gebhart/patrepeval huggingface dataset:
Mechanisms controlling differential promoter-occupancy by the yeast forkhead proteins Fkh1p and Fkh2p: implications for regulating the cell cycle and differentiation (2001)

The roles of DNA and Mcm1p interactions in determining the overlapping and distinct functions of the yeast cell cycle regulatory transcription factors Fkh1p and Fkh2p were examined. Full-length recombinant Fkh1p and Fkh2p were purified and their binding to bona fide promoters examined in vitro. Each protein bound a variety of target promoters with similar specificity in vitro, consistent with the observation that these proteins bind common promoters in vivo. However, in vivo, the Fkh1p and Fkh2p occupied different target promoters to different extents, suggesting that each was primarily responsible for controlling a different set of genes. Additional in vitro studies provided a mechanistic explanation for this differential promoter-occupancy. Specifically, the Fkh2p, but not the Fkh1p, was capable of binding cooperatively with Mcm1p. The Mcm1p-Fkh2p cooperative binding was enhanced by, but did not require, the presence of a Mcm1p-binding site within a target promoter. Consistent with these data, Mcm1p was present at Fkh-controlled promoters in vivo regardless of whether they contained Mcm1p-binding sites, suggesting a role for Mcm1p at promoters not thought previously to be under Mcm1p control. Analysis of Fkh1p and Fkh2p binding to promoter targets in vivo by use of mutant strains indicated that the two proteins compete for promoter-occupancy at a number of target promoters. We postulate that Fkh1p and a stable Fkh2p/Mcm1p complex compete for binding to target promoters and that the levels and/or binding activity of Fkh1p, but not Fkh2p, are most limiting for promoter-occupancy in vivo. Interestingly, the in vitro DNA-binding assays, using a variety of promoter targets, revealed that bona fide Fkh target promoters contained two or more Fkh-binding sites that allowed the Fkh1p and Fkh2p proteins to form multiple protein-DNA complexes in vitro. Multiple Fkh-binding sites may be a distinguishing feature of bona fide Fkh promoters in yeast and other organisms.
Design of imidazole-containing endosomolytic biopolymers for gene delivery (2000)

The development of safe and effective gene delivery agents poses a great challenge in the quest to make human gene therapy a reality. Cationic polymers represent one important class of materials for gene delivery, but to date they have shown only moderate efficiency. Improving the efficiency will require the design of new polymers incorporating optimized gene delivery properties. For example, inefficient release of the DNA/polymer complex from endocytic vesicles into the cytoplasm is one of the primary causes of poor gene delivery. Here we report the synthesis of a biocompatible, imidazole-containing polymer designed to overcome this obstacle. DNA/polymer polyplexes incorporating this polymer were shown to have desirable physico-chemical properties for gene delivery and are essentially nontoxic. Using this system, mammalian cells in vitro were transfected in the absence of any exogenous endosomolytic agent such as chloroquine.
Determination by systematic deletion of the amino acids essential for catalysis by ricin A chain. (1992)

The A chain of ricin is a RNA N-glycosidase that inactivates ribosomes by depurination of a single adenosine in 28S rRNA. Of the 267 amino acids in the protein, 222 (83%) could be deleted from one or another of 74 mutants without loss of the capacity of the protein to recognize a single nucleotide from among the 7000 in ribosomes or to catalyze hydrolysis.
Eliminating Carcinogenic Acetaldehyde By Cysteine From Saliva During Smoking (2006)

