gebhart/patrepeval huggingface dataset:
PEG-g-poly(GdDTPA-co-l-cystine):  Effect of PEG Chain Length on in Vivo Contrast Enhancement in MRI (2005)

Biodegradable macromolecular Gd(III) complexes, Gd-DTPA cystine copolymers (GDCP), were grafted with PEG of different sizes to modify the physicochemical properties and in vivo MRI contrast enhancement of the agents and to study the effect of PEG chain length on these properties. Three new PEG-grafted biodegradable macromolecular gadolinium(III) complexes were synthesized and characterized as blood pool MRI contrast agents. One of three different lengths of MPEG-NH(2) (MW = 550, 1000, and 2000) was grafted to the backbone of GDCP to yield PEG(n)()-g-poly(GdDTPA-co-l-cystine), PEG(n)()-GDCP. The PEG chain length did not dramatically alter the T(1) relaxivity, r(1), of the modified agents. The MRI enhancement profile of PEG(n)()-GDCP with different PEG sizes was significantly different in mice with respect to both signal intensity and clearance profiles. PEG(2000)-GDCP showed more prominent enhancement in the blood pool for a longer period of time than either PEG(1000)-GDCP or PEG(550)-GDCP. In the kidney, PEG(2000)-GDCP had less enhancement at 2 min than PEG(1000)-GDCP, but both PEG(550)-GDCP and PEG(1000)-GDCP showed a more pronounced signal decay thereafter. The three agents behaved similarly in the liver, as compared to that in the heart. All three agents showed little enhancement in the muscle. Chemical grafting with PEG of different chain lengths is an effective approach to modify the physiochemistry and in vivo contrast enhancement dynamics of the biodegradable macromolecular contrast agents. The novel agents are promising for further clinical development for cardiovascular and cancer MR imaging.
Easy Preparation of (Diacetoxyiodo)arenes from Iodoarenes with Sodium Percarbonate as the Oxidant (2002)

Easy and effective preparations of nearly pure (diacetoxyiodo)arenes, ArI(OAc)2, from iodoarenes, ArI, are reported. In most cases the crude colorless products thus obtained need not be further purified, i.e., by recrystallization. As an example, the PhI(OAc)2 thus prepared was 99% pure (by iodometry).
Novel Interaction Partners of the CD2BP2-GYF Domain (2005)

The GYF domain of CD2BP2 serves as an adapter that recognizes proline-rich sequences in intracellular proteins. Although the T cell adhesion molecule CD2 and the core splicing protein SmB/B' were previously shown to interact with CD2BP2-GYF, we are now using a general approach to identify putative GYF domain target sites within the human proteome. The phage display-derived recognition motif for CD2BP2-GYF is PPG(W/F/Y/M/L). SPOT analysis confirmed that the GYF domain interacts with peptides from human proteins containing the consensus site. Epitope mapping by NMR spectroscopy performed for several peptides revealed a conserved binding surface. A direct interaction of the CD2BP2-GYF domain with the novel protein interaction partners PI31 and NPWBP was verified by yeast two-hybrid analysis.
New Purines and Purine Analogs as Modulators of Multidrug Resistance (1996)

A series of 36 purine and purine analog derivatives have been synthesized and tested for their ability to modulate multidrug resistance in vitro (P388/VCR-20 and KB-A1 cells) and in vivo (P388/VCR leukemia). Compounds were compared to S9788, a triazine derivative which has already shown some activity during phase 1 clinical trials and also a limiting cardiovascular side effect possibly linked to its calcium channel affinity. The fact that active compounds increase adriamycin accumulation in the resistant KB-A1 cells, and not in the sensitive KB-3-1 cells, suggests they act predominantly by inhibiting the P-glycoprotein-catalyzed efflux of cytotoxic agents. No direct relation was found between the affinity for the phenylalkylamine binding site of the calcium channel and in vitro sensitization of resistant cells. In vivo, when administered po in association with vincristine (0.25 mg/kg), five compounds (3, 4, 9, 25, and 26), of very differing calcium channel affinities (Ki from 5 to 560 nM), fully restored (T/V > or = 1.4) the sensitivity of P388/VCR leukemia to vincristine.
Tree View: An application to display phylogenetic trees on personal computers (1996)

