gebhart/patrepeval huggingface dataset:
Rational protein design: Combining theory and experiment (1997)

The rational design of protein structure and function is rapidly emerging as a powerful approach to test general theories in protein chemistry (1). De novo creation of a protein or an active site requires that all the necessary interactions are provided. The design approach is therefore a way to test the limits of completeness of understanding experimentally. Furthermore, if the experiments are devised in a progressive fashion, such that the simplest possible designs are tried first, followed by iterative additions of more complex interactions until the desired result is achieved, then it may be possible to identify a minimally sufficient set of components. At the center of the design approach is the “design cycle,” in which theory and experiment alternate. The starting point is the development of a molecular model, based on rules of protein structure and function, combined with an algorithm for applying these. This is followed by experimental construction and analysis of the properties of the designed protein. If the experimental outcome is failure or partial success, then a next iteration of the design cycle is started in which additional complexity is introduced, rules and parameters are refined, or the algorithms for applying them are modified. The paper by Dahiyat and Mayo (2) in the current issue of these Proceedings describes such a design cycle. Sequences predicted to repack the interior of a small protein were generated by a computer design algorithm using different sets of parameters describing the packing interactions, thereby establishing a direct experimental correlation between the design parameters and the properties of the resulting proteins. This work is the latest addition to a series of efforts in which objective computational techniques developed to create protein structure (3–8) or function (9, 10) are being tested directly by experiment. The ultimate goal of such …
Cancer Incidence and Mortality Trends Among Whites in the United States, 1947–84 (1987)

Cancer incidence trends from the late 1940s to 1983-84 were assessed among white residents of five geographic areas (Atlanta, Connecticut, Detroit, Iowa, San Francisco-Oakland) by means of data derived from several National Cancer Institute surveys, the Connecticut Tumor Registry, and the Surveillance, Epidemiology, and End Results Program. Incidence trends were compared with mortality trends for the entire United States and for the same five study areas. This study documented rising incidence and mortality rates for four cancers: lung cancer, melanoma of the skin, multiple myeloma, and non-Hodgkin's lymphomas. Increases in lung cancer continued through the early 1980s, but the rate of increase has been moderating during recent years, particularly among males and at younger ages for whom recent declines are evident. Overall, lung cancer incidence rates increased more than 220 and 400% among males and females, respectively. Although much rarer than lung cancer, melanoma of the skin and multiple myeloma increased greatly until the early 1980s among both males and females. The overall rate of increase in melanoma incidence among males was greater than that for lung cancer, and the rate of increase in multiple myeloma mortality among females was exceeded only by that for lung cancer. Increases of 70-120% were observed for non-Hodgkin's lymphomas. Increases in incidence and mortality rates for pancreatic cancer were apparent during the early years but less conspicuous in recent years. Laryngeal and kidney cancer rates generally increased substantially, although the changes were not remarkable for laryngeal cancer mortality among males and kidney cancer mortality among females. The rates for cancers of the mouth and pharynx increased among females but not males. Prostate, colon, and bladder cancer incidence rates increased more than 65% among males, whereas mortality rates changed only moderately. The incidence of thyroid cancer increased more than 75% among both sexes until the late 1970s, but mortality rates have declined during the period of study. Breast cancer incidence increased 30%, whereas mortality rates remained remarkably constant. The incidence of corpus uteri cancer increased dramatically during the mid-1970s and decreased substantially thereafter; these changes were not reflected in the mortality rates, which continually declined during the entire time period. The incidence of testicular cancer increased more than 90% and that of Hodgkin's disease did not change greatly; however, mortality rates for both cancers declined more than 50% since the late 1960s and early 1970s.(ABSTRACT TRUNCATED AT 400 WORDS)
Circular permutation and receptor insertion within green fluorescent proteins (1999)