Tobacco smoking is one of the strongest risk factors not only for lung cancer but also for cancers of the upper gastrointestinal tract. Acetaldehyde has been shown to dissolve into the saliva during smoking and to be a local carcinogen in the human upper digestive tract. Cysteine can bind to acetaldehyde and eliminate its toxicity. We developed a tablet that releases cysteine into the oral cavity during smoking and could therefore be a potential chemopreventive agent against toxicity of tobacco smoke. In this study, the efficacy of l-cysteine-containing tablets to reduce the carcinogenic acetaldehyde in the saliva during tobacco smoking was examined. Seven volunteers smoked five cigarettes. During every smoking period, each volunteer sucked a blinded tablet containing 0, 1.25, 2.5, 5, or 10 mg of l-cysteine. Acetaldehyde was analyzed from salivary samples gas chromatographically at 0, 5, and 10 minutes from the beginning of the smoking. All tablets containing l-cysteine reduced highly significantly the salivary acetaldehyde; 5 mg of l-cysteine was the minimum concentration to totally eliminate the acetaldehyde from saliva. The mean salivary acetaldehyde concentrations in samples collected immediately after smoking with 0, 1.25, 2.5, 5, or 10 mg of l-cysteine were 228+/-115 micromol/L, 85+/-42 micromol/L (P=0.007), 9+/-7 micromol/L, 0.09+/- 0.2 micromol/L, 0+/- 0 micromol/L (P<0.001), respectively. In conclusion, carcinogenic acetaldehyde could be totally inactivated in the saliva during smoking by sucking tablet containing 5 mg of l-cysteine. Even a small reduction of the carcinogenicity of cigarette smoke could gain benefit at the population level. Hence, this finding warrants for further clinical trials for l-cysteine tablet in the prevention of upper digestive tract cancers in smokers.
Motility, proliferation, and egress to the circulation of human AML cells are elastase dependent in NOD/SCID chimeric mice (2005)

The role of the proteolytic enzyme elastase in motility and proliferation of leukemic human acute myeloblastic leukemia (AML) cells is currently unknown. We report a correlation between abnormally high levels of elastase in the blood of AML patients and the number of leukemic blast cells in the circulation. In AML cells, we observed expression of cell-surface elastase, which was regulated by the chemokine stromal cell-derived factor-1 (SDF-1). In vitro inhibition of elastase prevented SDF-1-induced cell polarization, podia formation, and reduced migration of human AML cells as well as their adhesion. Elastase inhibition also significantly impaired in vivo homing of most human AML cells to the bone marrow (BM) of nonobese diabetic-severe combined immunodeficient (NOD/SCID)/beta-2 microglobulin knock-out (B2m null) mice that underwent transplantation. Moreover, in vitro proliferation of AML cells was elastase dependent. In contrast, treatment with elastase inhibitor enhanced the proliferation rate of human cord blood CD34+ cells, including primitive CD34+/CD38- cells, and their in vivo homing. Finally, NOD/SCID mice previously engrafted with human AML cells and treated with elastase inhibitor had significantly reduced egress of leukemic cells into the circulation. Taken together, our data demonstrate that human AML cells constitutively secrete and express SDF-1-dependent cell-surface elastase, which regulates their migration and proliferation.
History-based access control for mobile code (1998)

Article History-based access control for mobile code Share on Authors: Guy Edjlali Dept. of ECE Wayne State University Detroit Dept. of ECE Wayne State University DetroitView Profile , Anurag Acharya Dept. of Computer Science, University of California, Santa Barbara, CA Dept. of Computer Science, University of California, Santa Barbara, CAView Profile , Vipin Chaudhary Dept. of ECE Wayne State University Detroit Dept. of ECE Wayne State University DetroitView Profile Authors Info & Claims CCS '98: Proceedings of the 5th ACM conference on Computer and communications securityNovember 1998 Pages 38–48https://doi.org/10.1145/288090.288102Online:01 November 1998Publication History 88citation993DownloadsMetricsTotal Citations88Total Downloads993Last 12 Months16Last 6 weeks1 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
The effects of combined treatment with beta1-selective receptor antagonists and lipid-lowering drugs on fat metabolism and measures of fatigue during moderate intensity exercise: a placebo-controlled study in healthy subjects (1997)