TreeView is a simple, easy to use phylogenetic tree viewing utility that runs under both MacOS (on Apple Macintosh computers) and under Microsoft Windows on Intel based computers, the two most common personal computers used by biologists. Some phylogeny programs, such as PAUP (Swofford, 1993) and MacClade (Maddison and Maddison, 1992) already provide excellent tree drawing and printing facilities, however at present these programs are restricted to Apple Macintosh computers. Furthermore, they require the user to load a data set before any trees can be displayed which is inconvenient if the user simply wants to view the trees. More portable programs, such as DRAWGRAM and DRAWTREE in the PHYLIP package (Felsenstein, 1993) can run on both MacOS and Windows computers, but make little, if any use of the graphical interface features available under those operating systems. TreeView runs as a native application on either MacOS or Windows computers, enables the user to use the standard fonts installed on their machine, their printer, and supports the relevant native graphics format (PICT and Windows metafile) for either creating graphics files or pasting pictures to other applications via the clipboard. The program also supports standard file operations, such as 'drag and drop' whereby dragging a file's icon onto the program opens that file. TreeView can read a range of tree file formats (see below) and can display trees in a range of styles (Fig. 1). Additional information, such as edge lengths and internal node labels can also be displayed. The order of the terminal taxa in the tree can be altered, and the tree can be rerooted. If the tree file contains more than one tree the user can view each tree in turn. The program can also save trees in a variety of file formats, so that it can be used to move trees between programs that use different file formats.
Detection of chromosomal translocation t(14;18) within the minor cluster region of bcl-2 by polymerase chain reaction and direct genomic sequencing of the enzymatically amplified DNA in follicular lymphomas (1989)

A majority of t(14;18) translocations have been shown to cluster at one of two sites on chromosome 18, called the major breakpoint region (mbr) or the minor cluster region, (mcr), which map within or flanking the bcl-2 proto-oncogene, respectively. We have determined the nucleotide sequence for a portion of the mcr, and constructed oligonucleotides that were used to perform the polymerase chain reaction (PCR) in conjunction with universal immunoglobulin primers to specifically amplify t(14;18) breakpoints in DNA obtained from follicular lymphomas. Eight of ten breakpoints that were detectable on Southern blots using DNA probes for the mcr could be detected due to specific amplification by the PCR technique using an mcr-specific primer. Direct nucleotide sequencing of the enzymatically amplified DNAs showed that the breakpoints clustered within a 500 nucleotide region, and five occurred within three nucleotides of each other. These data show a remarkable clustering of some t(14;18) breakpoints at a site on chromosome 18, at least a 30-kb distance from the bcl-2 gene. Our findings also indicate that mcr-specific primers may be used in conjunction with previously described mbr-specific primers in a highly sensitive DNA amplification technique to detect a large fraction of t(14;18) breakpoints.
Detection and Characterization of a Vacuolar Protein (VP24) in Anthocyanin-Producing Cells of Sweet Potato in Suspension Culture (1995)

Vacuoles containing large amounts of protein and anthocyanin were isolated and purified from anthocyanin-producing cultured cells of sweet potato (Ipomoea batatas). A 24 kDa protein (VP24), identified as a major protein in the isolated vacuoles, was detected by SDS-polyacrylamide gel electrophoresis. Neither VP24 nor anthocyanin was detectable in dark-cultured cells, but VP24 appeared three days after the start of irradiation with light and the level of VP24 increased for up to a week. High concentrations of 2,4-D markedly inhibited the accumulation of both VP24 and anthocyanin. These results indicated that the expression of VP24, which was induced by exposure to light, was closely accompanied by the accumulation of anthocyanin in the vacuoles. VP24 was recovered as an insoluble reddish precipitate after ultracentrifugation of a lysate of anthocyanin-containing vacuoles. Immunoblot analysis indicated that this vacuolar protein was distinct from sporamin, a major storage protein of sweet potato tuberous root. These results suggest that VP24 is not an integral protein of the vacuolar membrane but tends to form aggregates via interactions with anthocyanin during extraction. VP24 may be involved in the formation of intravacuolar pigmented structures that develop in vivo in the anthocyanin-containing vacuoles of sweet potato cells in culture.
Water Analysis:  Emerging Contaminants and Current Issues (2003)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTADDITION / CORRECTIONThis article has been corrected. View the notice.Water Analysis: Emerging Contaminants and Current IssuesSusan D. RichardsonView Author Information National Exposure Research Laboratory, U.S. Environmental Protection Agency, Athens, Georgia 30605 Cite this: Anal. Chem. 2003, 75, 12, 2831–2857Publication Date (Web):May 3, 2003Publication History Published online3 May 2003Published inissue 1 June 2003https://pubs.acs.org/doi/10.1021/ac0301301https://doi.org/10.1021/ac0301301review-articleACS PublicationsCopyright © Not subject to U.S. Copyright. Published 2003 American Chemical SocietyRequest reuse permissionsArticle Views2547Altmetric-Citations85LEARN 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 SUBJECTS:Chromatography,Drinking water,Impurities,Mass spectrometry,Pest control Get e-Alerts
Identification of Distinct γ-Secretase Complexes with Different APH-1 Variants (2004)

