gebhart/patrepeval huggingface dataset:
Structural and functional characterization of human immunodeficiency virus tat protein (1989)

Site-directed mutagenesis was used to identify functional domains present within the human immunodeficiency virus (HIV) tat protein. Transient cotransfection experiments showed that derivatives of tat protein with amino acid substitutions either at the amino-terminal end or at cysteine residue 22, 37, 27, or 25 were no longer able to transactivate HIV long terminal repeat-directed gene expression. Incubation of Tat expressed in Escherichia coli with zinc demonstrated that both authentic Tat and cysteine mutation derivatives could form metal-protein complexes. The tat proteins that contained alterations within the cluster of positively charged amino acid residues retained their ability to transactivate gene expression, albeit at markedly reduced levels. Indirect immunofluorescence showed that the authentic tat protein and the amino-terminal and cysteine substitution mutants all localized in the nucleus, with accumulation being most evident in the nucleolus. In contrast, nuclear accumulation was greatly reduced with the basic-substitution mutations. Consistent with this result, a fusion protein that contained amino acids GRKKR, derived from the basic region, fused to the amino-terminal end of beta-galactosidase also accumulated within the nucleus. These results demonstrate that the 14-kilodalton tat protein contains at least three distinct functional domains affecting localization and transactivation.
Reconstitution of Escherichia coli 30 S Ribosomal Subunits from Purified Molecular Components (1973)

Abstract Reconstitution of 30 S ribosomal subunits from 16 S RNA and a mixture of purified individual 30 S ribosomal proteins has been studied. Proteins from the 30 S ribosomal subunit of Escherichia coli were purified by a combination of phosphocellulose and DEAE-chromatography, and Sephadex gel filtration. The proteins purified correspond to the 21 proteins generally accepted as 30 S proteins, with the exception of two proteins, P3b and P3c, which correspond to the protein S6 studied by other workers. P3b and P3c are closely related, and one is probably a derivative of the other. Using a mixture of these purified proteins, reconstitution of functionally active 30 S subunits has been demonstrated. Reconstituted particles had higher activities in poly(U)-directed polyphenylalanine synthesis than reference 30 S particles in several experiments. The functional activity of reconstituted particles was also examined in several other assays; these included natural messenger RNA-directed polypeptide synthesis, poly(U)-directed Phe-tRNA binding, AUG-directed fMet-puromycin formation, AUG-directed fMet-tRNA binding, and the binding of termination codon UAA in the presence of chain termination factors. In all cases, activities comparable to reference 30 S subunits were observed. The sedimentation properties and the protein composition of reconstituted particles were also similar to 30 S ribosomal subunits. The kinetics of reconstitution using purified protein mixtures was essentially identical with those of reconstitution using unfractionated 30 S proteins. These results strongly suggest that 21 purified 30 S proteins together with 16 S RNA are sufficient to reconstitute 30 S subunits, and that no essential 30 S components were lost during the fractionation and purification of the 30 S proteins. Single component omission experiments indicated that all purified proteins, except P1(S1) and P3b,c(S6), are required for full functional activity. A requirement for P9a(S16) has been shown in some, but not all, experiments. P3b,c(S6) and P9a(S16) have been shown to be involved in the reconstitution reaction in other experiments (Mizushima, S., and Nomura, M. (1970) Nature 226, 1214; Nomura, M. (1973) Science 179, 864) and therefore are 30 S components. It is still not clear whether P1(S1) should be considered a true 30 S protein or a ribosomal-associated factor.
Functionally distinct agretopic and epitopic sites. Analysis of the dominant T cell determinant of moth and pigeon cytochromes c with the use of synthetic peptide antigens. (1987)

