gebhart/patrepeval huggingface dataset:
A comprehensive comparison of multiple sequence alignment programs (1999)

In recent years improvements to existing programs and the introduction of new iterative algorithms have changed the state-of-the-art in protein sequence alignment. This paper presents the first systematic study of the most commonly used alignment programs using BAliBASE benchmark alignments as test cases. Even below the 'twilight zone' at 10-20% residue identity, the best programs were capable of correctly aligning on average 47% of the residues. We show that iterative algorithms often offer improved alignment accuracy though at the expense of computation time. A notable exception was the effect of introducing a single divergent sequence into a set of closely related sequences, causing the iteration to diverge away from the best alignment. Global alignment programs generally performed better than local methods, except in the presence of large N/C-terminal extensions and internal insertions. In these cases, a local algorithm was more successful in identifying the most conserved motifs. This study enables us to propose appropriate alignment strategies, depending on the nature of a particular set of sequences. The employment of more than one program based on different alignment techniques should significantly improve the quality of automatic protein sequence alignment methods. The results also indicate guidelines for improvement of alignment algorithms.
On Separate Color-Plane Prediction for Direct 4:4:4 Video Coding (2006)

In this paper, we propose a video coding scheme supporting direct 4:4:4 source format, which is designed as a straight-forward extension of MPEG-4 AVC/H.264 high profile coding. In the proposed scheme, each color component is encoded with independent spatio-temporal prediction using coding tools supported by MPEG-4 AVC/H.264 high profile, which is now regarded as the most powerful video compression standard in the world. We discuss the performance of the proposed method in comparison with several candidate schemes, and will show that the proposed scheme achieves coding performance improvement in terms of signal representation fidelity (PSNR) around higher bitrate range that is valuable for high quality applications. The presented scheme has been proposed to the MPEG-4 AVC/H.264 standardization body as a candidate technique for the new 4:4:4 video coding standard.
Blimp-1-Dependent Repression of Pax-5 Is Required for Differentiation of B Cells to Immunoglobulin M-Secreting Plasma Cells (2002)

B-cell lineage-specific activator protein (BSAP), encoded by the Pax-5 gene, is critical for B-cell lineage commitment and B-cell development but is not expressed in terminally differentiated B cells. We demonstrate a direct connection between BSAP and B-lymphocyte-induced maturation protein 1 (Blimp-1), a transcriptional repressor that is sufficient to drive plasmacytic differentiation. Blimp-1 binds a site on the Pax-5 promoter in vitro and in vivo and represses the Pax-5 promoter in a binding-site-dependent manner. By ectopically expressing Blimp-1 or a competitive inhibitor of Blimp-1, we show that Blimp-1 is both necessary and sufficient to repress Pax-5 during plasmacytic differentiation of primary splenic B cells. Blimp-1-dependent repression of Pax-5 is sufficient to regulate BSAP targets CD19 and J chain and is necessary but not sufficient to induce XBP-1. We further show that repression of Pax-5 is required for Blimp-1 to drive differentiation of splenocytes to immunoglobulin M-secreting cells. Thus, repression of Pax-5 plays a critical role in the Blimp-1-dependent program of plasmacytic differentiation.
Representation of Similarity Matrices by Trees (1967)

Abstract Suppose given a set of similarities (or dissimilarities) between pairs of of objects from some set of objects, such as animal species, books, colours. We wish to construct from this similarity matrix a tree, or nested set of clusterings of the objects; graphs of trees provide a striking visual display of similarity groupings of the objects. The construction requires (1) a definition specifying when a similarity matrix has exact tree structure, (2) a measure of distance between any two similarity matrices, which yields (when combined with (1)) a measure of distance between any similarity matrix and any tree, (3) a family of local operations on a tree, which can be used to search out trees which best fit a given similarity matrix. The construction technique is applied to voting behaviour of the 50 United States in the last 13 presidential elections, giving a tree clustering of the states.
Mutations in human O6-alkylguanine-DNA alkyltransferase imparting resistance to O6-benzylguanine. (1994)

