gebhart/patrepeval huggingface dataset:
Combinatorial chromatin modification patterns in the human genome revealed by subspace clustering (2011)

Chromatin modifications, such as post-translational modification of histone proteins and incorporation of histone variants, play an important role in regulating gene expression. Joint analyses of multiple histone modification maps are starting to reveal combinatorial patterns of modifications that are associated with functional DNA elements, providing support to the 'histone code' hypothesis. However, due to the lack of analytical methods, only a small number of chromatin modification patterns have been discovered so far. Here, we introduce a scalable subspace clustering algorithm, coherent and shifted bicluster identification (CoSBI), to exhaustively identify the set of combinatorial modification patterns across a given epigenome. Performance comparisons demonstrate that CoSBI can generate biclusters with higher intra-cluster coherency and biological relevance. We apply our algorithm to a compendium of 39 genome-wide chromatin modification maps in human CD4(+) T cells. We identify 843 combinatorial patterns that recur at >0.1% of the genome. A total of 19 chromatin modifications are observed in the combinatorial patterns, 10 of which occur in more than half of the patterns. We also identify combinatorial modification signatures for eight classes of functional DNA elements. Application of CoSBI to epigenome maps of different cells and developmental stages will aid in understanding how chromatin structure helps regulate gene expression.
Refractive-index profiling of graded-index planar waveguides from effective indexes measured for both mode types and at different wavelengths (1996)

It is well known that, under the WKB approximation, the refractive-index profile of a graded-index planar waveguide can be calculated from the corresponding effective-index function, which can be found approximately by least-squares fitting of a set of measured effective indexes. In the previous work, effective indexes measured for a particular type of modes (the TE or TM modes) at a single wavelength are used. This requires that the waveguide supports at least three modes of the same type. In this paper, techniques of combining the effective indexes measured for both mode types and at different wavelengths are proposed and demonstrated with examples. With these techniques, single-mode and two-mode waveguides can be profiled.
Uncoupling PR Gene Expression from NPR1 and Bacterial Resistance: Characterization of the Dominant Arabidopsis cpr6-1 Mutant (1998)

In Arabidopsis, NPR1 mediates the salicylic acid (SA)-induced expression of pathogenesis-related (PR) genes and systemic acquired resistance (SAR). Here, we report the identification of another component, CPR 6, that may function with NPR1 in regulating PR gene expression. The dominant CPR 6-1 mutant expresses the SA/NPR1-regulated PR genes (PR-1, BGL 2, and PR-5) and displays enhanced resistance to Pseudomonas syringae pv maculicola ES4326 and Peronospora parasitica Noco2 in the absence of SAR induction. cpr 6-1-induced PR gene expression is not suppressed in the cpr 6-1 npr1-1 double mutant but is suppressed when SA is removed by salicylate hydroxylase. Thus, constitutive PR gene expression in cpr 6-1 requires SA but not NPR1. In addition, resistance to P. s. maculicola ES4326 is suppressed in the cpr 6-1 npr1-1 double mutant, despite expression of PR-1, BGL 2, and PR-5. Resistance to P. s. maculicola ES4326 must therefore be accomplished through unidentified antibacterial gene products that are regulated through NPR1. These results show that CPR 6 is an important regulator of multiple signal transduction pathways involved in plant defense.
A porous metal system for joint replacement surgery. (1978)

A porous coated chrome cobalt system has been developed to provide long term stabilization in joint replacement surgery. The pore sizes are 50 to 100 microns, thus ensuring sufficient fatigue strength for use in high load bearing situations. Extensive in vitro and in vivo studies have been performed, and a five year follow-up of porous coated total shoulder prostheses has failed to reveal any evidence of loosening. The early results of porous coated hip implants is encouraging.
Combined Treatment of γ-Tocotrienol with Statins Induce Mammary Tumor Cell Cycle Arrest in G1 (2009)