Many areas of biology and biotechnology have been revolutionized by the ability to label proteins genetically by fusion to the Aequorea green fluorescent protein (GFP). In previous fusions, the GFP has been treated as an indivisible entity, usually appended to the amino or carboxyl terminus of the host protein, occasionally inserted within the host sequence. The tightly interwoven, three-dimensional structure and intricate posttranslational self-modification required for chromophore formation would suggest that major rearrangements or insertions within GFP would prevent fluorescence. However, we now show that several rearrangements of GFPs, in which the amino and carboxyl portions are interchanged and rejoined with a short spacer connecting the original termini, still become fluorescent. These circular permutations have altered pKa values and orientations of the chromophore with respect to a fusion partner. Furthermore, certain locations within GFP tolerate insertion of entire proteins, and conformational changes in the insert can have profound effects on the fluorescence. For example, insertions of calmodulin or a zinc finger domain in place of Tyr-145 of a yellow mutant (enhanced yellow fluorescent protein) of GFP result in indicator proteins whose fluorescence can be enhanced severalfold upon metal binding. The calmodulin graft into enhanced yellow fluorescent protein can monitor cytosolic Ca(2+) in single mammalian cells. The tolerance of GFPs for circular permutations and insertions shows the folding process is surprisingly robust and offers a new strategy for creating genetically encodable, physiological indicators.
RNA : protein interactions : a practical approach (1998)

Applications of chemically-synthesized RNA preparation of RNA-protein complexes for x-ray crystallography and NMR uses of site-specifically modified RNAs constructed by RNA ligation the electrophoretic mobility shift assay for RNA binding proteins affinity methods for isolating RNA-binding proteins synthetic lethal/enhancer screening to identify snRNA-protein and protein-protein interactions in yeast pre-mRNA splicing detecting RNA-protein interactions and isolating cDNA clones by northwestern screening a three-hybrid system to detect and analyze RNA-protein interactions in vivo in-vivo selection of specific RNA-binding polypeptides using a transcription anti-termination reporter assay foot-printing and modification-interference analysis of binding sites on RNA analysis of RNA-protein and RNA-RNA contacts between ribosomes and functional ligands using site-directed cross-linking techniques in-vitro selection of nucleic acid ligands.
Heparanase and Platelet Factor-4 Induce Smooth Muscle Cell Proliferation and Migration via bFGF Release from the ECM (2002)

Basic fibroblast growth factor (bFGF) has been shown to play an instrumental role in the cascade of events leading to restenosis; however, the mechanisms of bFGF activation following vascular injury have remained elusive. We have demonstrated that heparanase and platelet factor-4 (PF4), released from activated platelets at the site of injury, liberate bFGF from the extracellular matrix (ECM) of vascular smooth muscle cells (SMC), resulting in the induction of SMC proliferation and migration. Increases in proliferation and migration were inhibited by treatment with a bFGF-neutralizing antibody, suggesting that proliferation and migration in response to heparanase or PF4 are mediated by bFGF activation. When platelets were seeded on top of SMCs, degranulation products were found to release bFGF from the ECM, increasing cell proliferation and cell migration. Again, these increases in SMC proliferation and migration were inhibited by treatment with an anti-bFGF antibody. Furthermore, these increases in proliferation were completely inhibited by treatment with an anti-heparanase antibody. Platelet degranulation products, such as heparanase and PF4, may liberate bFGF from extracellular sequestration, activating the growth factor and inducing the SMC proliferation and migration that contribute to the wound healing response following vascular injury.
Involvement of Mortalin in Cellular Senescence from the Perspective of its Mitochondrial Import, Chaperone, and Oxidative Stress Management Functions (2007)

Mortalin (mtHSP70/GRP75) is a heat uninducible member of hsp70 family of proteins. Some of the established features of mortalin include its various subcellular sites, multiple binding partners, and differential subcellular distribution in normal and immortal cells. Overexpression of mortalin leads to extended life span in nematode and normal human cells. On the other hand, it serves as a major target for oxidation and was shown to be involved in old age pathologies including Parkinson's and Alzheimer's disease. Since mortalin interacts with many proteins, its modifications in response to stress and damage caused by intracellular oxidation are likely to generate pleiotropic effects. For example, (a) inefficient import of mitochondrial proteins by mortalin-Tim complexes may result into inefficient mitochondrial genesis, energy generation, and functional decline and (b) inefficient chaperoning of proteins can result into a garbage catastrophe.
ChemInform Abstract: OXAZOLONES, I.‐4‐IMIDAZOLIN‐2‐ONES BY REARRANGEMENT OF 2‐OXO‐4‐OXAZOLINE‐3‐CARBOXAMIDES (1976)