The gamma-secretase complex catalyzes the final intramembraneous cleavage of the beta-amyloid precursor protein, liberating the neurotoxic amyloid beta-peptide implicated in Alzheimer's disease. Apart from the catalytic subunit presenilin (PS), three additional subunits, nicastrin, APH-1, and PEN-2, have been identified. In mammals, two PS homologues, PS1 and PS2, which are part of distinct gamma-secretase complexes, exist. Likewise, two APH-1 homologues, APH-1a and APH-1b, have been identified. Furthermore, two APH-1a splice forms, APH-1aS and APH-1aL, have been reported. Here we show that both APH-1a splice forms and APH-1b are expressed in peripheral and neuronal cells. APH-1aS, APH-1aL, and APH-1b form separate, proteolytically active gamma-secretase complexes containing either one of the two PSs. Deficiency of APH-1a caused a decrease in nicastrin, PS, and PEN-2 levels and an increase in the levels of APH-1b, whereas deficiency of APH-1b did not affect the levels of APH-1a or the other complex components. Consistent with this finding, we found that deficiency of APH-1a was associated with reduced gamma-secretase activity, whereas deficiency of APH-1b was not. Thus, APH-1b gamma-secretase complexes may fulfill redundant functions. Taken together, our results suggest that, dependent on the tissue expression of the individual subunits, six distinct gamma-secretase complexes composed of the known subunits can exist in human cells.
Drugs from Emasculated Hormones: The Principle of Syntopic Antagonism (Nobel Lecture) (1989)

Hormones as prototypes in the development of drugs; this was the theme of the lecture by the third recipient of the 1988 Nobel Prize in Medicine, whose research led to compounds such as propranolol 1, derived from adrenaline andused as a drug against angina pectoris illnesses, and burimamide 2, derived from histamine, used against increased gastric secretion, the cause of stomach and duodenal ulcers.
Expression of a Porphyromonas gingivalis lipid A palmitylacyltransferase in Escherichia coli yields a chimeric lipid A with altered ability to stimulate interleukin-8 secretion (2005)

In Escherichia coli the gene htrB codes for an acyltransferase that catalyses the incorporation of laurate into lipopolysaccharide (LPS) as a lipid A substituent. We describe the cloning, expression and characterization of a Porphyromonas gingivalis htrB homologue. When the htrB homologue was expressed in wild-type E. coli or a mutant strain deficient in htrB, a chimeric LPS with altered lipid A structure was produced. Compared with wild-type E. coli lipid A, the new lipid A species contained a palmitate (C16) in the position normally occupied by laurate (C12) suggesting that the cloned gene performs the same function as E. coli htrB but preferentially transfers the longer-chain palmitic acid that is known to be present in P. gingivalis LPS. LPS was purified from wild-type E. coli, the E. coli htrB mutant strain and the htrB mutant strain expressing the P. gingivalis acyltransferase. LPS from the palmitate bearing chimeric LPS as well as the htrB mutant exhibited a reduced ability to activate human embryonic kidney 293 (HEK293) cells transfected with TLR4/MD2. LPS from the htrB mutant also had a greatly reduced ability to stimulate interleukin-8 (IL-8) secretion in both endothelial cells and monocytes. In contrast, the activity of LPS from the htrB mutant bacteria expressing the P. gingivalis gene displayed wild-type activity to stimulate IL-8 production from endothelial cells but a reduced ability to stimulate IL-8 secretion from monocytes. The intermediate activation observed in monocytes for the chimeric LPS was similar to the pattern seen in HEK293 cells expressing TLR4/MD2 and CD14. Thus, the presence of a longer-chain fatty acid on E. coli lipid A altered the activity of the LPS in monocytes but not endothelial cell assays and the difference in recognition does not appear to be related to differences in Toll-like receptor utilization.
Lung glutathione and oxidative stress: implications in cigarette smoke-induced airway disease (1999)