Statins and gamma-tocotrienol (a rare isoform of vitamin E) both inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase activity and display anticancer activity. However, clinical application of statins has been limited by high dose toxicity. Previous studies showed that combined statin and gamma-tocotrienol treatment synergistically inhibits growth of highly malignant +SA mammary epithelial cells in culture. To investigate the mechanism mediating this growth inhibition, studies were conducted to determine the effect of combination low dose gamma-tocotrienol and statin treatment on +SA mammary tumor cell cycle progression. Treatment with 0.25 microM simvastatin, lovastatin, mevastatin, 10 microM pravastatin or 2.0 microM gamma-tocotrienol alone had no effect, while combined treatment of individual statins with gamma-tocotrienol significantly inhibited +SA cell proliferation during the 4-day culture period. Flow cytometric analysis demonstrated that combined treatment induced cell cycle arrest in G1. Additional studies showed that treatment with 0.25 microM simvastatin or 2 microM gamma-tocotrienol alone had no effect on the relative intracellular levels of cyclin D1, CDK2, CDK4 and CDK6, but combined treatment caused a large reduction in cyclin D1 and CDK2 levels. Combined treatments also caused a relatively large increase in p27, but had no effect on p21 and p15 levels, and resulted in a large reduction in retinoblastoma (Rb) protein phosphorylation at ser780 and ser807/811. Similar effects were observed following combined treatment of gamma-tocotrienol with low doses of lovastatin, mevastatin and pravastatin. These findings demonstrate that combination low dose statin and gamma-tocotrienol treatment induced mammary tumor cell cycle arrest at G1, resulting from an increase in p27 expression, and a corresponding decrease in cyclin D1, CDK2, and hypophosphorylation of Rb protein. These findings suggest that combined treatment of statins with gamma-tocotrienol may provide significant health benefits in the treatment of breast cancer in women, while avoiding myotoxicity associated with high dose statin monotherapy.
Probiotics, beneficial bacteria, and inflammatory bowel disease – What do we actually know? (2009)

Despite the common use of probiotics in bowel disorders, little is known about the mechanisms by which probiotics produce a beneficial effect. The clear identification of antigens and the immune cells that they interact with still remain to be discovered. The recent discovery of the anti-inflammatory effects of Bacteriodes fragilis has revealed a new concept of polysaccharide antigen presentation on antigen presenting cells. It has been found that polysaccharide A (PSA), produced by B. fragilis, interacts with antigen presenting cells and T-cells to modulate a potent anti-inflammatory response. The aim of this paper is to briefly summarize the mechanisms by which a specific probiotic organism, Lactobacilus rhamnosus GG, and the bacterium B. fragilis exert their beneficial effects while elucidating areas that need more study.
Specific Oncogenic Activity of the Src-Family Tyrosine Kinase c-Yes in Colon Carcinoma Cells (2011)

c-Yes, a member of the Src tyrosine kinase family, is found highly activated in colon carcinoma but its importance relative to c-Src has remained unclear. Here we show that, in HT29 colon carcinoma cells, silencing of c-Yes, but not of c-Src, selectively leads to an increase of cell clustering associated with a localisation of β-catenin at cell membranes and a reduction of expression of β-catenin target genes. c-Yes silencing induced an increase in apoptosis, inhibition of growth in soft-agar and in mouse xenografts, inhibition of cell migration and loss of the capacity to generate liver metastases in mice. Re-introduction of c-Yes, but not c -Src, restores transforming properties of c-Yes depleted cells. Moreover, we found that c-Yes kinase activity is required for its role in β-catenin localisation and growth in soft agar, whereas kinase activity is dispensable for its role in cell migration. We conclude that c-Yes regulates specific oncogenic signalling pathways important for colon cancer progression that is not shared with c-Src.
Detection of Heavy Metal Ions at Femtomolar Levels Using Protein-Based Biosensors (1998)