Aims We examined the effects of different combinations of b 1 -selective adrenoceptor blockers and lipid-lowering drugs, on fat metabolism and fatigue during moderate intensity exercise in 14 healthy young volunteers.Methods The study was a randomized crossover design, each subject completing 5, 90 min walks at 50% of predetermined maximal oxygen uptake (VO 2 max), one following each 3 day treatment period with either: atenolol 100 mg and bezafibrate 400 mg, atenolol 100 mg and fluvastatin 40 mg, metoprolol CR 100 mg and bezafibrate 400 mg, metoprolol CR 100 mg and fluvastatin 40 mg, or placebo.Results Plasma free fatty acid (FFA) concentration during exercise was significantly reduced on all treatments, in comparison with placebo, P=0.0001.Following 90 min of exercise FFA levels were as follows: placebo 573 mmol l -1 (105-1041), metoprolol CR+fluvastatin 277 mmol l -1 (0-647), metoprolol CR+bezafibrate 182 mmol l -1 (0-396), atenolol+fluvastatin 211 mmol l -1 (0-511), and atenolol+bezafibrate 123 mmol l -1 (0-352).Total fat oxidation during exercise was also reduced on all treatments in comparison with placebo: 38.1% (2-74), compared with 29.1% (0-61) on metoprolol CR+fluvastatin, P=0.02, 26.2% (2-51) on metoprolol CR+bezafibrate, P=0.002, 25.5% (3-48) on atenolol+fluvastatin, P= 0.009, and 22.8% (0-47) on atenolol+bezafibrate treatment, P=0.0002.Plasma ammonia concentration was elevated on all treatments during exercise in comparison with placebo.After 90 min of exercise, plasma ammonia levels were as follows: placebo 37 mmol l -1 (0-84), metoprolol CR+fluvastatin 56 mmol l -1 (2-110), metoprolol CR+bezafibrate 79 mmol l -1 (0-167), atenolol+fluvastatin 90 mmol l -1 (10-170), and atenolol+bezafibrate 100 mmol l -1 26-174).In comparison with placebo, metoprolol CR+fluvastatin had the least adverse impact on measures of perceived exertion and the 'feeling scale' during exercise.Metoprolol CR+bezafibrate, atenolol+fluvastatin, and atenolol+bezafibrate treatments had greater adverse effects, particularly on perceived 'cardiorespiratory effort' and 'feeling scale' scores.Conclusions In healthy volunteers, combinations of b 1 -selective blockers and lipidlowering drugs were associated with significant reductions in fat metabolism, increased plasma ammonia levels, and raised the perception of effort during exercise, in comparison with placebo.Metoprolol CR+fluvastatin had the least effect, combinations metoprolol CR+bezafibrate and atenolol+fluvastatin had intermediate effects, and atenolol+bezafibrate had the most adverse effect.
Targeted next generation sequencing identified a high frequency genetic mutated profile in wood smoke exposure-related lung adenocarcinoma patients (2018)

Lung adenocarcinoma patients with WSE showed a distinctive mutated profile for the SMARCB1, ATM, EGFR exon 7, RET and KDR genes. ECOG status and KDR gene mutations were significantly associated with poor prognosis.
Cloning and sequence analysis of cDNA for rat liver uricase. (1988)

We have isolated cDNA clones for rat liver uricase using an oligonucleotide corresponding to the N-terminal sequence of 8 amino acids. The nucleotide sequences of the cDNAs have been determined, and the amino acid sequence of the protein deduced. A 867-base open reading frame coding for 289 amino acids, corresponding to a molecular mass of 33,274 daltons, was confirmed by matching eight sequences of a total of 53 amino acids from peptide sequence analyses of the fragments generated by lysyl endopeptidase digestion of purified rat liver uricase. The deduced amino acid sequence of rat liver uricase shares 40% homology with that of soybean nodulin-specific uricase and has an N-terminal extension of 7 amino acids. In contrast, soybean uricase has a C-terminal extension of 12 amino acids, which is presumably the result of local gene duplication. Completely different N- and C-terminal structures of the two uricases suggest that the signals for targeting the proteins to the peroxisome are not located on the terminal continuous stretches of amino acids.
The effect of base-emitter spacers and strain dependent densities of states in Si/Si/sub 1-x/Ge/sub x//Si heterojunction bipolar transistors (2003)

The authors describe two effects which can significantly affect the transport of electrons across the base region of Si-Si/sub 1-x/Ge/sub x/-Si heterojunction bipolar transistors and limit the effective bandgap reduction. These effects are the formation of a parasitic electron barrier due to a nonabrupt base-emitter junction and the reduction of the density of states in the Si/sub 1-x/Ge/sub x/ base layer because of the anisotropic strain. Junction spacers have been found to eliminate the parasitic barriers for optimum devices. For optimum device performance it is necessary to keep the Si-Si/sub 1-x/Ge/sub x/ interfaces in the junction depletion region. The strain dependence of the densities of states in the base region lowers collector current.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
User Authentication: A State-of-the-Art Review (1991)