O6-Benzylguanine is an inactivator of O6-alkylguanine-DNA alkyltransferases (AGT) which is currently entering clinical trials as an agent improving the cancer chemotherapeutic activity of chloroethylnitrosoureas and other alkylating agents. O6-Benzylguanine acts by virtue of its ability to serve as a substrate for the AGT forming S-benzylcysteine at the cysteine acceptor site. The effects of a number of mutations in the human AGT sequence on the reaction with O6-benzylguanine were investigated by two methods: (a) by measuring the loss of the ability of the AGT to repair a methylated DNA substrate after preincubation with O6-benzylguanine; and (b) by measuring the production of guanine from O6-benzylguanine by the AGT proteins. Both assays gave similar results and showed that mutations of the proline residues at positions 138 and 140 and of the glycine residue at position 156 significantly reduced the ability to react with O6-benzylguanine. The combination of these mutations gave even greater resistance. Thus, the 50% effective dose for O6-benzylguanine was increased from 0.25 microM in the control AGT to 29 microM by mutations P138K/P140A, to 60 microM by mutation G156A and to > 300 microM by mutations P140A/G156A. Truncation of the AGT at the carboxyl end, removing either 31 or 23 amino acids did not affect the activity or the ability to react with O6-benzylguanine, but removal of the 36 carboxyl terminal amino acids, which includes a highly conserved glutamic acid residue, led to the loss of all activity. The rate of the reaction between the AGT and O6-benzylguanine was increased when DNA was present. This increase amounted to about 6-fold with the control AGT and the carboxyl-truncated mutants but was reduced to only 2-fold with G156A mutant and increased to 11-18-fold with the mutations of proline residues at 138 and 140. These results indicate that several residues in the AGT sequence affect the access of the active site to O6-benzylguanine and that these residues are located in at least two regions on either side of the active site cysteine, which is located at residue 145. Mutations in these regions may occur during therapy with alkylating agents and O6-benzylguanine. The development of other AGT inactivators which are still able to inactivate the resistant mutants may be necessary to maximize the potential of AGT inhibition for cancer chemotherapy.
Carrier-Based Ion-Selective Electrodes and Bulk Optodes. 2. Ionophores for Potentiometric and Optical Sensors (1998)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCarrier-Based Ion-Selective Electrodes and Bulk Optodes. 2. Ionophores for Potentiometric and Optical SensorsPhilippe Bühlmann, Ernö Pretsch, and Eric BakkerView Author Information Department of Chemistry, School of Science, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan, Department of Organic Chemistry, Swiss Federal Institute of Technology (ETH), Universitätstrasse 16, CH-8092 Zürich, Switzerland, and Department of Chemistry, Auburn University, Auburn, Alabama 36849 Cite this: Chem. Rev. 1998, 98, 4, 1593–1688Publication Date (Web):June 4, 1998Publication History Received29 December 1997Revised8 April 1998Published online4 June 1998Published inissue 1 June 1998https://doi.org/10.1021/cr970113+Copyright © 1998 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views8347Altmetric-Citations1490LEARN 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 InReddit Read OnlinePDF (3 MB) Get e-AlertsSUBJECTS:Electrodes,Ions,Membranes,Selectivity,Sensors Get e-Alerts
Novel Combinatorial Selection of Phosphorothioate Oligonucleotide Aptamers (1998)

A novel combinatorial approach is described for construction and screening of enhanced nuclease-resistant phosphorothioate DNA "decoys" or "aptamers." Aptamers have been selected that bind tightly to the nuclear factor for human IL6 (NF-IL6), a basic leucine zipper transcription factor involved in the induction of acute-phase responsive and cytokine gene promotors in response to inflammation. Using a random combinatorial selection approach and dNTP(alphaS)'s in the PCR amplification, we can select specific thio-substituted agents which have the highest specificity in binding to target NF-IL6. Using a 22-nucleotide-long duplex random library, nanomolar binding, specific 22-mer thiophosphate backbone substitution sequences (at dA positions only) were selected. These show a different consensus sequence than normal phosphate backbone CCAAT/enhancer binding protein recognition sites for NF-IL6. Unlike the wild-type 10-mer sequences, which bind 1 protein dimer/duplex, these 22-mer thiophosphate aptamers bind with a stoichiometry of 2 dimers/duplex.
Cognitive interference alignment for OFDM two-tiered networks (2012)