Abstract Die aus den Oxazolinonen (Ia) und den entsprechenden Isocyanaten erhältlichen Carboxamide (IIa) lagem sich beim Erhitzen in einem Gemisch von Essigsäure und konz. Bromwasserstoffsäure oder in konz. Salzsäure unter Ringspaltung, COQ‐Abspaltung und Recyclisierung in die Imidazolinone (IIIa) um.
Loss of tumor suppressor KDM6A amplifies PRC2-regulated transcriptional repression in bladder cancer and can be targeted through inhibition of EZH2 (2017)

Trithorax-like group complex containing KDM6A acts antagonistically to Polycomb-repressive complex 2 (PRC2) containing EZH2 in maintaining the dynamics of the repression and activation of gene expression through H3K27 methylation. In urothelial bladder carcinoma, <i>KDM6A</i> (a H3K27 demethylase) is frequently mutated, but its functional consequences and therapeutic targetability remain unknown. About 70% of <i>KDM6A</i> mutations resulted in a total loss of expression and a consequent loss of demethylase function in this cancer type. Further transcriptome analysis found multiple deregulated pathways, especially PRC2/EZH2, in <i>KDM6A</i>-mutated urothelial bladder carcinoma. Chromatin immunoprecipitation sequencing analysis revealed enrichment of H3K27me3 at specific loci in <i>KDM6A</i>-null cells, including PRC2/EZH2 and their downstream targets. Consequently, we targeted EZH2 (an H3K27 methylase) and demonstrated that <i>KDM6A</i>-null urothelial bladder carcinoma cell lines were sensitive to EZH2 inhibition. Loss- and gain-of-function assays confirmed that cells with loss of KDM6A are vulnerable to EZH2. IGFBP3, a direct KDM6A/EZH2/H3K27me3 target, was up-regulated by EZH2 inhibition and contributed to the observed EZH2-dependent growth suppression in <i>KDM6A</i>-null cell lines. EZH2 inhibition delayed tumor onset in <i>KDM6A</i>-null cells and caused regression of <i>KDM6A</i>-null bladder tumors in both patient-derived and cell line xenograft models. In summary, our study demonstrates that inactivating mutations of <i>KDM6A</i>, which are common in urothelial bladder carcinoma, are potentially targetable by inhibiting EZH2.
Customizing the Fatty Acid Content of Broiler Tissues (1991)

Safflower (79% linoleic acid), olive (70% oleic acid), and coconut (83% saturated fatty acids) oils were each fed to broilers at 8% of the diet to evaluate the possibility of enriching the levels of specific fatty acids in broiler breast and adipose tissues but not affecting the tissue proximate composition or cholesterol content. Levels of the predominate fatty acid of each dietary oil were elevated in both tissues with the increase being more pronounced in the adipose tissue. Differences in saturated acid:oleic acid:linoleic acid ratios in the breast and adipose tissues reflected the differences in these ratios in the dietary oils (safflower 8:13:79, olive 13:70:12, coconut 83:7:2). Slight changes were detected in moisture and cholesterol contents of breast muscle due to dietary oil. These results suggest a means for broiler producers to improve the consumer appeal of broiler meat in view of concern about human intake of saturated and polyunsaturated fatty acids.
Differences in crystal properties and ligand affinities of an antifluorescyl fab (4‐4‐20) in two solvent systems (1988)

