gebhart/patrepeval huggingface dataset:
Stochastic mRNA Synthesis in Mammalian Cells (2006)

Individual cells in genetically homogeneous populations have been found to express different numbers of molecules of specific proteins. We investigated the origins of these variations in mammalian cells by counting individual molecules of mRNA produced from a reporter gene that was stably integrated into the cell's genome. We found that there are massive variations in the number of mRNA molecules present in each cell. These variations occur because mRNAs are synthesized in short but intense bursts of transcription beginning when the gene transitions from an inactive to an active state and ending when they transition back to the inactive state. We show that these transitions are intrinsically random and not due to global, extrinsic factors such as the levels of transcriptional activators. Moreover, the gene activation causes burst-like expression of all genes within a wider genomic locus. We further found that bursts are also exhibited in the synthesis of natural genes. The bursts of mRNA expression can be buffered at the protein level by slow protein degradation rates. A stochastic model of gene activation and inactivation was developed to explain the statistical properties of the bursts. The model showed that increasing the level of transcription factors increases the average size of the bursts rather than their frequency. These results demonstrate that gene expression in mammalian cells is subject to large, intrinsically random fluctuations and raise questions about how cells are able to function in the face of such noise.
Humoral and Cellular Immune Responses to Enolase after Alimentary Tract Colonization or Intravenous Immunization with Candida albicans (1994)

Immune responses to defined antigens of the AIDS opportunistic pathogen Candida albicans that arise as a consequence of alimentary tract colonization or induced candidemia were assessed. Lymphocyte activation and antibody production to the abundant immunodominant antigen enolase were evident in germfree mice colonized with C. albicans. Lymphocytes from colonized or intravenously challenged mice responded to a recombinant C. albicans enolase fusion protein (EFP). The responses to EFP were significantly higher than the responses to a control protein, glutathione S-transferase. In immunoblotting experiments, enolase was the immunodominant humoral immunogen in these mice. These results demonstrate that enolase stimulates cellular and humoral responses and that specific immune responses to enolase are sensitive indicators of the presence of proliferating C. albicans in mice.
Direct Quantitation of Peptide Mixtures without Standards Using Clusters Formed by Electrospray Ionization Mass Spectrometry (2009)

In electrospray ionization mass spectrometry, ion abundances depend on a number of different factors, including analyte surface activity, competition between analytes for charge, analyte concentration, as well as instrumental factors, including mass-dependent ion transmission and detection. Here, a novel method for obtaining quantitative information about solution-phase concentrations of peptide mixtures is described and demonstrated for five different peptide mixtures with relative concentrations ranging from 0.05% to 50%. In this method, the abundances of large clusters containing anywhere from 0 to 13 impurity molecules are measured and directly related to the relative solution-phase concentration of the peptides. For clusters containing approximately 15 or more peptides, the composition of the clusters approaches the statistical value indicating that these clusters are formed nonspecifically and that any differences in ion detection or ionization efficiency are negligible at these large cluster sizes. This method is accurate to within approximately 20% or better, even when the relative ion intensities of the protonated monomers can differ by over an order of magnitude compared to their solution-phase concentrations. Although less accurate than other quantitation methods that employ internal standards, this method does have the key advantages of speed, simplicity, and the ability to quantitate components in solution even when the identities of the components are unknown.
Microenvironmental influences on human B-cell development (2000)

Summary: Mammalian B-cell development can be viewed as a developmental performance with several acts. The acts are represented by checkpoints centered around commitment to the B-lineage and functional Ig gene rearrangement – culminating in expression of the pre-B-cell receptor (pre-BCR) and the BCR. Progression of cells through these checkpoints is profoundly influenced by the fetal liver and adult bone marrow (BM) stromal cell microenvironments. Our laboratory has developed a model of human B-cell development that utilizes freshly isolated/non-transformed human BM stromal cells as an in vitro microenvironment. Human CD34+ hematopoietic stem cells plated in this human BM stromal cell microenvironment commit to the B lineage and progress through the pre-BCR and BCR checkpoints. This human BM stromal cell microenvironment also provides survival signals that prevent apoptosis in human B-lineage cells. Human B-lineage cells exhibit differential expression of Notch receptors and human BM stromal cells express the Notch ligand Jagged-1. These results suggest a potential role for Notch in regulating B-lineage commitment and/or progression through the pre-BCR and BCR checkpoints.
Processing techniques for deoxyribonucleic acid: Biopolymer for photonics applications (2005)