In this contribution, we introduce an interference alignment scheme that allows the coexistence of an orthogonal frequency division multiplexing (OFDM) macro-cell and a cognitive small-cell, deployed in a two-tiered structure and transmitting over the same bandwidth. We derive the optimal linear strategy for the single antenna secondary base station, maximizing the spectral efficiency of the opportunistic link, accounting for both signal sub-space structure and power loading strategy. Our analytical and numerical findings prove that the precoder structure proposed is optimal for the considered scenario in the face of Rayleigh and exponential decaying channels.
Stem-Loop Binding Protein Facilitates 3′-End Formation by Stabilizing U7 snRNP Binding to Histone Pre-mRNA (1999)

The 3' end of histone mRNA is formed by an endonucleolytic cleavage of the primary transcript after a conserved stem-loop sequence. The cleavage reaction requires at least two trans-acting factors: the stem-loop binding protein (SLBP), which binds the stem-loop sequence, and the U7 snRNP that interacts with a sequence downstream from the cleavage site. Removal of SLBP from a nuclear extract abolishes 3'-end processing, and the addition of recombinant SLBP restores processing activity of the depleted extract. To determine the regions of human SLBP necessary for 3' processing, various deletion mutants of the protein were tested for their ability to complement the SLBP-depleted extract. The entire N-terminal domain and the majority of the C-terminal domain of human SLBP are dispensable for processing. The minimal protein that efficiently supports cleavage of histone pre-mRNA consists of 93 amino acids containing the 73-amino-acid RNA-binding domain and 20 amino acids located immediately next to its C terminus. Replacement of these 20 residues with an unrelated sequence in the context of the full-length SLBP reduces processing >90%. Coimmunoprecipitation experiments with the anti-SLBP antibody demonstrated that SLBP and U7 snRNP form a stable complex only in the presence of pre-mRNA substrates containing a properly positioned U7 snRNP binding site. One role of SLBP is to stabilize the interaction of the histone pre-mRNA with U7 snRNP.
Near-Infrared Fluorescent Dye-Doped Semiconducting Polymer Dots (2011)

Near-infrared (NIR) fluorescence sensing is desirable for in vivo biological measurements, but the method is currently limited by the availability of NIR fluorescent markers as well as by their poor performance, such as self-aggregation and dim fluorescence, in a physiological environment. To address this issue, this paper describes a NIR fluorescent polymer dot (Pdot) that emits at 777 nm. This Pdot was comparable in size to a water-soluble NIR quantum dot that emits at 800 nm (ITK Qdot800) but was about four times brighter and with a narrower emission peak. We formed the NIR Pdot by doping the NIR dye, silicon 2,3-naphthalocyanine bis(trihexylsilyloxide) (NIR775), into the matrix of poly (9,9-dioctylfluorene-co-benzothiadiazole) (PFBT) as the Pdot formed using a nanoscale precipitation technique. Free molecules of NIR775 aggregate in aqueous solution, but encapsulating them into the hydrophobic Pdot matrix effectively introduced them into aqueous solution for use in biological studies. Most importantly, the brightness of NIR775 was dramatically enhanced because of the excellent light-harvesting ability of PFBT and the very efficient energy transfer from PFBT to NIR775. We anticipate this bright NIR Pdot will be useful in biological measurements and cellular imaging where strong NIR emission is beneficial.
Spliceosomal peptide P140 for immunotherapy of systemic lupus erythematosus: Results of an early phase II clinical trial (2008)

IPP-201101 was found to be safe and well tolerated by subjects. Three SC doses of IPP-201101 at 200 microg significantly improved the clinical and biologic status of lupus patients.
The Endocannabinoid System in Peripheral Lymphocytes as a Mirror of Neuroinflammatory Diseases (2008)

