gebhart/patrepeval huggingface dataset:
Conversion of the lac repressor into an allosterically regulated transcriptional activator for mammalian cells. (1990)

A novel mammalian regulatory system was created by using the Escherichia coli lac repressor. The lac repressor was converted into a mammalian transcriptional activator by modifying the lac repressor coding region to include a nuclear localization signal from the simian virus 40 (SV40) large tumor antigen and the transcription activation domain from the herpes simplex virus type 1 virion protein 16. The lac activator protein (LAP) fusions were potent activators of several promoters containing lac operator sequences positioned either upstream or downstream of the transcription unit. A single lac operator allowed for transactivation, whereas multiple operators acted synergistically when separated by a small distance. Promoters containing 14 or 21 operator sequences were induced at least 1,000-fold in response to LAP, reaching levels of activity 20 to 30 times greater than that of the SV40 early promoter in HeLa cells. Activation was strongly inhibited by isopropyl-beta-D-thiogalactoside (IPTG), indicating that LAP retained the functions needed for allosteric regulation. LAP was bifunctional, also acting as a repressor of expression of an SV40 promoter containing an operator immediately downstream of the TATA box. Finally, genetic selection schemes were developed such that LAP-expressing cell lines can be generated at high frequency from either established or primary cells in culture.
A Pilot Study of MUC-1/CEA/TRICOM Poxviral-Based Vaccine in Patients with Metastatic Breast and Ovarian Cancer (2011)

Some patients who had limited tumor burden with minimal prior chemotherapy seemed to benefit from the vaccine. Further studies to confirm these results are warranted.
Development and application of siRNA expression vector (2002)

RNA interference (RNAi) is a sequence-specific silencing phenomenon, which is induced by double-stranded RNA (dsRNA) and mediated through an evolutionarily conserved mechanism from plants to mammals. In mammalian cells, it has recently been reported that 21- or 22-nucleotide (nt) RNAs with 2-nt 3' overhangs (siRNA) induce RNAi without induction of the dsRNA-dependent inhibition of protein synthesis, known as the host defense system against viral infections. Moreover, we and other have developed siRNA expression systems utilizing a pol III promoter. Here we report a comparative analysis among various siRNA expression vectors and also demonstrate a regulatable RNAi in cells by using a tetracycline-controlled U6 promoter.
Gene therapy for coronary disease. (2000)

Gene transfer offers an approach to the study and treatment of coronary disease. The localized nature of vascular diseases like restenosis has made the application of genetic material an attractive therapeutic option. Viral and non viral vectors have been developed to facilitate the entry of foreign DNA into cells. Vector improvement and production, demonstration of vector safety and therapeutic efficacy are among the main present challenges. Therapeutic angiogenesis using gene transfer is a new strategy for the treatment of coronary disease. This approach is currently being investigated in clinical trials in patients with coronary diseases. Other potential targets for genetic treatment in cardiovascular diseases include thrombosis, reendothelialization, and extracellular matrix synthesis.
Experimental intraabdominal candidiasis in rabbits: therapy with low-total-dose intravenous amphotericin B (1981)

By using a recently developed rabbit model, we examined the efficacy of relatively low-total-dose intravenous amphotericin B (Am-B; 7 to 14 mg/kg) in the treatment of intraabdominal candidiasis due to Candida albicans. Forty-eight percent of the rabbits developed evidence of hematogenously disseminated infection (Candida endophthalmitis) before therapy. By day 7 of therapy, there was a significant decrease in the mean log10 colony-forming units per gram of peritoneal abscess in comparison with both pretherapy cultures and concomitantly sacrificed controls (no Am-B treatment; P less than 0.25). By day 11 of therapy, peritoneal abscesses were sterilized by Am-B, whereas control rabbit cultures remained positive. In contrast, low-dose Am-B therapy produced no significant decrease in colony-forming units per gram of renal or chorioretinal abscess in rabbits which developed hematogenously disseminated candidiasis. Serum Am-B levels approached or exceeded the minimal fungistatic concentrations for this C. albicans strain in most animals tested. Low-dose Am-B was effective in eradicating intraabdominal candidiasis, but was not curative when extraperitoneal dissemination occurred.
Salmonella typhimurium attachment to human intestinal epithelial monolayers: transcellular signalling to subepithelial neutrophils. (1993)