Access control of computing systems is considered a key issue among Information Systems managers. There are different methods available to computing systems to ensure a proper authentication of a user. Authentication mechanisms can use simple user-generated passwords to complicated combinations of passwords and physical characteristics of the user (i.e., voice recognition device, retina scanner, signature recognition device, etc.). This thesis looks at the various authentication mechanisms available to a security manager. It describes how different authentication mechanisms operate and the advantages and disadvantages associated with each mechanism. It also reports on several commercially available software products that support the user authentication process. Finally, a discussion of password use in the military environment and the unique requirements of the Department of Defense.
Structural basis for specific binding of Polycomb chromodomain to histone H3 methylated at Lys 27 (2003)

The chromodomain of Drosophila Polycomb protein is essential for maintaining the silencing state of homeotic genes during development. Recent studies suggest that Polycomb mediates the assembly of repressive higher-order chromatin structures in conjunction with the methylation of Lys 27 of histone H3 by a Polycomb group repressor complex. A similar mechanism in heterochromatin assembly is mediated by HP1, a chromodomain protein that binds to histone H3 methylated at Lys 9. To understand the molecular mechanism of the methyl-Lys 27 histone code recognition, we have determined a 1.4-Å-resolution structure of the chromodomain of Polycomb in complex with a histone H3 peptide trimethylated at Lys 27. The structure reveals a conserved mode of methyl-lysine binding and identifies Polycomb-specific interactions with histone H3. The structure also reveals a dPC dimer in the crystal lattice that is mediated by residues specifically conserved in the Polycomb family of chromodomains. The dimerization of dPC can effectively account for the histone-binding specificity and provides new mechanistic insights into the function of Polycomb. We propose that self-association is functionally important for Polycomb.
Experience with the virtual notebook system (1994)

The Virtual Notebook System (VNS) is a distributed collaborative hypertext system that has made a successful transition from research prototype to commercial product. Experience in developing and deploying the VNS in diverse settings including biomedical research, undergraduate education, and collaborative system prototyping has developed insight into the use of systems for computer-supported cooperative work (CSCW). This paper provides a brief overview of the VNS, discusses some of its strengths and weaknesses with respect to collaboration, and draws some conclusions about the impact of metaphor and extensibility on the collaborative process.
3D reconstruction of coronary arteries using Frequency Domain Optical Coherence Tomography images and biplane angiography (2012)

The aim of this study is to describe a new method for three-dimensional (3D) reconstruction of coronary arteries using Frequency Domain Optical Coherence Tomography (FD-OCT) images. The rationale is to fuse the information about the curvature of the artery, derived from biplane angiographies, with the information regarding the lumen wall, which is produced from the FD-OCT examination. The method is based on a three step approach. In the first step the lumen borders in FD-OCT images are detected. In the second step a 3D curve is produced using the center line of the vessel from the two biplane projections. Finally in the third step the detected lumen borders are placed perpendicularly onto the path based on the centroid of each lumen border. The result is a 3D reconstructed artery produced by all the lumen borders of the FD-OCT pullback representing the 3D arterial geometry of the vessel.
Lipoxin A4 Analogs Attenuate Induction of Intestinal Epithelial Proinflammatory Gene Expression and Reduce the Severity of Dextran Sodium Sulfate-Induced Colitis (2002)

The anti-inflammatory eicosanoid lipoxin A(4) (LXA(4)), aspirin-triggered 15-epi-LXA(4), and their stable analogs down-regulate IL-8 secretion and subsequent recruitment of neutrophils by intestinal epithelia. In an effort to elucidate the mechanism by which these lipid mediators modulate cellular proinflammatory programs, we surveyed global epithelial gene expression using cDNA microarrays. LXA(4) analog alone did not significantly affect expression of any of the >7000 genes analyzed. However, LXA(4) analog pretreatment attenuated induction of approximately 50% of the 125 genes up-regulated in response to the gastroenteritis-causing pathogen Salmonella typhimurium. A major subset of genes whose induction was reduced by LXA(4) analog pretreatment is regulated by NF-kappaB, suggesting that LXA(4) analog was influencing the activity of this transcription factor. Nanomolar concentrations of LXA(4) analog reduced NF-kappaB-mediated transcriptional activation in a LXA(4) receptor-dependent manner and inhibited induced degradation of IkappaBalpha. LXA(4) analog did not affect earlier stimulus-induced signaling events that lead to IkappaBalpha degradation, such as S. typhimurium-induced epithelial Ca(2+) mobilization or TNF-alpha-induced phosphorylation of IkappaBalpha. To establish the in vivo relevance of these findings, we examined whether LXA(4) analogs could affect intestinal inflammation in vivo using the mouse model of DSS-induced inflammatory colitis. Oral administration of LXA(4) analog (15-epi-16-para-fluoro-phenoxy-LXA(4), 10 microg/day) significantly reduced the weight loss, hematochezia, and mortality that characterize DSS colitis. Thus, LXA(4) analog-mediated down-regulation of proinflammatory gene expression via inhibition of the NF-kappaB pathway can be therapeutic for diseases characterized by mucosal inflammation.
Molecular recognition between oligopeptides and nucleic acids: DNA binding selectivity of a series of 1,2,4-triazole-containing lexitropsins (1991)