During immuno-mediated attack of the brain, activation of endocannabinoids represents a protective mechanism, aimed at reducing both neurodegenerative and inflammatory damage through various and partially converging mechanisms that involve neuronal and immune cells. Here, we review the main alterations of the endocannabinoid system (ECS) within the central nervous system and in peripheral blood mononuclear cells, in order to discuss the intriguing observation that elements of the peripheral ECS mirror central dysfunctions of endocannabinoid signaling. As a consequence, elements of blood ECS might serve as novel, non-invasive diagnostic tools of several neurological disorders, and targeting the ECS might be useful for therapeutic purposes. In addition, we discuss the appealing working hypothesis that the presence of type-1 cannabinoid receptors on the luminal side, and that of type-2 cannabinoid receptors on the abluminal side of the blood-brain barrier, could drive a unidirectional transport of AEA in the luminal --> abluminal direction (i.e., from blood to brain), thus implying that blood may be a reservoir of AEA for the brain. On this basis, it can be expected that an unbalance of the endogenous tone of AEA in the blood may sustain a similar unbalance of its level within the brain, as demonstrated in Huntington's disease, Parkinson's disease, multiple sclerosis, attention-deficit/hyperactivity disorder, schizophrenia, depression and headache.
Analytic Reviews: High-Frequency Oscillatory Ventilation (HFOV) and Airway Pressure Release Ventilation (APRV): A Practical Guide (2009)

Despite advances in ventilator management, 31% to 38% of patients with adult respiratory distress syndrome (ARDS) will die, some from progressive respiratory failure. Inability to adequately oxygenate patients with severe ARDS has prompted extensive efforts to identify what are now known as alternative modes of ventilation including high-frequency oscillatory ventilation and airway pressure release ventilation. Both modalities are based on the principles of the open-lung concept and aim to improve oxygenation by keeping the lung uniformly inflated for an extended period of time. Although a mortality benefit has not been proven, some patients may benefit from these alternative modes of ventilation as rescue measures while the underlying process resolves. The purpose of this article is to review the evidence and mechanisms underlying each modality and to describe the fundamental steps in initiating, adjusting, and terminating these modes of ventilation.
Complex Formation between Carboxylic Acids and Divalent Metal Cations (1938)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTComplex Formation between Carboxylic Acids and Divalent Metal CationsR. Keith Cannan and Andre KibrickCite this: J. Am. Chem. Soc. 1938, 60, 10, 2314–2320Publication Date (Print):October 1, 1938Publication History Published online1 May 2002Published inissue 1 October 1938https://pubs.acs.org/doi/10.1021/ja01277a012https://doi.org/10.1021/ja01277a012research-articleACS PublicationsRequest reuse permissionsArticle Views1791Altmetric-Citations204LEARN 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
Cr(VI) Reduction by Sulfidogenic and Nonsulfidogenic Microbial Consortia (2003)

In time course experiments, bacterial community compositions were compared between a sulfidogenic and two nonsulfidogenic Cr(VI)-reducing consortia enriched from metal-contaminated sediments. The consortia were subjected to 0 and 0.85 mM or 1.35 mM Cr(VI), and Cr(VI) reduction, growth, and denaturing gradient gel electrophoresis profiles of PCR products of small-subunit (16S) ribosomal genes were compared. Results showed that although Cr(VI) was completely reduced by the three consortia, Cr(VI) inhibited cell growth, with sulfate-reducing bacteria being particularly sensitive to Cr(VI) toxicity relative to other bacteria in the consortia.
Gemfibrozil for the Secondary Prevention of Coronary Heart Disease in Men with Low Levels of High-Density Lipoprotein Cholesterol (1999)

Gemfibrozil therapy resulted in a significant reduction in the risk of major cardiovascular events in patients with coronary disease whose primary lipid abnormality was a low HDL cholesterol level. The findings suggest that the rate of coronary events is reduced by raising HDL cholesterol levels and lowering levels of triglycerides without lowering LDL cholesterol levels.
Spleen Tyrosine Kinase Is Overexpressed and Represents a Potential Therapeutic Target in Chronic Lymphocytic Leukemia (2009)