Marine-based deoxyribonucleic acid (DNA), purified from waste products of the Japanese fishing industry, has recently become a material of interest in photonics applications. Using highly purified DNA, unique processing techniques developed specifically to transform the purified DNA into a biopolymer suitable for optical device fabrication are reported.
Constitutively activated phosphatidylinositol-3 kinase (PI-3K) is involved in the defect of apoptosis in B-CLL: association with protein kinase Cδ (2002)

In the present study we analyzed the role of phophatidylinositol-3 kinase (PI-3K) in B chronic lymphocytic leukemia (B-CLL) cells. PI-3K is activated by many stimuli and is linked to several different signaling pathways. We demonstrated that inhibition of PI-3K by a specific inhibitor, LY294002, induced apoptosis in B-CLL cells in vitro. This effect was specific for the inhibition of PI-3K because inhibition of other signaling pathways such as extracellular signaling-regulated kinase (ERK), p38, or p70S6 kinase did not affect spontaneous apoptosis. Furthermore, PI-3K was constitutively activated in freshly isolated B-CLL cells. Corresponding to enhanced apoptosis, LY294002 down-regulated expression of the antiapoptotic proteins X-linked inhibitor of apoptosis protein (XIAP) and Mcl-1. Next, we investigated which factors downstream of PI-3K were activated in B-CLL cells. We demonstrated that protein kinase B/Akt is expressed in all tested CLL samples but no activation of Akt was detected. In contrast, we observed a constitutive activation of protein kinase Cdelta (PKCdelta) in freshly isolated B-CLL cells. PKCdelta is linked to PI-3K and is phosphorylated at Thr505 in response to PI-3K activation. We further demonstrated that tyrosine phosphorylation and activity of PKCdelta were dependent on PI-3K activity in B-CLL cells. Inhibition of PKCdelta by the specific inhibitor Rottlerin strikingly enhanced apoptosis. In contrast, peripheral blood B cells of healthy donors were resistant to inhibition of PI-3K or PKCdelta. We conclude that activated PI-3K might be important in the pathogenesis of B-CLL, and survival signals might be mediated via PKCdelta. Therefore, inhibition of PI-3K or PKCdelta may be an innovative approach to treat B-CLL.
Anaphylactic Reactions after Gamma Globulin Administration in Patients with Hypogammaglobulinemia (1986)

VYAS and co-workers1 were the first to identify anti-IgA antibodies as the cause of anaphylactic reactions to human blood products in patients with selective IgA deficiency. Other reports of anaphylaxis due to anti-IgA antibodies soon followed,2 3 4 5 6 7 8 9 10 11 12 13 including several reports of anaphylactic reactions in patients with common variable immunodeficiency.3 4 5 6 7 8 , 11 Although such patients have severe defects in antibody production, they often retain the ability to produce autoantibodies. Gamma globulin replacement is essential in the management of hypogammaglobulinemia,6 in contrast to selective IgA deficiency. Therefore, it is important to find ways to circumvent these life-threatening anaphylactic reactions and to provide adequate replacement therapy. . . .
CD4+ T lymphocytes play a critical role in antibody production and tumor immunity against simian virus 40 large tumor antigen. (2003)

The role of CD4+ T lymphocytes in antitumor immunity has been largely attributed to providing signals required for the priming of MHC class I-restricted CD8+ cytotoxic T lymphocytes, and CD8+ cytotoxic T lymphocytes are thought to serve as the predominant mediators of tumor killing in vivo. We decided to evaluate the role of T lymphocyte subsets in tumor immunity induced by recombinant SV40 large tumor antigen (Tag) within an experimental murine pulmonary metastasis model of SV40 Tag-expressing tumors. Studies in BALB/c mice used in vivo depletion of either CD4+ or CD8+ T cells in the induction phase of the immune response to SV40 Tag. These studies indicate that CD4+ T cells but not CD8+ T cells were critical in the production of antibodies to SV40 Tag and in tumor immunity as the result of recombinant SV40 Tag immunization. On the basis of the predominance of the IgG1 isotype in the antibody response to SV40 Tag immunization, Th2 type CD4+ T cells appeared to be involved. SV40 Tag immunization was not as effective in the induction of tumor immunity in therapeutic modalities when compared with the prophylactic setting. Our results suggest that CD4+ T cells, along with antibody responses, play a role in the induction of tumor immunity to a viral-encoded tumor antigen.
Cyp26 enzymes function in endoderm to regulate pancreatic field size (2009)