The dominant T cell determinant on moth and pigeon cytochromes c in B10.A (E beta k:E alpha k) mice is located in the C-terminal portion of the protein, contained within residues 93-103 or 93-104. Thirty-seven antigen analogs, containing single amino acid substitutions at positions 98, 99, 101, 102, 103, and 104, were synthesized. The effects of the substitutions on in vitro antigenicity and in vivo immunogenicity were determined. Functional assays with T cell clones identified residues 99, 101, 102, and 103 as critical, based on their effect on antigenic potency. Peptides containing substitutions at residues 99, 101, and 102 were capable of eliciting unique clones upon immunization of B10.A mice. This was consistent with the identification of these residues as part of the epitope, the site on the antigen that interacts with the T cell receptor. Immunization with peptides substituted at residue 103, however, failed to elicit clones with unique specificity for the immunogen. When these peptides were tested for their ability to stimulate the T cell clones with antigen-presenting cells from B10.A(5R) mice expressing the E beta b:E alpha k Ia molecule, a consistent change in the relative antigenic potency was observed with 50% of the peptides. The effect of the Ia molecule on the antigenic potency ruled out the possibility that residue 103 nonspecifically affected antigen uptake or processing and identified residue 103 as part of the agretope, the site that interacts with the Ia molecule. The locations of the agretope and the epitope on this antigenic determinant appear to be fixed, even in the presence of large numbers of amino acid substitutions. However, some substitutions were found to affect both the agretope and the epitope, placing limits on the functional independence of the two sites. The results are discussed in terms of the trimolecular complex model of T cell activation and the implications of these data for antigen-Ia molecule interactions.
Electrical conduction and dielectric breakdown in aluminum oxide insulators on silicon (2000)

Leakage currents and dielectric breakdown were studied in MIS capacitors of metal-aluminum oxide-silicon. The aluminum oxide was produced by thermally oxidizing AlN at 800-1160/spl deg/C under dry O/sub 2/ conditions. The AlN films were deposited by RF magnetron sputtering on p-type Si (100) substrates. Thermal oxidation produced Al/sub 2/O/sub 3/ with a thickness and structure that depended on the process time and temperature. The MIS capacitors exhibited the charge regimes of accumulation, depletion, and inversion on the Si semiconductor surface. The best electrical properties were obtained when all of the AlN was fully oxidized to Al/sub 2/O/sub 3/ with no residual AlN. The MIS flatband voltage was near 0 V, the net oxide trapped charge density, Q/sub 0x/, was less than 10/sup 11/ cm/sup -2/, and the interface trap density, D/sub it/, was less than 10/sup 11/ cm/sup -2/ eV/sup -1/, At an oxide electric field of 0.3 MV/cm, the leakage current density was less than 10/sup -7/ A cm/sup -2/, with a resistivity greater than 10/sup 12/ /spl Omega/-cm. The critical field for dielectric breakdown ranged from 4 to 5 MV/cm. The temperature dependence of the current versus electric field indicated that the conduction mechanism was Frenkel-Poole emission, which has the property that higher temperatures reduce the current. This may be important for the reliability of circuits operating under extreme conditions. The dielectric constant ranged from 3 to 9. The excellent electronic quality of aluminum oxide may be attractive for field effect transistor applications.
Design, Synthesis, and Characterization of a Potent, Nonpeptide, Cell-Permeable, Bivalent Smac Mimetic That Concurrently Targets Both the BIR2 and BIR3 Domains in XIAP (2007)

XIAP is a central apoptosis regulator that inhibits apoptosis by binding to and inhibiting the effectors caspase-3/-7 and an initiator caspase-9 through its BIR2 and BIR3 domains, respectively. Smac protein in its dimeric form effectively antagonizes XIAP by concurrently targeting both its BIR2 and BIR3 domains. We report the design, synthesis, and characterization of a nonpeptide, cell-permeable, bivalent small-molecule (SM-164) which mimics Smac protein for targeting XIAP. Our study shows that SM-164 binds to XIAP containing both BIR domains with an IC50 value of 1.39 nM, being 300 and 7000 times more potent than its monovalent counterparts and the natural Smac AVPI peptide, respectively. SM-164 concurrently interacts with both BIR domains in XIAP and functions as an ultrapotent antagonist of XIAP in both cell-free functional and cell-based assays. SM-164 targets cellular XIAP and effectively induces apoptosis at concentrations as low as 1 nM in the HL-60 leukemia cell line. The potency of bivalent SM-164 in binding, functional, and cellular assays is 2-3 orders of magnitude higher than its corresponding monovalent Smac mimetics.
Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration (2012)