Sensors based on proteins (GST-SmtA and MerR) with distinct binding sites for heavy metal ions were developed and characterized. A capacitive signal transducer was used to measure the conformational change following binding. The proteins were overexpressed in Escherichia coli, purified, and immobilized in different ways to a self-assembled thiol layer on a gold electrode placed as the working electrode in a potentiostatic arrangement in a flow analysis system. The selectivity and the sensitivity of the two protein-based biosensors were measured and compared for copper, cadmium, mercury, and zinc ions. The GST-SmtA electrodes displayed a broader selectivity (sensing all four heavy metal ions) compared with the MerR-based ones, which showed an accentuated selectivity for mercury ions. Metal ions could be detected with both electrode types down to femtomolar concentration. The upper measuring limits, presumably due to near saturation of the proteins' binding sites, were around 10(-10) M. Control electrodes similarly constructed but based on bovine serum albumin or urease did not yield any signals. The electrodes could be regenerated with EDTA and used for more than 2 weeks with about 40% reduction in sensitivity.
Fluorescent Chemosensors Based on Energy Migration in Conjugated Polymers: The Molecular Wire Approach to Increased Sensitivity (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFluorescent Chemosensors Based on Energy Migration in Conjugated Polymers: The Molecular Wire Approach to Increased SensitivityQin Zhou and Timothy M. SwagerCite this: J. Am. Chem. Soc. 1995, 117, 50, 12593–12602Publication Date (Print):December 1, 1995Publication History Published online1 May 2002Published inissue 1 December 1995https://pubs.acs.org/doi/10.1021/ja00155a023https://doi.org/10.1021/ja00155a023research-articleACS PublicationsRequest reuse permissionsArticle Views5010Altmetric-Citations622LEARN 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
Efficacy of transferrin‐conjugated paclitaxel‐loaded nanoparticles in a murine model of prostate cancer (2004)

Chemotherapy remains the preferred choice of treatment for prostate cancer but modest drug response and significant toxicity by conventional methods of administration limit their efficacy. In our study, we determined the efficacy of paclitaxel (Tx)-loaded biodegradable nanoparticles (NPs) on tumor inhibition. We hypothesized that NPs following conjugation to transferrin (Tf) ligand (NPs-Tf) would enhance the therapeutic efficacy of the encapsulated drug. The antiproliferative activity of NPs was determined in human prostate cancer cell line (PC3) and their effect on tumor inhibition in a murine model of prostate cancer. NPs (approximately 220 nm in diameter, 5.4% w/w drug loading) under in vitro conditions exhibited sustained release of the encapsulated drug (60% release in 60 days). The IC50 (concentration of drug for 50% inhibition of cell growth) of the drug with Tf-conjugated NPs (Tx-NPs-Tf) was about 5-fold lower than that with unconjugated NPs (Tx-NPs) or drug in solution. Animals that received a single-dose intratumoral injection of Tx-NPs-Tf (Tx dose= 4 mg/kg) demonstrated complete tumor regression and greater survival rate than those that received either Tx-NPs or Tx-Cremophor EL formulation. In conclusion, sustained release NPs demonstrated greater antitumor activity following their conjugation to Tf ligand.
Effect of the efflux pump inhibitor Phe-Arg- -naphthylamide on the MIC values of the quinolones, tetracycline and chloramphenicol, in Escherichia coli isolates of different origin (2004)

Sir, The main mechanisms of quinolone resistance in Escherichia coli include mutations in the gyrA and parC target genes and decreased intracellular accumulation.1 Active efflux pumps are important for intrinsic and acquired antibiotic resistance, and overexpression of efflux pumps affecting quinolones is becoming increasingly common in E. coli. Recently, efflux pump inhibitors have been investigated with a view to improving and potentiating the activity of exported antibiotics.2 Phe-Arg-β-naphthylamide has been described as a broad-spectrum efflux pump inhibitor in Pseudomonas aeruginosa.2 The effect of this inhibitor on fluoroquinolone susceptibilities in Enterobacter aerogenes,3 E. coli,4 P. aeruginosa,2 Acinetobacter baumannii5 and Stenotrophomonas maltophilia5 has also been studied, but not for nalidixic acid and other antimicrobial agents in E. coli. Therefore in this study, we analysed the influence of the Phe-Arg-β-naphthylamide (Sigma) inhibitor on the activity of quinolones, chloramphenicol and tetracycline against a collection of 60 E. coli isolates previously characterized with respect to amino acid changes in both GyrA and ParC proteins.6,7 The collection includes the strain Nor5, an in vitro selected quinolone-resistant mutant, in which the overexpression of MarA, SoxS and AcrA has been shown (J. Vila, B. Peter, J. Sanchez-Cespedes & M. Tario, unpublished data). The remaining 59 isolates were recovered from foods (n = 11), humans (n = 25) and animals (n = 23). Susceptibilities to nalidixic acid, norfloxacin, chloramphenicol, tetracycline and ciprofloxacin were studied by agar dilution in the presence or absence of 20 mg/L of Phe-Arg-β-naphthylamide, in accordance with NCCLS guidelines. All of the 60 E. coli isolates showed an MIC value of >256 mg/L to Phe-Arg-β-naphthylamide. Table 1 shows the effect of 20 mg/L of the inhibitor Phe-Arg-β-naphthylamide on the MIC values of the five tested antibiotics in 60 E. coli isolates with different numbers of amino acid changes in GyrA and T ab le 1 . M IC v al ue s (i n m g/ L ) of th e fi ve te st ed a nt ib io tic s in th e pr es en ce o r ab se nc e of 2 0 m g/ L o f P he -A rg β -n ap ht hy la m id e in a s er ie s of 6 0 E . c ol i i so la te s or ga ni ze d
A new algorithm for adaptive arrays (1987)