In human intestinal disease induced by Salmonella typhimurium, transepithelial migration of neutrophils (PMN) rapidly follows attachment of the bacteria to the epithelial apical membrane. In this report, we model those interactions in vitro, using polarized monolayers of the human intestinal epithelial cell, T84, isolated human PMN, and S. typhimurium. We show that Salmonella attachment to T84 cell apical membranes did not alter monolayer integrity as assessed by transepithelial resistance and measurements of ion transport. However, when human neutrophils were subsequently placed on the basolateral surface of monolayers apically colonized by Salmonella, physiologically directed transepithelial PMN migration ensued. In contrast, attachment of a non-pathogenic Escherichia coli strain to the apical membrane of epithelial cells at comparable densities failed to stimulate a directed PMN transepithelial migration. Use of the n-formyl-peptide receptor antagonist N-t-BOC-1-methionyl-1-leucyl-1- phenylalanine (tBOC-MLP) indicated that the Salmonella-induced PMN transepithelial migration response was not attributable to the classical pathway by which bacteria induce directed migration of PMN. Moreover, the PMN transmigration response required Salmonella adhesion to the epithelial apical membrane and subsequent reciprocal protein synthesis in both bacteria and epithelial cells. Among the events stimulated by this interaction was the epithelial synthesis and polarized release of the potent PMN chemotactic peptide interleukin-8 (IL-8). However, IL-8 neutralization, transfer, and induction experiments indicated that this cytokine was not responsible for the elicited PMN transmigration. These data indicate that a novel transcellular pathway exists in which subepithelial PMN respond to lumenal pathogens across a functionally intact epithelium. Based on the known unique characteristics of the intestinal mucosa, we speculate that IL-8 may act in concert with an as yet unidentified transcellular chemotactic factor(s) (TCF) which directs PMN migration across the intestinal epithelium.
Endotoxin-induced uveitis in the rat. The significance of intraocular interleukin-6. (1992)

The potential role of interleukin-6 (IL-6) was studied as an inflammatory mediator of endotoxin (or lipopolysaccharide [LPS])-induced uveitis (EIU) in the rat. In young Lewis rats, levels of intraocular IL-6, but not serum IL-6, correlated with the severity of uveitis and with aqueous humor protein levels in response to foot pad injections of LPS (P less than 0.001). Adult Lewis rats did not develop uveitis and had no intraocular IL-6, although IL-6 was released systemically. Resistance to EIU and absence of IL-6 levels in the aqueous humor, despite the ability to release serum IL-6, also were observed in brown Norway rats, irrespective of age and weight. Intravitreal injection of as little as 1 ng of human recombinant IL-6 induced uveitis in young Lewis rats. In adult Lewis rats, and in young animals made tolerant to LPS, intravitreal IL-6 still caused substantial leakage of plasma proteins into the anterior chamber but no influx of inflammatory cells. As early as 2 hr after intravitreal injection of IL-6, immunohistochemical analysis showed invasion of the iris, corneal stroma, and anterior chamber by polymorphonuclear leukocytes (PMN) and expression of major histocompatibility complex (MHC) class II antigen in the retina by large cells that were macrophage-marker ED2 negative. This was followed by massive PMN infiltration of the retinal layers and vitreous. The MHC class II antigen expression of ciliary and iris epithelium occurred at a later stage (greater than 8 hr).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of Planting Density on Growth and Yield in Cassia obtusifolia. L. (1997)

This study was conducted to investigate how a labor saving for conventional hand sowing and respond to major agronomic traits under different planting density in 1993 and 1994. Each trial was a randomized block split plot with row spacing as the main plots and hill spacing as subplots. Sowing rate appeared lower in 20 or 25cm hill spacing using machine seeder than in hand sowing. Sowing time required reduced more 121 hours per hectare in 60cm row, 20cm hill spacings using machine seeder than in hand sowing. Increasing row and hill spacings reduced number of seedling stand per unit . Both number of pods per plant and grain weight per plant and showed highly increase in wide planting. Best yield obtained in 60cm row, 20cm hill spacing using machine seeder. Accumulative mean air temperature was positively correlated with stem height, number of pods per plant and yield, otherwise accumulative rainfall was negatively correlated with ones. A highly significant negative correlation was showed between number of seedling stand per unit and number of branches, number of pods per plant, grain weight per plant and yield. Yield was positively correlated with number of branches, number of pods per plant and grain weight per plant.
Development of a Series of Near-Infrared Dark Quenchers Based on Si-rhodamines and Their Application to Fluorescent Probes (2015)

