose Fermentation in Recombinant Saccharomyces cerevisiae (2008)

Bioethanol produced by microbial fermentations of plant biomass hydrolysates consisting of hexose and pentose mixtures is an excellent alternative to fossil transportation fuels. However, the yeast Saccharomyces cerevisiae, commonly used in bioethanol production, can utilize pentose sugars like l-arabinose or d-xylose only after heterologous expression of corresponding metabolic pathways from other organisms. Here we report the improvement of a bacterial l-arabinose utilization pathway consisting of l-arabinose isomerase from Bacillus subtilis and l-ribulokinase and l-ribulose-5-P 4-epimerase from Escherichia coli after expression of the corresponding genes in S. cerevisiae. l-Arabinose isomerase from B. subtilis turned out to be the limiting step for growth on l-arabinose as the sole carbon source. The corresponding enzyme could be effectively replaced by the enzyme from Bacillus licheniformis, leading to a considerably decreased lag phase. Subsequently, the codon usage of all the genes involved in the l-arabinose pathway was adapted to that of the highly expressed genes encoding glycolytic enzymes in S. cerevisiae. Yeast transformants expressing the codon-optimized genes showed strongly improved l-arabinose conversion rates. With this rational approach, the ethanol production rate from l-arabinose could be increased more than 2.5-fold from 0.014 g ethanol h(-1) (g dry weight)(-1) to 0.036 g ethanol h(-1) (g dry weight)(-1) and the ethanol yield could be increased from 0.24 g ethanol (g consumed l-arabinose)(-1) to 0.39 g ethanol (g consumed l-arabinose)(-1). These improvements make up a new starting point for the construction of more-efficient industrial l-arabinose-fermenting yeast strains by evolutionary engineering.
Efficient, specific interstrand cross-linking of double-stranded DNA by a chlorambucil-modified, triplex-forming oligonucleotide (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEfficient, specific interstrand cross-linking of double-stranded DNA by a chlorambucil-modified, triplex-forming oligonucleotideIgor V. Kutyavin, Howard B. Gamper, Alexander A. Gall, and Rich B. Meyer Jr.Cite this: J. Am. Chem. Soc. 1993, 115, 20, 9303–9304Publication Date (Print):October 1, 1993Publication History Published online1 May 2002Published inissue 1 October 1993https://pubs.acs.org/doi/10.1021/ja00073a062https://doi.org/10.1021/ja00073a062research-articleACS PublicationsRequest reuse permissionsArticle Views181Altmetric-Citations32LEARN 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
Deep learning for single-molecule science (2017)

Exploring and making predictions based on single-molecule data can be challenging, not only due to the sheer size of the datasets, but also because a priori knowledge about the signal characteristics is typically limited and poor signal-to-noise ratio. For example, hypothesis-driven data exploration, informed by an expectation of the signal characteristics, can lead to interpretation bias or loss of information. Equally, even when the different data categories are known, e.g., the four bases in DNA sequencing, it is often difficult to know how to make best use of the available information content. The latest developments in machine learning (ML), so-called deep learning (DL) offer interesting, new avenues to address such challenges. In some applications, such as speech and image recognition, DL has been able to outperform conventional ML strategies and even human performance. However, to date DL has not been applied much in single-molecule science, presumably in part because relatively little is known about the 'internal workings' of such DL tools within single-molecule science as a field. In this Tutorial, we make an attempt to illustrate in a step-by-step guide how one of those, a convolutional neural network (CNN), may be used for base calling in DNA sequencing applications. We compare it with a SVM as a more conventional ML method, and discuss some of the strengths and weaknesses of the approach. In particular, a 'deep' neural network has many features of a 'black box', which has important implications on how we look at and interpret data.
Effects of 6 Weeks of Therapy with Oral Doses of ICI 204,219, a Leukotriene D4 Receptor Antagonist, in Subjects with Bronchial Asthma. ACCOLATE Asthma Trialists Group (1994)

The efficacy of 6 wk of therapy with oral ICI 204,219, a selective leukotriene D4 (LTD4) receptor antagonist, was evaluated in subjects with moderate asthma during a multicenter, double-blind, randomized, placebo-controlled, dose-ranging study. Subjects who entered the trial had been chronically treated for asthma with beta agonist alone or in combination with theophylline. Subjects were randomized to treatment with twice daily doses of ICI 204,219 (5, 10, or 20 mg) or placebo if they had an FEV1 between 40 and 75% of predicted values without bronchodilator therapy and a daytime asthma score > 10 (range 0 to 21 per wk) for 7 consecutive d. Efficacy was evaluated from the results of symptom assessments, pulmonary function tests, and rescue medication use. Of 276 subjects randomized to treatment, 266 (10 mg, n = 66; 20 mg, n = 67; 40 mg, n = 67; placebo, n = 66) were analyzed for efficacy. Diary card assessments showed that treatment with increasing doses of ICI 204,219 linearly improved five efficacy criteria without increasing the number or severity of adverse events. The 40 mg dose was more effective than placebo (p < 0.05) in reducing nighttime awakenings, first morning asthma symptoms, the daytime asthma score, and albuterol use and in increasing evening peak expiratory flow (PEF) rates as well as FEV1. Compared with baseline measurements, the 40 mg dose decreased awakenings by 46%, albuterol use by 30%, and daytime symptoms by 26% and increased FEV1 by 11%. ICI 204,219 improves objective and subjective measures of asthma severity in moderately ill asthmatic subjects and may provide a new treatment option for the disease.
Role of Epithelial Cells in Inflammatory Bowel Disease (2009)