A new deflected stochastic-gradient algorithm for adaptive sensor arrays is introduced. It is shown to have the capability of converging substantially faster than the nondeflected stochastic gradient (LMS) algorithm but slower than the recursive least squares (RLS) algorithm. Because of its amenability to reduction of computational complexity by data quantization, it has the potential for processing digital signals with bandwidths one to two orders of magnitude larger than the bandwidths manageable with the RLS algorithm for sensor arrays containing a number of adjustable weights in the approximate range of 10-50.
Optimization of Commingled Production using Infinitely Variable Inflow Control Valves (2004)

Abstract We developed an operational strategy for commingled production with infinitely variable Inflow Control Valves (ICVs) using sequential linear programming. The optimization algorithm requires instantaneous and derivative information. We propose a workflow where the production engineer relies on measurements to determine the flow rate and pressure values, and on models to determine the derivative information, i.e. the changes in flow rates as a result of a change in an ICV setting. Such a model would typically be a steady-state well bore simulator including choke models to represent the ICVs and inflow models to represent the near-well reservoir flow in the various zones. The parameters of the model need to be updated regularly using real-time measurements and production tests, and we discuss the impact of different smart well instrumentation levels on the updating process. We simulated the performance of this production optimization strategy in a reservoir simulator. Some numerical aspects of the algorithm and problems encountered during implementation are discussed. The performance of the algorithm was tested in two reservoir settings. In both cases, the optimization resulted in accelerated oil production compared to conventional, surface controlled, production. However, accelerated production did not always result in higher ultimate recovery compared to the conventional case. In such situations the benefits of either short-term production optimization (accelerating production) or long-term reservoir management (maximizing recovery) should be weighed.
Iron Oxide @ Polypyrrole Nanoparticles as a Multifunctional Drug Carrier for Remotely Controlled Cancer Therapy with Synergistic Antitumor Effect (2013)

Multifunctional nanoplatforms that are safe and have multiple therapeutic functions together with imaging capabilities are highly demanded in the development of new cancer theranostic approaches. A number of near-infrared (NIR)-absorbing inorganic nanomaterials, although having shown great promise not only to photothermally ablate tumors but also to enhance the efficacy of other types of therapies, are not biodegradable and would be retained in the body for a long time. Herein, we develop a multifunctional nanocomposite by coating magnetic iron oxide nanoclusters with a near-infrared light-absorbing polymer polypyrrole (PPy), obtaining Fe3O4@PPy core-shell nanoparticles, which after functionalization with polyethylene glycol could be used for imaging-guided, remotely controlled cancer combination therapy. In this system, the Fe3O4 core, which could be gradually decomposed in physiological environments, is useful for magnetically controlled drug delivery as well as a magnetic resonance imaging contrast. The PPy shell, as an organic polymer, is able to load therapeutic molecules with aromatic structures and also exhibits a strong photothermal effect, which can be used to enhance the chemotherapeutic efficacy, showing an outstanding in vivo synergistic antitumor effect. Our work encourages further exploration of light-absorbing polymer-based nanocomposites for cancer combination therapy under remote physical controls.
Purification and characterization of protein disulphide-isomerase from the unicellular green alga Chlamydomonas reinhardii. A 120 kDa dimer antigenically distinct from the vertebrate enzyme (1990)