An antigen-binding fragment (Fab) from a murine monoclonal antibody (4-4-20) with high affinity for fluorescein was cocrystallized with ligand in polyethylene glycol (PEG) and 2-methyl-2,4-pentanediol (MPD) in forms suitable for X-ray analyses. In MPD the affinity of the intact antibody for fluorescein was 300 times lower than the value (3.4 x 10(10) M-1) obtained in aqueous buffers. This decreased affinity was manifested by the partial release of bound fluorescein when MPD was added to solutions of liganded Fab during crystallization trials. In PEG, the ligand remained firmly bound to the protein. The liganded Fab crystallized in the monoclinic space group P2(1) in PEG, with a = 58.6, b = 97.2, c = 44.5 A and beta = 95.2 degrees. In MPD the space group was triclinic P1, with a = 58.3, b = 43.4, c = 42.3 A, alpha = 83.9 degrees, beta = 87.6 degrees, and gamma = 84.5 degrees. X-ray diffraction data were collected for both forms to 2.5-A resolution. Surprisingly, the triclinic form of the liganed antifluorescyl Fab had the same space group, closely similar cell dimensions, and practically the same orientation in the unit cell as an unliganded Fab (BV04-01) with activity against single-stranded DNA.
Tension-free vaginal tape and percutaneous vaginal tape sling procedures. (2001)

Preliminary reports and the experience at our institution suggest that the techniques of midurethral synthetic sling placement of TVT and PVT are reproducible, easy to master, and minimally invasive with respect to tissue handling. Although complications with all anti-incontinence procedures exist, understanding the anatomical considerations and methodology of these unique procedures should minimize patient morbidity, avoid patient mortality, and produce a high rate of durable success.
Analysis of Neutrophil Polarization and Chemotaxis (2007)

Neutrophil polarization and directed migration (chemotaxis) are critical for the inflammatory response. Neutrophil chemotaxis is achieved by the sensing of narrow gradients of chemoattractant and the subsequent polarization and directed migration toward the chemotactic source. Despite recent progress, the signaling mechanisms that regulate neutrophil polarization during chemotaxis have not been clearly defined. Here, we describe methods to analyze neutrophil polarization and asymmetric redistribution of signaling components induced by chemoattractant using immunofluorescence. Further, methods are described to dissect the role of specific signaling pathways during chemotaxis by the use of murine neutrophils from transgenic mouse models. Finally, methods for time-lapse microscopy and transwell assay for the analysis of neutrophil chemotaxis will also be discussed.
Revisitation patterns in World Wide Web navigation (1997)

Article Free Access Share on Revisitation patterns in World Wide Web navigation Authors: Linda Tauscher Department of Computer Science, University of Calgary, Calgary, Alberta, Canada T2N 1N4 Department of Computer Science, University of Calgary, Calgary, Alberta, Canada T2N 1N4View Profile , Saul Greenberg Department of Computer Science, University of Calgary, Calgary, Alberta, Canada T2N 1N4 Department of Computer Science, University of Calgary, Calgary, Alberta, Canada T2N 1N4View Profile Authors Info & Claims CHI '97: Proceedings of the ACM SIGCHI Conference on Human factors in computing systemsMarch 1997 Pages 399–406https://doi.org/10.1145/258549.258816Published:27 March 1997Publication History 115citation1,602DownloadsMetricsTotal Citations115Total Downloads1,602Last 12 Months60Last 6 weeks11 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 Alerts New Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Antioxidant Activity of Natural Products against Aluminium Fluoride Induced Oxidative Stress (2013)

Evaluation of antioxidant potential of natural products against Aluminium fluoride (AlF4) induced oxidative stress in albino mice were represented in the present study. Gossypin, Quercetin dehydrate, (-)-Epicatechin gallate, Gallic acid and Suramin sulphate (G-protein inhibitor) were evaluated for antioxidant activity by measuring various biochemical / enzymatic markers such as lipid peroxidation, glutathione, total thiols, catalase and superoxide dismutase. Exposure to Aluminium fluoride resulted in the oxidative stress and free radical mediated damage. The flavonoids like Gossypin, Quercetin, (-) -Epicatechin gallate, Gallic acid and Suramin sulphate are significantly reduced lipid peroxidation, reversed the reduced protective enzymes SOD,CAT and non-enzymatic like glutathione and total thiols levels were approached to normal levels in Aluminium fluoride exposed mice. All the test compounds were showed significant protectionagainst fluoride toxicity. Results of the present study reveals that the flavonoids and Suramin sulphate showed significant antioxidant activity on Aluminium fluoride induced oxidative stress. Further research warranted to study their exact mechanism of action.
Properties of a panel of monoclonal antibodies which react with the human T cell antigen receptor on the leukemic line HPB-ALL and a subset of normal peripheral blood T lymphocytes. (1986)