Near-infrared (NIR) fluorescent probes based on the Förster resonance energy transfer (FRET) mechanism have various practical advantages, and their molecular design is generally based on the use of NIR dark quenchers, which are nonfluorescent dyes, as cleavable FRET acceptors. However, few NIR dark quenchers can quench fluorescence in the Cy7 region (over 780 nm). Here, we describe Si-rhodamine-based NIR dark quenchers (SiNQs), which show broad absorption covering this region. They are nonfluorescent independently of solvent polarity and pH, probably due to free rotation of the bond between the N atom and the xanthene moiety. SiNQs can easily be structurally modified to tune their water-solubility and absorption spectra, enabling flexible design of appropriate FRET pair for various NIR fluorescent dyes. To demonstrate the usefulness of SiNQs, we designed and synthesized a NIR fluorescent probe for matrix metalloproteinase (MMP) activity using SiNQ780. This probe 1 could detect MMP activity in vitro, in cultured cells and in a tumor-bearing mouse, in which the tumor was clearly visualized, by NIR fluorescence. We believe SiNQs will be useful for the development of a wide range of practical NIR fluorescent probes.
A Phase 1 Study to Evaluate the Pharmacokinetics and Safety of Cabotegravir in Patients With Hepatic Impairment and Healthy Matched Controls (2019)

Cabotegravir is an investigational integrase inhibitor in development for the treatment and pre-exposure prophylaxis of HIV-1 infection. Liver disease is a major cause of morbidity and mortality in HIV-infected individuals and can impact the pharmacokinetics (PK) of HIV medications. This phase 1 study evaluated the PK of cabotegravir in individuals with moderate hepatic impairment (n = 8) versus healthy controls (n = 8). Participants received a single oral cabotegravir 30-mg tablet and underwent PK sampling to determine total and unbound plasma cabotegravir concentrations. Calculated geometric least-squares mean ratios (90% confidence intervals) for individuals with hepatic impairment versus healthy controls were 0.73 (0.50-1.06) for AUC<sub>0-∞</sub> , 0.69 (0.51-0.93) for C<sub>max</sub> , 1.40 (0.80-2.46) for unbound concentration (CU) 2 hours postdose, 1.55 (0.82-2.94) for CU at 24 hours, 2.14 (1.57-2.90) for unbound fraction (FU) at 2 hours, and 1.90 (1.14-3.18) for FU at 24 hours. Adverse events (AEs) occurred in 2 individuals with hepatic impairment and 3 healthy controls and were grade 1/2 in severity. No participant discontinued because of AEs. Increased FU resulted in a modest decrease in total plasma exposure not considered clinically relevant. We conclude that cabotegravir may be administered without dose adjustment in patients with mild to moderate hepatic impairment.
Omega-3 and omega-6 fatty acids have distinct effects on endothelial fatty acid content and nitric oxide bioavailability (2021)