Data visualization is an essential component of genomic data analysis. However, the size and diversity of the data sets produced by today's sequencing and array-based profiling methods present major challenges to visualization tools. The Integrative Genomics Viewer (IGV) is a high-performance viewer that efficiently handles large heterogeneous data sets, while providing a smooth and intuitive user experience at all levels of genome resolution. A key characteristic of IGV is its focus on the integrative nature of genomic studies, with support for both array-based and next-generation sequencing data, and the integration of clinical and phenotypic data. Although IGV is often used to view genomic data from public sources, its primary emphasis is to support researchers who wish to visualize and explore their own data sets or those from colleagues. To that end, IGV supports flexible loading of local and remote data sets, and is optimized to provide high-performance data visualization and exploration on standard desktop systems. IGV is freely available for download from http://www.broadinstitute.org/igv, under a GNU LGPL open-source license.
Telomere length is reset during early mammalian embryogenesis (2004)

The enzyme telomerase is active in germ cells and early embryonic development and is crucial for the maintenance of telomere length. Whereas the different length of telomeres in germ cells and somatic cells is well documented, information on telomere length regulation during embryogenesis is lacking. In this study, we demonstrate a telomere elongation program at the transition from morula to blastocyst in mice and cattle that establishes a specific telomere length set point during embryogenesis. We show that this process restores telomeres in cloned embryos derived from fibroblasts, regardless of the telomere length of donor nuclei, and that telomere elongation at this stage of embryogenesis is telomerase-dependent because it is abrogated in telomerase-deficient mice. These data demonstrate that early mammalian embryos have a telomerase-dependent genetic program that elongates telomeres to a defined length, possibly required to ensure sufficient telomere reserves for species integrity.
Hierarchical characterization of analog integrated CMOS circuits (1998)

This paper presents a new method for hierarchical characterization of analog integrated circuits. For each circuit class, a fundamental set of performances is defined and extracted topology independently. A circuit being characterized is decomposed in general subcircuits. Sizing rules of these topology independent subcircuits are included into the characterization by functional constraints. In this way, bad circuit sizing is detected and located.
A URA3‐Promoter Deletion in a pYES Vector Increases the Expression Level of a Fungal Lipase in Saccharomyces cerevisiae (1996)

A simple deletion of the URA3 promoter from a Saccharomyces cerevisiae expression plasmid was performed. The promoter-deleted plasmid is shown to have an increased expression level of a fungal lipase gene. The deletion probably causes a poor expression of the URA3 selection marker, probably resulting in a higher copy number per cell of the plasmid. This higher copy number can increase the transcript level per cell and there by the expression level. In the case of the fungal lipase gene, the expression level with defined inoculum is increased at least three times. The principle is most likely similar to the LEU2d plasmids described previously. A part of the 2-micron origin of the pYES type plasmid was also deleted by the URA3 promoter deletion without affecting transformation frequency. The URA3 promoter can easily be deleted from most pYES type plasmids by the described method.
Yeast-derived Recombinant DG42 Protein of Xenopus Can Synthesize Hyaluronan in Vitro (1996)