Five Mab raised against the T cell antigen receptor of the human T cell line HPB-ALL which react with a subpopulation of normal peripheral blood T cells are described. Three Mab, 3D6, 1C1, and 1C2, react with 3 to 5% of normal PBL and stimulate proliferation of the cells with which they react. An increase in the number of cells which react with all five Mab occurs. Two Mab, 2D4 and 65, react with subsets of the cells which bind 1C1, 1C2, and 3D6 and divide the family into four subgroups, 2D4+ 65+, 2D4+ 65-, 2D4- 65+, and 2D4- 65-. Functional T cell clones in all four subfamilies have been observed. Cytolytic function can be correlated with the TcR phenotype expressed because all of the Mab which react with a particular clone inhibit its ability to lyse a specific target. The epitopes recognized by the panel are closely related because all five block each other's binding to HPB-ALL. In addition, the determinants recognized by 3D6, 1C1, and 1C2 on normal lymphocytes are probably very closely related because all clones examined react with all three Mab.
System-Level Analysis of Neuroblastoma Tumor–Initiating Cells Implicates AURKB as a Novel Drug Target for Neuroblastoma (2010)

This work provides the first high-resolution system-level analysis of the transcriptomes of 11 primary human NB TICs and identifies a set of candidate NB TIC-enriched transcripts for further development as therapeutic targets.
Economic dispatch in microgrids using multi-agent system (2012)

In traditional bulk power system, economic dispatch is usually conducted in a central controller, which has access to global system information. However, characterized as flexible and “plug and play”, microgrids are often controlled in a distributed manner. This paper presents a decentralized architecture of multi-agent system for economic dispatch of distributed generators (DG) in microgrids. In this architecture, all DGs are equipped with identical agents, which can only perceive local information or obtain necessary information from their neighbors. By competing with each other, agents attempt to maximize their own profit, thereby tending to an optimal global solution. This paper first develops necessary conditions for minimal cost operation of microgrids. Then it proposes an innovative multi-agent communication algorithm to implement the minimal principle in multi-agent environment based on the consensus theorem. In the end, a five-agent system and a fifty-agent system are investigated to validate the proposed multi-agent algorithm.
Invited review: Amino acid bioavailability and digestibility in pig feed ingredients: Terminology and application (2006)

In this review, the terminology that is used to describe the bioavailability and ileal digestibility of AA in pig feed ingredients is defined. Aspects of the methodology to establish bioavailability and ileal digestibility values also are discussed, and recommendations about the use of these values are provided. Two main factors can contribute to differences between bioavailability and ileal digestibility of AA. First, some AA, such as Lys, may be absorbed in chemical complexes that preclude their use for metabolism. Second, fermentation in the upper gut may result in a net loss or gain of AA to the animal. In addition, dietary effects on the efficiency of using bioavailable AA intake for tissue growth or milk production should be considered and may be attributed to endogenous AA losses in the hindgut and the metabolic costs associated with endogenous gut protein synthesis and losses. Ileal digestibility values may be expressed as apparent ileal digestibility (AID), standardized ileal digestibility (SID), or true ileal digestibility (TID). These terms are used to specify how ileal endogenous AA losses are reflected in digestibility values. Ileal endogenous AA losses may be separated into basal losses, which are not influenced by feed ingredient composition, and specific losses, which are induced by feed ingredient characteristics such as levels and types of fiber and antinutritional factors. Values for AID are established when total ileal outflow of AA (i.e., the sum of endogenous losses and nondigested dietary AA) is related to dietary AA intake. A concern with the use of AID values is that these are not additive in mixtures of feed ingredients. This concern may be overcome by correcting AID values for defined basal endogenous losses of AA, which yields SID values. Furthermore, if the AID values are corrected for basal and specific endogenous losses, then values for TID are calculated. However, reliable procedures to routinely measure specific endogenous losses are not yet available. It is recommended that basal ileal endogenous losses of AA should be measured in digestibility experiments using a defined protein-free diet and that these losses are reported with observed AID and SID values. It is suggested that SID values should be used for feed formulation, at least until more information on TID values becomes available.