The control of organ size and position relies, at least in part, upon appropriate regulation of the signals that specify organ progenitor fields. Pancreatic cell fates are specified by retinoic acid (RA), and proper size and localization of the pancreatic field are dependent on tight control of RA signaling. Here we show that the RA-degrading Cyp26 enzymes play a critical role in defining the normal anterior limit of the pancreatic field. Disruption of Cyp26 function causes a dramatic expansion of pancreatic cell types toward the anterior of the embryo. The cyp26a1 gene is expressed in the anterior trunk endoderm at developmental stages when RA is signaling to specify pancreas, and analysis of cyp26a1/giraffe (gir) mutant zebrafish embryos confirms that cyp26a1 plays the primary role in setting the anterior limit of the pancreas. Analysis of the gir mutants further reveals that cyp26b1 and cyp26c1 function redundantly to partially compensate for loss of Cyp26a1 function. We used cell transplantation to determine that Cyp26a1 functions directly in endoderm to modulate RA signaling and limit the pancreatic field. Taken together with our finding that endodermal expression of cyp26 genes is subject to positive regulation by RA, our data reveal a feedback loop within the endoderm. Such feedback can maintain consistent levels of RA signaling, despite environmental fluctuations in RA concentration, thus ensuring a consistent size and location of the pancreatic field.
Nerve Growth Factor Induces Apoptosis in Human Medulloblastoma Cell Lines that Express TrkA Receptors (1997)

Neurotrophins act through their cognate receptors to promote the differentiation and/or survival of neuronal progenitor cells, immature neurons, and other cells. Here, we examined the effects of nerve growth factor (NGF) and its cognate receptor (Trk or TrkA) on the survival of a common childhood brain tumor, i.e., medulloblastoma, a tumor that resembles CNS neuroepithelial progenitor cells. To do this, we engineered two human medulloblastoma cell lines (i.e., D283MED and DAOY cells) to express human TrkA using a retroviral expression vector. Surprisingly, NGF-treated medulloblastoma cells expressing the TrkA receptor (D283trk and DAOYtrk cells) grown in the presence or absence of serum underwent massive apoptosis, but similar treatment did not induce apoptosis in wild-type uninfected cells, cells expressing an empty vector, or cells expressing the TrkC receptor. Furthermore, D283MED cells engineered to express the human p75 NGF receptor (D283p75) also did not undergo apoptosis. Significantly, NGF-induced apoptosis in D283trk and DAOYtrk cells can be inhibited by anti-NGF antibodies and by K-252a, an inhibitor of TrkA tyrosine phosphorylation and mimicked by high concentrations of NT3. Because NGF treatment primarily eliminated D283trk cells from the S phase of the cell cycle, this form of NGF-mediated apoptosis is cell cycle-dependent. These findings suggest that a NGF/TrkA signal transduction pathway could activate apoptotic cell death programs in CNS neuroepithelial progenitor cells and in childhood brain tumors.
Searching the workplace web (2003)

The social impact from the World Wide Web cannot be underestimated, but technologies used to build the Web are also revolutionizing the sharing of business and government information within intranets. In many ways the lessons learned from the Internet carry over directly to intranets, but others do not apply. In particular, the social forces that guide the development of intranets are quite different, and the determination of a "good answer" for intranet search is quite different than on the Internet. In this paper we study the problem of intranet search. Our approach focuses on the use of rank aggregation, and allows us to examine the effects of different heuristics on ranking of search results.
Fumarates for the treatment of multiple sclerosis: potential mechanisms of action and clinical studies (2008)