The synthesis of a series of 1,2,4-triazole-containing oligopeptide lexitropsins related to the natural antitumor antibiotic distamycin is described. The binding properties of these new agents to both native DNAs and synthetic polydeoxyribonucleotides were determined by UV absorption and circular dichroism studies. The DNA binding and sequence selectivity of these agents have been determined by complementary strand MPE footprinting on two restriction fragments of pBR322 DNA. The lexitropsins bearing one 1,2,4-triazole moiety bind to AT sequences like distamycin but also tolerate GC sites. However, 3, which contains two contiguous 1,2,4-triazole moieties, appears not to recognize AT stretches and demands two consecutive GC bases in the middle of a four-base recognition site. The triazole lexitropsins avoid ATTT (4264-4267) and AAAA (4273-4276) to which distamycin binds strongly to the EcoRI/Hind III fragment. Determination of pKa values indicates the 1,2,4-triazole units are protonated under physiological conditions. The avoidance of AT stretches and the recognition of GC base sites by 3 suggest molecular recognition in these cases is determined, not by electrostatic effects, but rather by invoking a hydrogen bond between the triazole 4-nitrogen and G-2NH2 in the minor groove.
Dissection of the Autophagosome Maturation Process by a Novel Reporter Protein, Tandem Fluorescent-Tagged LC3 (2007)

During the process of autophagy, autophagosomes undergo a maturation process consisting of multiple fusions with endosomes and lysosomes, which provide an acidic environment and digestive function to the interior of the autophagosome. Here we found that a fusion protein of monomeric red-fluorescence protein and LC3, the most widely used marker for autophagosomes, exhibits a quite different localization pattern from that of GFP-LC3. GFP-LC3 loses fluorescence due to lysosomal acidic and degradative conditions but mRFP-LC3 does not, indicating that the latter can label the autophagic compartments both before and after fusion with lysosomes. Taking advantage of this property, we devised a novel method for dissecting the maturation process of autophagosomes. mRFP-GFP tandem fluorescent-tagged LC3 (tfLC3) showed a GFP and mRFP signal before the fusion with lysosomes, and exhibited only the mRFP signal subsequently. Using this method, we provided evidence that overexpression of a dominant negative form of Rab7 prevented the fusion of autophagosomes with lysosomes, suggesting that Rab7 is involved in this step. This method will be of general utility for analysis of the autophagosome maturation process.
A comparison of demethoxyviridin and wortmannin as inhibitors of phosphatidylinositol 3‐kinase (1994)

The mammalian Ptdlns 3-kinase is shown to be inhibited by low nanomolar concentrations of demethoxyviridin, an antifungal agent structurally related to wortmannin. The inhibitory potency of both compounds could be observed in purified Ptdlns 3-kinase whether or not the regulatory subunit (p85 alpha) was present, suggesting that the inhibitors bind to the catalytic subunit (p110) of the Ptdlns 3-kinase. These inhibitors also show similar potency against the intrinsic p85-phosphorylating activity of the p110-kinase. However, the structurally related Ptdlns 3-kinase from Saccharomyces cerevisiae (Vps34p) is not inhibited by either compound. Both inhibitors target the mammalian Ptdlns 3-kinase in vitro and in vivo, implying that these compounds should be useful in suppressing Ptdlns 3-kinase in mammalian systems. The inhibitors did not affect the mammalian Ptdlns 4-kinase, but they are able to inhibit a membrane-associated Ptdlns 4-kinase from Schizosaccharomyces pombe.