We demonstrate in this report that the Xenopus DG42 gene product made in the yeast Saccharomyces cerevisiae can synthesize authentic high molecular weight hyaluronan (hyaluronic acid; HA) in vitro. Saccharomyces are eukaryotes that do not naturally produce HA or any other molecules known to contain glucuronic acid. Therefore bakers' yeast is a good model system to determine the enzymatic activity of the DG42 protein, which is the topic of recent debate. Membrane extracts prepared from cells expressing DG42 encoded on a plasmid incorporated [14C]glucuronic acid and N-[3H]acetylglucosamine from exogenously supplied UDP-sugar nucleotides into a high molecular mass (10(6) to 10(7) Da) polymer in the presence of magnesium ions. Both sugar precursors were simultaneously required for elongation. Control extracts prepared from cells with the vector plasmid alone or the DG42 cDNA in the antisense orientation did not display this activity. The double-labeled polysaccharide product synthesized in vitro was deemed to be HA by enzymatic analyses; specific HA lyase could degrade the polymer, but it was unaffected by protease or chitinase treatments. The fragments generated by HA lyase were identical to fragments derived from authentic vertebrate HA as compared by high performance liquid chromatography. We conclude that DG42 is a membrane-associated HA synthase capable of transferring both glucuronic acid and N-acetylglucosamine groups.
In vitro neutralizing capacity of commercially available antacid mixtures, and their role in the treatment of peptic ulcer. (1980)

An in vitro technique has been used to determine the neutralizing capacity of liquid antacids. Many locally available preparations have been tested, and the results indicate that they vary strikingly in both neutralizing capacity and cost. This study re-emphasizes the place of antacids in peptic ulcer therapy.
The perception of shading and reflectance (1996)

The luminance of a surface results from the combined effect of its reflectance (albedo) and its conditions of illumination. Luminance can be directly observed, but reflectance and illumination can only be derived by perceptual processes. Human observers are good at judging an object's reflectance in spite of large changes in illumination; this skill is known as "lightness constancy".
Synthesis of 7,9-didecarboxymethoxatin (4,5-dihydro-4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2-carboxylic acid) and comparison of its chemical properties with those of methoxatin and analogous o-quinones. Model studies directed toward the action of PQQ requiring bacterial oxidoreductases and mammalian plasma amine oxidase (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of 7,9-didecarboxymethoxatin (4,5-dihydro-4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2-carboxylic acid) and comparison of its chemical properties with those of methoxatin and analogous o-quinones. Model studies directed toward the action of PQQ requiring bacterial oxidoreductases and mammalian plasma amine oxidasePaul R. Sleath, J. Barry Noar, Gert A. Eberlein, and Thomas C. BruiceCite this: J. Am. Chem. Soc. 1985, 107, 11, 3328–3338Publication Date (Print):May 1, 1985Publication History Published online1 May 2002Published inissue 1 May 1985https://pubs.acs.org/doi/10.1021/ja00297a044https://doi.org/10.1021/ja00297a044research-articleACS PublicationsRequest reuse permissionsArticle Views1089Altmetric-Citations74LEARN 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
Small-particle research: physicochemical properties of extremely small colloidal metal and semiconductor particles (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSmall-particle research: physicochemical properties of extremely small colloidal metal and semiconductor particlesArnim HengleinCite this: Chem. Rev. 1989, 89, 8, 1861–1873Publication Date (Print):December 1, 1989Publication History Published online1 May 2002Published inissue 1 December 1989https://pubs.acs.org/doi/10.1021/cr00098a010https://doi.org/10.1021/cr00098a010research-articleACS PublicationsRequest reuse permissionsArticle Views8795Altmetric-Citations2552LEARN 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
Thalidomide alone or in combination with fludarbabine are effective treatments for patients with fludarabine-relapsed and refractory CLL (2005)