All licensed disease-modifying drugs for the treatment of relapsing-remitting multiple sclerosis (MS) only display partial efficacy and hitherto require parenteral administration. Thus, there is a high demand for innovative and at the same time orally available MS therapeutics. Fumaric acids and their esters (FAE) may represent such a new class of compounds. FAE display immunomodulatory properties and may also exert neuroprotective effects, as shown in vitro as well as in experimental models of MS. A first Phase II study with the new, modified FAE BG00012/FAG-201 (BG-12) in relapsing-remitting MS revealed significant effects on MRI parameters such as gadolinium-enhancing lesions, T1 hypointense lesions and T2 lesion load after 24 weeks of treatment. The trial also underlined the safety and good tolerability of FAE that are already in clinical use for the systemic treatment of severe psoriasis. Presently, two Phase III studies are ongoing to investigate the clinical long-term efficacy of BG-12. In summary, FAE are potential candidates that may open a new therapeutic option for relapsing-remitting MS in the near future.
The ntrB and ntrC Genes Are Involved in the Regulation of Poly-3-Hydroxybutyrate Biosynthesis by Ammonia in Azospirillum brasilense Sp7 (2000)

Azospirillum brasilense Sp7 and its ntrA (rpoN), ntrBC, and ntrC mutants have been evaluated for their capabilities of poly-3-hydroxybutyrate (PHB) accumulation in media with high and low ammonia concentrations. It was observed that the ntrBC and ntrC mutants can produce PHB in both low- and high-C/N-ratio media, while no significant PHB production was observed for the wild type or the ntrA mutant in low-C/N-ratio media. Further investigation by fermentation analysis indicated that the ntrBC and ntrC mutants were able to grow and accumulate PHB simultaneously in the presence of a high concentration of ammonia in the medium, while little PHB was produced in the wild type and ntrA (rpoN) mutant during active growth phase. These results provide the first genetic evidence that the ntrB and ntrC genes are involved in the regulation of PHB synthesis by ammonia in A. brasilense Sp7.
Transforming Growth Factor β-activated Kinase 1 (TAK1) Kinase Adaptor, TAK1-binding Protein 2, Plays Dual Roles in TAK1 Signaling by Recruiting Both an Activator and an Inhibitor of TAK1 Kinase in Tumor Necrosis Factor Signaling Pathway (2009)

Transforming growth factor beta-activated kinase 1 (TAK1) kinase is an indispensable signaling intermediate in tumor necrosis factor (TNF), interleukin 1, and Toll-like receptor signaling pathways. TAK1-binding protein 2 (TAB2) and its closely related protein, TAB3, are binding partners of TAK1 and have previously been identified as adaptors of TAK1 that recruit TAK1 to a TNF receptor signaling complex. TAB2 and TAB3 redundantly mediate activation of TAK1. In this study, we investigated the role of TAB2 by analyzing fibroblasts having targeted deletion of the tab2 gene. In TAB2-deficient fibroblasts, TAK1 was associated with TAB3 and was activated following TNF stimulation. However, TAB2-deficient fibroblasts displayed a significantly prolonged activation of TAK1 compared with wild type control cells. This suggests that TAB2 mediates deactivation of TAK1. We found that a TAK1-negative regulator, protein phosphatase 6 (PP6), was recruited to the TAK1 complex in wild type but not in TAB2-deficient fibroblasts. Furthermore, we demonstrated that both PP6 and TAB2 interacted with the polyubiquitin chains and this interaction mediated the assembly with TAK1. Our results indicate that TAB2 not only activates TAK1 but also plays an essential role in the deactivation of TAK1 by recruiting PP6 through a polyubiquitin chain-dependent mechanism.
Update on Progressive Familial Intrahepatic Cholestasis (2008)

Three distinct forms of familial intrahepatic cholestasis are the result of mutations in the ATP8B1, ABCB11, and ABCB4 genes. The pathophysiologies of the latter 2 of these diseases are well characterized and are the result of abnormalities in canalicular excretion of bile acids and phospholipids, respectively. The molecular pathophysiology of the systemic disease associated with mutations in ATP8B1 remains unclear. In all of these diseases, wide variations in clinical phenotypes have been observed. The variability can be ascribed at least in part to predicted genotype:phenotype correlations. Disease- and genotype-specific prognoses and therapeutic approaches may exist, although much more information needs to be ascertained before clinicians can confidently make decisions based on genetic information.
Bactericidal activity of clinically used local anesthetics on Staphylococcus aureus. (1996)