A single layer of intestinal epithelial cells (IECs) forms the barrier between the largest accumulation of microbes in the body and the host itself. Functional insight into the biology of IECs has revealed a profound impact of IEC function on mucosal homeostasis and immune function. Moreover, genome-wide association studies and candidate gene studies have substantially expanded our insight into the genetic underpinning of human inflammatory bowel disease. Several pathways regulated by products of genes that are genetically associated with inflammatory bowel disease, like the endoplasmic stress response (XBP1), autophagy (ATG16L1), and innate immune pathways (NOD2) profoundly affect IEC function, in particular Paneth cells. Paneth cells reside at the base of small intestinal crypts and secrete abundant amounts of antimicrobial peptides, and are thereby considered to substantially affect the composition of the microbial flora. Further evidence from the study of NFκB signaling in IECs revealed important insights into how IECs regulate mucosal innate and adaptive immunity via cross-talk with dendritic cells, macrophages and CD4+ T cells. These studies indicate that IECs may play a profound role in regulating the interaction between commensal and infectious microbes of the intestinal tract and the host, with consequent implications for infectious and inflammatory diseases of the gastrointestinal tract.
The β1,3-Galactosyltransferase β3GalT-V Is a Stage-specific Embryonic Antigen-3 (SSEA-3) Synthase (2000)

We have previously reported the molecular cloning of beta1, 3-galactosyltransferase-V (beta3GalT-V), which catalyzes the transfer of Gal to GlcNAc-based acceptors with a preference for the core3 O-linked glycan GlcNAc(beta1,3)GalNAc structure. Further characterization indicated that the recombinant beta3GalT-V enzyme expressed in Sf9 insect cells also utilized the glycolipid Lc3Cer as an efficient acceptor. Surprisingly, we also found that beta3GalT-V catalyzes the transfer of Gal to the terminal GalNAc unit of the globoside Gb4, thereby synthesizing the glycolipid Gb5, also known as the stage-specific embryonic antigen-3 (SSEA-3). The SSEA-3 synthase activity of beta3GalT-V was confirmed in vivo by stable expression of the human beta3GalT-V gene in F9 mouse teratocarcinoma cells, as detected with the monoclonal antibody MC-631 by flow cytometry analysis and immunostaining of extracted glycolipids. The biological relation between SSEA-3 formation and beta3GalT-V was further documented by showing that F9 cells treated with the differentiation-inducing agent retinoic acid induced the expression of both the SSEA-3 epitope and the endogenous mouse beta3GalT-V gene. This study represents the first example of a glycosyltransferase, which utilizes two kinds of sugar acceptor substrates without requiring any additional modifier molecule.
Encountering the mandala: the mental and political architectures of dependency (2001)

Extract: From basic atomic and cellular structure to snowflakes, eyes, flowers, spider webs, tree rings to the solar system and spiral nebulae, mandalas abound in nature. The basic concept of the mandala, a circle and its centre, is also culturally abundant: though most notable within the Tibetan Mahayana tradition, mandalas are significant for the religious and secular lives of many peoples. They have for instance, long been identified in Native American art and medical practice (medicine wheels), particularly the sand mandalas of the Navajo.
Chemokine Protocols (2000)

In the past decade research has established the biological importance of chemokines: they play a major role in leukocyte trafficking, in the recruitment of leukocytes to inflammatory sites, and are coreceptors along with CD4 for HIV cell entry. In Chemokine Protocols, expert investigators describe in detail important techniques usedchemokine biology. Covering both ligands and receptors, these readily reproducible methods cover all aspects of chemokine research, ranging from the cloning and characterization of chemokines and their receptors, through the use of animal models to study chemokine function in vivo. Each method also includes relevant background information, as well as providing a useful bibliography that renders the study of chemokines accessible at all levels of experience. Comprehensive and highly practical, Chemokine Protocols offers experimental and clinical chemokine researchers today's gold-standard collection of proven methods for analyzing this biologically ubiquitous and important class of proteins
The production of viral vectors designed to express large and difficult to express transgenes within neurons (2015)

We determined that viral packaging limit, transgene promoter and the presence of an intron within the transgene were all important factors that contributed to being able to successfully develop viral vectors designed to deliver and express GluN2 transgenes in a neuron specific manner. Because these vectors have been optimized to accommodate large open reading frames and in some cases contain an intron to facilitate expression of difficult to express transgenes, these viral vectors likely could be useful for delivering and expressing many large or difficult to express transgenes in a neuron specific manner.
DAnTE: a statistical tool for quantitative analysis of -omics data (2008)

An example dataset with instructions on how to perform a series of analysis steps is available at http://omics.pnl.gov/software/