Glutathione (GSH), a ubiquitous tripeptide thiol, is a vital intra- and extracellular protective antioxidant in the lungs. The rate-limiting enzyme in GSH synthesis is gamma-glutamylcysteine synthetase (gamma-GCS). The promoter (5'-flanking) region of the human gamma-GCS heavy and light subunits are regulated by activator protein-1 and antioxidant response elements. Both GSH and gamma-GCS expression are modulated by oxidants, phenolic antioxidants, and inflammatory and anti-inflammatory agents in lung cells. gamma-GCS is regulated at both the transcriptional and posttranscriptional levels. GSH plays a key role in maintaining oxidant-induced lung epithelial cell function and also in the control of proinflammatory processes. Alterations in alveolar and lung GSH metabolism are widely recognized as a central feature of many inflammatory lung diseases including chronic obstructive pulmonary disease (COPD). Cigarette smoking, the major factor in the pathogenesis of COPD, increases GSH in the lung epithelial lining fluid of chronic smokers, whereas in acute smoking, the levels are depleted. These changes in GSH may result from altered gene expression of gamma-GCS in the lungs. The mechanism of regulation of GSH in the epithelial lining fluid in the lungs of smokers and patients with COPD is not known. Knowledge of the mechanisms of GSH regulation in the lungs could lead to the development of novel therapies based on the pharmacological or genetic manipulation of the production of this important antioxidant in lung inflammation and injury. This review outlines 1) the regulation of cellular GSH levels and gamma-GCS expression under oxidative stress and 2) the evidence for lung oxidant stress and the potential role of GSH in the pathogenesis of COPD.
Deletion of a Single Allele of the Dkk1 Gene Leads to an Increase in Bone Formation and Bone Mass (2006)

We conclude that Dkk1 protein is a potent negative regulator of osteoblasts in vitro and in vivo. Given that a heterozygous decrease in Dkk1 expression is sufficient to induce a significant increase in bone mass, antagonizing Dkk1 should result in a potent anabolic effect.
Quantitative Kinetic Analysis of Hydrogen Transfer Reactions from Dietary Polyphenols to the DPPH Radical (2002)

Diphenylpicrylhydrazyl (DPPH) is widely used for quickly assessing the ability of polyphenols to transfer labile H atoms to radicals, a likely mechanism of antioxidant protection. This popular test generally pays no attention to the kinetics of H atom transfer, which however could be even more important than the total H-atom-donating capacities (stoichiometry, EC50) typically evaluated. In the present work, a series of dietary polyphenols belonging to the most representative families (flavonols from onion, flavanol monomers and oligomers from barley, and caffeic acid and caffeoyl esters from artichoke and endive) are characterized not only by their total stoichiometries (n(tot)) but also by their rate constants of first H atom abstraction by DPPH (k(1)), deduced from the kinetic analysis of the decay of the DPPH visible band following addition of the antioxidant. The mildly reactive DPPH radical allows a good discrimation between polyphenols, as demonstrated by the relatively large ranges of k(1) (ca. 400-5000 M(-)(1) s(-)(1)) and n(tot) (ca. 1-5) values typically measured with antioxidants having a single polyphenolic nucleus. With antioxidants displaying more than one polyphenolic nucleus (procyanidin oligomers, dicaffeoyl esters), the kinetic analysis makes it possible to demonstrate significant differences in reactivity between the subunits (two distinct k(1) values whose ratio lies in the range 3-10) and nonadditive stoichiometries.
Fluorescent PNA Probes as Hybridization Labels for Biological RNA (2006)