6640 Background: CLL is characterized by an accumulation of lymphocytes due to a defect in apoptosis. CLL lymphocytes demonstrate increased NF-κB activity which may play a role in mediating resistance to fludarabine. Additionally, several cytokines have been linked to enhanced CLL survival, including TNF-α, bFGF, and VEGF. Given thalidomide’s ability to inhibit these cytokines and NF-κB activity, we investigated whether thalidomide alone or in combination with fludarabine is an effective treatment in CLL. Methods: Patients with CLL who were previously treated with fludarabine were randomized to receive either thalidomide alone (T) or in combination with fludarabine (FT). Thalidomide was started at a dose of 200 mg each night and adjusted as tolerated. Patients assigned to combination therapy started thalidomide prior to receiving fludarabine at a dose of 25 mg/m2/d x 5 days, every four weeks for a total of six cycles. Results: 16 pts have been enrolled, including 6 pts refractory to fludarabine, and randomized to receive either T (n=8) or FT (n=8). The median dose of thalidomide was 200 mg qHS (range 50–450). Of the 10 evaluable patients, there have been 1 CR (FT), 4 PRs (1T/3FT), 2 hematologic improvements (1T/1FT), 2 minor responses (1T/1FT), and one disease progression (T). Therapy was tolerated, with grade 3 toxicities being: neuropathy(2), sedation(1), thrombosis(1), febrile neutropenia(1), and infection(3). Of interest, 5 pts on T developed tumor flares, characterized by fevers, increased size and tenderness of lymph nodes, increased lymphocyte counts, and decreased hemoglobin and platelet counts. These symptoms resolved with either continued treatment (3 pts) or temporarily discontinuing the thalidomide(2 pts). Patients receiving thalidomide alone demonstrated hematologic improvement prior to achieving significant decreases in lymph node size. Conclusions: Thalidomide demonstrates activity alone and in combination with fludarabine as treatment for CLL. The combination appears to be particularly effective as treatment for patients refractory to fludarabine. The addition of F to T appears to ameliorate the development of a tumor flare. No significant financial relationships to disclose.
Myostatin expression in ventricular myocardium in a rat model of volume‐overload heart failure (2006)

Myocardial myostatin mRNA and protein expression were up-regulated in the rat model of volume-overload heart failure. Treatment with carvedilol is associated with a limitation of increased myostatin expression in the failing ventricular myocardium.
Plasma N-terminal pro-brain natriuretic peptide and the ECG in the assessment of left-ventricular systolic dysfunction in a high risk population (1999)

Of the variables studies, N-terminal pro-brain natriuretic peptide had the strongest correlation with reduced left ventricular wall motion index. The electrocardiogram had a poor predictive value for left ventricular systolic dysfunction in this population. Plasma N-terminal pro-brain natriuretic peptide can usefully predict patients with a reduced left ventricular wall motion index in whom echocardiographic examination may be appropriate.
Long-term episomal gene delivery in human lymphoid cells using human and avian adenoviral-assisted transfection. (1994)

Human B-lymphoblastoid cells transformed by Epstein-Barr virus (EBV), a common source of established human cell lines, are generally refractory to standard DNA transfection methods. We report here the use of human and chicken adenoviruses for the stable delivery of plasmid DNA carrying the latent origin of replication, oriP, from EBV into human B-lymphoblastoid cells. Long-term hygromycin-resistant transformants of human lymphoblastoid cells belonging to the genetically unstable inherited disease Fanconi's anemia were obtained by adenoviral-assisted transfection of plasmid DNA complexed to either human adenovirus type 5 (Ad5) or avian adenovirus type 1 (CELO). Successful long-term transformation of human lymphoblastoid cells was unrelated to the efficiency of short-term transfection as measured by the transient expression level of a reporter lacZ gene. The human or avian adenoviral binary conjugates, with no other cell ligand, were sufficient for stable cell transformation. The amount of DNA established in the human B-cell transformants was approximately 100-fold higher with the CELO virus. We conclude that Ad5-assisted transfection is more suitable for transient gene expression studies in human lymphoblastoid cells, while CELO-assisted transfection appears the method of choice for stable genetic transformation of such cells. Such differential short- and long-term gene delivery strategy with Ad5 and CELO may be useful in gene therapy of human B cells involving cancers and inherited diseases, respectively.