Protein disulphide-isomerase (PDI) has been isolated from the unicellular green alga Chlamydomonas reinhardii and purified by (NH4)2SO4 precipitation, gel filtration and DEAE-Sephacel, hydroxyapatite and f.p.l.c. chromatography. The active algal enzyme is a 120 kDa dimer with a subunit molecular mass of 60 kDa when determined by SDS/PAGE. Although similar in size to the previously isolated vertebrate PDIs, the algal enzyme is antigenically distinct, polyclonal antibodies against the algal PDI showing no cross-reactivity with the vertebrate enzyme on immunoblots, and vice versa. The anti-(algal PDI) antiserum did not inhibit algal PDI activity, and C. reinhardii PDI could be immobilized on anti-PDI-Protein A-Sepharose in active form. In contrast with the situation in vertebrates, where PDI functions as a subunit of prolyl 4-hydroxylase, the C. reinhardii PDI is not associated with the algal prolyl 4-hydroxylase.
Presence of a High Amount of Stroma and Downregulation of SMAD4 Predict for Worse Survival for Stage I–II Colon Cancer Patients (2009)

Background : For stage I–II colon cancer a significant number (5–25%) of patients has recurrent disease within 5 years. There is need to identify these high-risk patients as they might benefit from additional treatment. Stroma-tissue surrounding the cancer cells plays an important role in the tumor behavior. The proportion of intra-tumor stroma was evaluated for the identification of high-risk patients. In addition, protein expression of markers involved in pathways related to stroma production and epithelial-to-mesenchymal transition (EMT) was analyzed: β -catenin, TGF- β -R2 and SMAD4. Methods : In a retrospective study of 135 patients with stage I–II colon cancer, the amount of stroma was estimated on routine haematoxylin–eosin stained histological sections. Sections were also immunohistochemically stained for β -catenin, TGF- β -R2 and SMAD4. Results : Of 135 analyzed patients 34 (25.2%) showed a high proportion of stroma (stroma-high) and 101 (74.8%) a low proportion (stroma-low). Significant differences in overall-survival and disease-free-survival were observed between the two groups, with stroma-high patients showing poor survival (OS p &lt; 0.001, HZ 2.73, CI 1.73–4.30; DFS p &lt; 0.001, HZ 2.43, CI 1.55–3.82). A high-risk group was identified with stroma-high and SMAD4 loss (OS p = 0.008, HZ 7.98, CI 4.12–15.44, DFS p = 0.005, HZ 6.57, CI 3.43–12.56); 12 of 14 (85.7%) patients died within 3 years. In a logistic-regression analysis a high proportion of stroma and SMAD4 loss were strongly related (HZ 5.42, CI 2.13–13.82, p &lt; 0.001). Conclusion : Conventional haematoxylin–eosin stained tumor slides contain more prognostic information than previously fathomed. This can be unleashed by assessing the tumor–stroma ratio. The combination of analyzing the tumor–stroma ratio and staining for SMAD4 results in an independent parameter for confident prediction of clinical outcome.
Illuminating the reaction pathway of the FokI restriction endonuclease by fluorescence resonance energy transfer (2011)

The FokI restriction endonuclease is a monomeric protein that recognizes an asymmetric sequence and cleaves both DNA strands at fixed loci downstream of the site. Its single active site is positioned initially near the recognition sequence, distant from its downstream target 13 nucleotides away. Moreover, to cut both strands, it has to recruit a second monomer to give an assembly with two active sites. Here, the individual steps in the FokI reaction pathway were examined by fluorescence resonance energy transfer (FRET). To monitor DNA binding and domain motion, a fluorescence donor was attached to the DNA, either downstream or upstream of the recognition site, and an acceptor placed on the catalytic domain of the protein. A FokI variant incapable of dimerization was also employed, to disentangle the signal due to domain motion from that due to protein association. Dimerization was monitored separately by using two samples of FokI labelled with donor and acceptor, respectively. The stopped-flow studies revealed a complete reaction pathway for FokI, both the sequence of events and the kinetics of each individual step.