B-cell receptor signaling contributes to apoptosis resistance in chronic lymphocytic leukemia (CLL), limiting the efficacy of current therapeutic approaches. In this study, we investigated the expression of spleen tyrosine kinase (SYK), a key component of the B-cell receptor signaling pathway, in CLL and its role in apoptosis. Gene expression profiling identified enhanced expression of SYK and downstream pathways in CLL compared with healthy B cells. Immunoblotting showed increased expression and phosphorylation of SYK, PLCgamma(2), signal transducers and activators of transcription 3, and extracellular signal regulated kinase 1/2 in CLL compared with healthy B cells, suggesting enhanced activation of these mediators in CLL. SYK inhibitors reduced phosphorylation of SYK downstream targets and induced apoptosis in primary CLL cells. With respect to prognostic factors, SYK inhibitors exerted stronger cytotoxic effects in unmutated and ZAP70(+) cases. Cytotoxic effects of SYK inhibitors also associated with SYK protein expression, potentially predicting response to therapy. Combination of fludarabine with SYK Inhibitor II or R406 increased cytotoxicity compared with fludarabine therapy alone. We observed no stroma-contact-mediated drug resistance for SYK inhibitors as described for fludarabine treatment. CD40 ligation further enhanced efficacy of SYK inhibition. Our data provide mechanistic insight into the recently observed therapeutic effects of the SYK inhibitor R406 in CLL. Combination of SYK inhibitors with fludarabine might be a novel treatment option particularly for CLL patients with poor prognosis and should be further evaluated in clinical trials.
PPAR Agonists, Atherogenic Dyslipidemia and Cardiovascular Risk (2016)

Peroxisome proliferator-activated receptors (PPAR) are implicated in the pathology of several metabolic diseases including obesity, diabetes, and atherosclerosis. PPAR agonists exert multiple lipid modifying actions which are beneficial to the prevention of atherosclerosis. Such benefits in lipid lowering actions include improvements in atherogenic dyslipidemia that seems to be particularly expressed in individuals at higher cardiovascular (CV) risk. In addition, the favorable effects of PPAR agonists on different cardio-metabolic parameters are established in several metabolic conditions, such as diabetes mellitus, insulin resistance, and heightened systemic inflammation. The goal of this review is to summarize the current evidence on PPAR agonists and their effects on atherogenic dyslipidemia and CV risk. The main findings indicate that PPAR agonists improve not only the lipid profile, but also lipoprotein subfractions associated with atherogenic dyslipidemia and other CV markers. However, future prospective studies are required to establish the long-term effects of such therapies on atherogenic lipoproteins and their benefit on CV outcomes.
Effect of acute inhibition of nitric oxide synthesis byl‐NAME on cardiovascular responses following peripheral autonomic blockade in rabbits (2006)

The pressor and chronotropic responses to acute inhibition of nitric oxide synthase enzyme by N(G)-nitro-L-arginine methyl ester (L-NAME) were studied in anaesthetized rabbits with intact autonomic nervous system (ANS) activity. Also, they were investigated when administration of L-NAME was preceded by peripheral autonomic blockade. Autonomic blockade had different forms: ganglionic (hexamethonium-induced), post-ganglionic beta-adrenergic blockade (propranolol induced), parasympathetic blockade (atropine induced), and complete autonomic blockade by coadministration of hexamethonium and atropine simultaneously. L-NAME injected intravenously (10 mg/kg) in animals with intact and blocked autonomic activity induced a pressor response. This pressor response was accompanied by bradycardia in rabbits with either intact autonomic activity or hexamethonium-induced ganglionic blockade. L-NAME exerted no effect on heart rate in animals with beta-adrenergic blockade or parasympathetic blockade. In rabbits with complete autonomic blockade, L-NAME evoked tachycardia. These experiments indicate that L-NAME-induced hypertension is not relying only on ANS. Also, L-NAME-induced tachycardia in rabbits treated with atropine plus hexamethonium suggests other humoral mechanisms that may be involved in the L-NAME induced chronotropic response.