Antimicrobial activity was observed shortly after exposure of S. aureus to local anesthetics and appeared to be bactericidal rather than bacteriostatic. However, the observed bactericidal activity, although it developed rapidly, may be insufficient to account for the low incidence of epidural infection related to epidural cannulation.
Systemic anaphylaxis immediately following delayed hypersensitivity skin tests. (1982)

Delayed hypersensitivity skin tests are performed frequently for other than primary immunologic disorders. Systemic anaphylaxis occurred during delayed hypersensitivity skin testing on a healthy, non-atopic individual. This reaction appeared to be IgE mediated. Anaphylactic recovery sets must be readily available whenever such testing is performed.
Effects of 2&prime;-&lt;italic&gt;O&lt;/italic&gt;-methyl nucleotide on ligation capability of T4 DNA ligase (2014)

To further understand the ligation mechanism, effects of 2'-O-methyl nucleotide (2'-OMeN) on the T4 DNA ligation efficiency were investigated. Fluorescence resonance energy transfer assay was used to monitor the nick-joining process by T4 DNA ligase. Results showed that substitutions at 5'- and 3'-ends of the nick decreased the ligation efficiency by 48.7% ± 6.7% and 70.6% ± 4.0%, respectively. Substitutions at both 5'- and 3'-ends decreased the ligation efficiency by 76.6% ± 1.3%. Corresponding kinetic parameters, Vmax, Km, and kcat, have been determined in each case by using the Michaelis-Menten equation. The kinetic data showed that the 2'-OMeN substitutions reduced the maximal initial velocity and increased the Michaelis constant of T4 DNA ligase. Mismatches at 5'- and 3'-ends of the nick have also shown different influences on the ligation. Results here showed that the sugar pucker conformation at 3'-end impairs the ligation efficiency more profoundly than that at 5'-end. Different concentrations of Mg(2+), Ca(2+), K(+), Na(+), and ATP were also demonstrated to affect the T4 DNA ligase activity. These results enriched our knowledge about the effects of 2'-OMeN substitutions on the T4 DNA ligase.
Phthalocyanine-containing polymers (2000)

The optical and electronic properties of the phthalocyanine (Pc) macrocycle make it suitable for a wide range of applications. The enormous diversity of Pc-containing polymers, developed over thirty years of research, offers the prospect of readily processed materials in which covalent linkages can be used to control the ordering and arrangement of the Pc units. This article reviews both the synthesis and study of Pc-containing polymers. The types of polymer are classified by the way in which the macrocycle is incorporated within the macromolecular structure as either network, main-chain or side-chain polymers. In addition, recent work on the incorporation of the Pc macrocycle as polymer end-groups or as the core unit in a number of dendrimers is also described.
A volume conduction antenna for implantable devices (2004)

We have developed a new volume conduction based antenna, called the x-antenna, that can be embedded in, or connected to, various implantable medical devices. This miniature antenna and an associated transceiver establish a wireless two-way data communication link between a wearable computer and implanted sensors/actuators to perform a variety of therapeutic and diagnostic functions within the human body. Our experiments have shown that the x-antenna requires less than one microwatt of energy to perform data communication tasks, more energy-efficient than any other known data communication modality.
Detection of hazardous vapors including mixtures using pattern recognition analysis of responses from surface acoustic wave devices (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDetection of hazardous vapors including mixtures using pattern recognition analysis of responses from surface acoustic wave devicesSusan L. Rose-Pehrsson, Jay W. Grate, David S. Ballantine, and Peter C. JursCite this: Anal. Chem. 1988, 60, 24, 2801–2811Publication Date (Print):December 15, 1988Publication History Published online1 May 2002Published inissue 15 December 1988https://pubs.acs.org/doi/10.1021/ac00175a032https://doi.org/10.1021/ac00175a032research-articleACS PublicationsRequest reuse permissionsArticle Views390Altmetric-Citations120LEARN 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