Treatment with high dose icosapent ethyl (IPE), an ethyl ester of the omega-3 fatty acid eicosapentaenoic acid (EPA), significantly reduced ischemic events in patients with either cardiovascular disease (CV) or diabetes plus other risk factors (REDUCE-IT) but the mechanism is not well understood. We compared the effects of EPA, docosahexaenoic acid (DHA), and the omega-6 fatty acid arachidonic acid (AA) on bioavailability of nitric oxide (NO) and fatty acid composition. Human umbilical vein endothelial cells (HUVECs) were pretreated with EPA, DHA, or AA (10 µM). Cells were stimulated with calcium ionophore and NO and peroxynitrite (ONOO<sup>-</sup>) were measured using porphyrinic nanosensors. Levels of EPA, DHA, AA and other fatty acids were measured by gas chromatography (GC). EPA treatment caused the greatest NO release (18%, p < 0.001) and reduction in ONOO<sup>-</sup> (13%, p < 0.05) compared to control; the [NO]/[ ONOO<sup>-</sup>] ratio increased by 35% (p < 0.001). DHA treatment increased NO levels by 12% (p < 0.01) but had no effect on ONOO<sup>-</sup> release. AA did not affect either NO or ONOO<sup>-</sup> release. Fatty acid treatments increased their respective levels in endothelial cells. EPA levels increased 10-fold to 4.59 mg/g protein (p < 0.001) with EPA treatment and the EPA/AA ratio increased by 10-fold (p < 0.001) compared to vehicle. Only EPA increased docosapentaenoic acid (DPA, omega-3) levels by 2-fold (p < 0.001). AA alone decreased the EPA/AA ratio 4-fold (p<0.001). These findings support a preferential benefit of EPA on endothelial function and omega-3 fatty acid content.
Clusterin: Physiologic and pathophysiologic considerations (1995)

Clusterin is a heterodimeric glycoprotein produced by a wide array of tissues and found in most biologic fluids. A number of physiologic functions have been proposed for clusterin based on its distribution and in vitro properties. These include complement regulation, lipid transport, sperm maturation, initiation of apoptosis, endocrine secretion, membrane protection, and promotion of cell interactions. A prominent and defining feature of clusterin is its induction in such disease states as glomerulonephritis, polycystic kidney disease, renal tubular injury, neurodegenerative conditions including Alzheimer's disease, atherosclerosis, and myocardial infarction. The expression of clusterin in these states is puzzling, from the specific molecular species and cellular pathways eliciting such expression, to the roles subserved by clusterin once induced. This review will discuss these physiologic and pathophysiologic aspects of clusterin and speculate on its role in disease.
The signal sequence interacts with the methionine-rich domain of the 54-kD protein of signal recognition particle. (1991)

The signal sequence of nascent preprolactin interacts with the 54-kD protein of the signal recognition particle (SRP54). To identify the domain or site on SRP54 that interacts with the signal sequence we used a photocross-linking approach followed by limited proteolysis and immunoprecipitation using anti-peptide antibodies specific for defined regions of SRP54. We found that the previously identified methionine-rich RNA-binding domain of SRP54 (SRP54M domain) also interacts with the signal sequence. The smallest fragment that was found to be crosslinked to the signal sequence comprised the COOH-terminal 6-kD segment of the SRP54M domain. No cross-link to the putative GTP-binding domain of SRP54 (SRP54G domain) was found. Proteolytic cleavage between the SRP54M domain and SRP54G domain did not impair the subsequent interaction between the signal sequence and the SRP54M domain. Our results show that both the RNA binding and signal sequence binding functions of SRP54 are performed by the SRP54M domain.
A partial genomic DNA clone for the alpha subunit of the mouse complement receptor type 3 and cellular adhesion molecule Mac-1. (1986)

A genomic clone coding for the alpha subunit of the mouse complement receptor type 3 and the cellular adhesion molecule Mac-1 has been isolated directly from a genomic library using synthetic oligonucleotide probes based on the amino-terminal amino acid sequence of the protein. The identity of the clone has been established by DNA sequencing and in vitro translation of hybrid-selected mRNA. The gene is present in a single copy in the murine genome. The region containing the amino-terminal exon has been sequenced. RNA gel blotting shows that the Mac-1 alpha-subunit mRNA is 6 kilobases in length. Mac-1 alpha-subunit mRNA is present in macrophages but not T lymphoma or L cells. During gamma interferon-stimulated maturation of the mouse premyelocytic cell line M1, Mac-1 alpha-subunit mRNA is induced. This corresponds with the tissue distribution of the Mac-1 alpha subunit, showing expression is regulated at least partially at the message level.
Monoclonal antibody-related drugs for cancer therapy (2013)