Fluorescent labeling of biological RNA is complicated by the narrow range of nucleoside triphosphates that can be used for biological synthesis (i.e., transcription) as well as the inability to site-specifically incorporate them into long RNA transcripts. Noncovalent strategies for labeling RNA rely on attaching fluorescent dyes to hybridization probes which deliver the dye to a specific region of the RNA through Watson-Crick base pairing. This report demonstrates the use of high-affinity peptide nucleic acid (PNA) probes in labeling mRNA transcripts with thiazole orange donor and Alexa-594 acceptor fluorophores. The PNA probes were targeted to sequences flanking splice sites in a pre-mRNA such that before splicing the PNAs were separated by >300 nucleotides (nts) whereas after splicing the separation decreased to <or=12 nts. The decreased separation led to enhanced Förster resonance energy transfer (FRET) for the spliced RNA. Bulk solution and single-molecule fluorescence experiments gave consistent results.
The Survivin saga goes in vivo (2001)

Survivin is a bifunctional protein that suppresses apoptosis and regulates cell division (1). This protein has garnered great interest as a potential drug target because its expression is among the most tumor-specific of all human gene products (2). While fetal tissues contain abundant Survivin mRNA and protein, most normal adult tissues do not. In contrast, the vast majority of tumors express Survivin protein at high levels, suggesting that reactivation of SURVIVIN gene expression occurs commonly in cancers (3).

The mechanisms by which Survivin regulates cell death and cell division are highly controversial. Indeed, even the premise that Survivin regulates apoptosis has been challenged, primarily on the grounds that Survivin homologues in yeast and Caenorhabditis elegans operate as regulators of cell division but not cell survival (reviewed in refs. 4, 5). Heretofore, the preponderance of evidence that mammalian Survivin suppresses apoptosis was based on overexpression of the protein in cultured cell lines. The absence of in vivo data on this point has now been remedied with a paper in this issue of the JCI by Altieri and colleagues (6). In an accompanying paper (7), the same investigators show how emerging knowledge about Survivin regulation might be use to develop a new gene therapy strategy for cancer.

Seeking to model events in tumors, Grossman et al. (6) placed the Survivin cDNA under the control of the keratin 14 (K14) promoter and generated transgenic mice that produce Survivin constitutively in epidermal keratinocytes. The skin is an easily accessible tissue that displays the full gamut of events relevant to tumorigenesis, including cell proliferation, differentiation, and death. Betting persons might have placed their wagers on seeing a defect in cell division or differentiation in K14-Survivin mice, but such was not the case. Instead, the keratinocytes of these Survivin-overexpressing mice demonstrated resistance to apoptosis, thus providing the first evidence that Survivin can suppress cell death in vivo. Specifically, overexpression of Survivin significantly reduced the numbers of apoptotic cells generated in the epidermis following exposure to ultraviolet-B (UVB) radiation (sunburn). While these data do not go as far as to establish a role for Survivin in homeostatic programmed cell death, they do at least indicate that the overexpression of Survivin (which is seen in many tumors) can result in an antiapoptotic state in vivo.
Virtual Displays and Virtual Environments (1997)

Our recent work on virtual environments and virtual displays is reviewed, including our efforts to establish the Virtual Environment Research, Interactive Technology, And Simulation (VERITAS) facility and our research on spatial hearing. VERITAS is a state-of -the-art multisensory facility, built around the technology. High-quality 3D audio is included and haptic interfaces are planned. The facility will support technical and non-technical users working in a wide variety of application areas. Our own research emphasizes the importance of auditory stimulation in virtual environments and complex display systems. Experiments on auditory-aided visual target acquistion, sensory conflict, sound localization in noise, and loxalization of speech stimuli are discussed.
The size of characters of compact Lie groups (1998)

Pointwise upper bounds for characters of compact, connected, simple Lie groups are obtained which enable one to prove that if μ is any central, continuous measure and n exceeds half the dimension of the Lie group, then $μ^n ∈ L^1$. When μ is a continuous,