Much progress has been made during the last few decades in the treatment of malignancies. Many types of cancer cells comprising the tumor mass carry molecular markers that are not expressed or are expressed at much lower levels in normal cells. These findings provide new leads to drug design and development of therapeutic strategies involving monoclonal antibodies (mAbs) or related antibody drugs to treat malignancies. This article reviews recent advances in this targeting approach with a focus on the evolution and current use of prospective antibody drugs as effective ways to treat cancer. Additionally, the development of prospective antibody-drug conjugates will also be briefly described.
Charge Reduction Electrospray Mass Spectrometry (1999)

A new mass spectrometric technique, charge reduction electrospray mass spectrometry (CREMS), allowing the analysis of complex mixtures of biological molecules is described. The charge state of ions produced by electrospray ionization may be reduced in a controlled manner to yield predominantly singly charged ions through reactions with bipolar (i.e., both positively and negatively charged) ions generated using a 210Po alpha particle source. The electrospray-generated multiply charged ions undergo charge reduction in a "neutralization chamber" positioned before the entrance nozzle to the mass spectrometer. The ions are detected using a commercial orthogonal electrospray time-of-flight mass spectrometer, although the neutralization chamber can be adapted to virtually any mass analyzer. The CREMS results obtained exhibit a signal intensity drop-off with increasing oligonucleotide size similar to that observed with matrix-assisted laser desorption/ionization mass spectrometry. Proton-transfer reactions were found to be responsible for reducing charge on proteins and oligonucleotides in both positive and negative ion mode.
<title>Targeted Type 1 phototherapeutic agents using azido-peptide bioconjugates</title> (2001)

Five peptides binding to somatostatin and bombesin receptors were conjugated to 4-azido-2,3,4,6-tetrafluorophenylbenzoic acid, a Type 1 photosensitizer, at the N-terminal position. The receptor affinities were determined by competition binding assay using two different pancreatic tumor cell lines, CA20948 and AR42-J, that expresses somatostatin-2 (SST-2) and bombesin receptors receptively. All compounds exhibited high receptor specificity, i.e., the IC<SUB>50</SUB> values ranged between 1.0 to 64.0 nM. These conjugates may be useful for targeted Type 1 phototherapy via the generation of nitrenes at the cell surfaces expressing these receptors.
Detection of hepatitis C virus RNA by a combined reverse transcription-polymerase chain reaction assay (1993)

Amplification of RNA by the polymerase chain reaction (PCR) is normally a two-step process requiring separate enzymes and buffer conditions. We describe a combined reverse transcription-PCR (RT-PCR) assay for hepatitis C virus (HCV) RNA amplification in which a single enzyme and buffer condition are used. In this assay, both the RT and PCR steps are carried out with the thermoactive DNA polymerase of Thermus thermophilus. A transcription vector containing HCV sequences has also been constructed to generate quantifiable HCV RNA templates that can be used to optimize reaction conditions and to assess the efficiency of amplification. Amplification from &lt; or = 100 copies of RNA was detected reproducibly by gel electrophoresis. The assay sensitivity was increased to 10 RNA copies by hybridization to a probe. The patterns of viremia in three individuals infected with HCV were examined by amplification of HCV RNA from plasma samples collected serially over a period of 1 year. These results were correlated with the times of seroconversion and the onset of rise in levels of alanine aminotransferase in serum. In all three subjects, HCV RNA was detected prior to seroconversion and the initial rise in levels of alanine aminotransferase in serum. Upon seroconversion, HCV RNA fell to a level below the detection limit of the assay. This pattern of transient viremia appears to be characteristic of acute, resolving HCV infections. The combined RT-PCR assay is a sensitive method which circumvents the problems associated with PCR amplification of RNA. Using this assay, we demonstrated that three donors infected by the same index case all have similar patterns of viremia.
Interlacing molecular threads on transition metals: catenands, catenates, and knots (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInterlacing molecular threads on transition metals: catenands, catenates, and knotsJean Pierre SauvageCite this: Acc. Chem. Res. 1990, 23, 10, 319–327Publication Date (Print):October 1, 1990Publication History Published online1 May 2002Published inissue 1 October 1990https://pubs.acs.org/doi/10.1021/ar00178a001https://doi.org/10.1021/ar00178a001research-articleACS PublicationsRequest reuse permissionsArticle Views1784Altmetric-Citations438LEARN 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