gebhart/patrepeval huggingface dataset:
Comparison of the intoxication pathways of tumor necrosis factor and diphtheria toxin (1990)

The mechanism by which tumor necrosis factor alpha (TNF) initiates tumor cell destruction is unknown. Having established that a brief drop in extracellular pH enhances the killing activity of TNF, our next objective was to explore whether TNF-induced cell death is dependent on endosomal acidification. Diphtheria toxin (DTx), a well-characterized acid-dependent cytotoxin, served as an indicator of the effectiveness of each treatment condition. Studies with lysosomotropic agents demonstrated that the cytotoxic pathway of TNF can operate independently of low pH exposure in contrast to the lethal pathway of DTx. When NH4Cl-treated cells were exposed to TNF at low pH, the level of killing increased two- to threefold over that attained with cells maintained at neutral pH (either with or without NH4Cl). Furthermore, inhibition of metabolic processes by sodium azide in combination with 2-deoxyglucose severely reduced DTx killing but stimulated TNF killing. Despite these differences, TNF and DTx provoked extensive internucleosomal DNA cleavage in prelytic target cells. Inhibitor of nuclear poly(ADP-ribose) transferase also evoked similar levels of cellular resistance to both cytotoxins. Models for DTx- and TNF-induced cytolysis are discussed in view of these new discoveries.
Retrovirus-induced immunodeficiency in the mouse (1992)

Morse, Herbert C. III; Chattopadhyay, Sisir K.; Makino, Masahiko; Fredrickson, Torgny N.; Hügin, Ambros W.; Hartley, Janet W. Author Information
Synthetic investigations of rapamycin. 1. Synthesis of a C10-C21 fragment (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthetic investigations of rapamycin. 1. Synthesis of a C10-C21 fragmentStephanie D. Meyer, Tetsuo Miwa, Masashi Nakatsuka, and Stuart L. SchreiberCite this: J. Org. Chem. 1992, 57, 19, 5058–5060Publication Date (Print):September 1, 1992Publication History Published online1 May 2002Published inissue 1 September 1992https://pubs.acs.org/doi/10.1021/jo00045a007https://doi.org/10.1021/jo00045a007research-articleACS PublicationsRequest reuse permissionsArticle Views608Altmetric-Citations33LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Long-acting Growth Hormones Produced by Conjugation with Polyethylene Glycol (1996)

Derivatives of human growth hormone (hGH) of increasing size were produced by reaction with the N-hydroxysuccinimide ester of polyethylene glycol-5000 (PEG5000), a 5-kDa reagent that selectively conjugates to primary amines. By adjusting the reaction conditions and purification procedure, it was possible to isolate hGH derivatives containing up to seven PEG moieties that altered the Stokes radius and thereby the effective molecular masses of the unmodified hormone from 22 to 300 kDa. Fortunately, the most reactive amines were ones that did not lie in either of the two sites important for receptor binding. Nonetheless, increasing the level of PEG modification linearly reduced the affinity of hGH for its receptor and increased the EC50 in a cell-based assay up to 1500-fold. Most of the reduction in affinity was the result of slowing the association rate for the receptor. The clearance rate of hGH in rats was inversely proportional to effective molecular weight and closely fit a filtration model. We have tested the potency of these analogs by injecting them daily or every 6 days into hypophysectomized rats and determining the effects on body and organ growth. The efficacy of these analogs was optimal for hGH conjugated with 5 eq of PEG5000, and the potency was increased by about 10-fold compared with unmodified hGH. Such PEG-hGH derivatives show promise as long-acting alternatives to daily injections of hGH. More generally these studies show that improving hormone clearance properties, even at the expense of reducing receptor binding affinity, can lead to dramatic increases in hormone efficacy.
Self‐Assembly of Coiled Coils in Synthetic Biology: Inspiration and Progress (2010)

Biological self-assembly is very complex and results in highly functional materials. In effect, it takes a bottom-up approach using biomolecular building blocks of precisely defined shape, size, hydrophobicity, and spatial distribution of functionality. Inspired by, and drawing lessons from self-assembly processes in nature, scientists are learning how to control the balance of many small forces to increase the complexity and functionality of self-assembled nanomaterials. The coiled-coil motif, a multipurpose building block commonly found in nature, has great potential in synthetic biology. In this review we examine the roles that the coiled-coil peptide motif plays in self-assembly in nature, and then summarize the advances that this has inspired in the creation of functional units, assemblies, and systems.
Strategies for adapting automated seizure detection algorithms (2006)

The time-varying dynamics of epileptic seizures and the high inter-individual variability make their detection difficult. Osorio et al. [Osorio, I, Frei, MG, Wilkinson, SB. Real-time automated detection and quantitative analysis of seizures and short-term prediction of clinical onset. Epilepsia 1998;39(6):615-27] developed an algorithm that has had success in detecting seizures. We present a new strategy for adapting this algorithm or other algorithms to an individual's seizure fingerprint using both seizure and non-seizure training segments and a novel performance criterion that directly incorporates the non-linearity and lack of differentiability of the algorithm. The joint optimization of a linear filter chosen from a bank of candidate filters and of a percentile used in order statistic filtering provides an empirical solution that is both practical and useful, which should translate into improved sensitivity, specificity and detection speed. This premise is strongly supported by the results obtained in a large validation study and the examples illustrated in this article. This strategy is generalizable to other detection algorithms with modular architecture and spectral filters.
Musical Applications of Electric Field Sensing (1997)

The Theremin was one of the first electronic musical instruments, yet it provides a degree of expressive real-time control that remains lacking in most modern electronic music interfaces. Underlying the deceptively simple capacitance measurement used by it and its descendants are a number of surprisingly interesting current transport mechanisms that can be used to inexpensively , unobtrusively, robustly, and remotely detect the position of people and objects. We review the relevant physics, describe appropriate measurement instrumentation, and discuss applications that began with capturing virtuosic performance gesture on traditional stringed instruments and evolved into the design of new musical interfaces.
Vesicle Targeting: Timed Release and Specificity for Leukocytes in Mice by Subcutaneous Injection (1980)

When unilamellar vesicles were administered subcutaneously in mice, the half-time for the destruction of the vesicles varied from 12 to 600 hours, depending on their composition. The vesicles tested consisted of distearoyl phosphatidylcholine, cholesterol, and certain sugar and amino-sugar derivatives of cholesterol. Vesicle with amino-sugar derivatives showed the greatest longevity and became localized with high specificity in aggregates of polymorphonuclear leukocytes. A substantial delay between the time that the vesicles broke open and the time that labels contained in the vesicles were excreted suggests that the vesicles undergo endocytosis before destruction.
Impact of 16S rRNA Gene Sequence Analysis for Identification of Bacteria on Clinical Microbiology and Infectious Diseases (2004)

The traditional identification of bacteria on the basis of phenotypic characteristics is generally not as accurate as identification based on genotypic methods. Comparison of the bacterial 16S rRNA gene sequence has emerged as a preferred genetic technique. 16S rRNA gene sequence analysis can better identify poorly described, rarely isolated, or phenotypically aberrant strains, can be routinely used for identification of mycobacteria, and can lead to the recognition of novel pathogens and noncultured bacteria. Problems remain in that the sequences in some databases are not accurate, there is no consensus quantitative definition of genus or species based on 16S rRNA gene sequence data, the proliferation of species names based on minimal genetic and phenotypic differences raises communication difficulties, and microheterogeneity in 16S rRNA gene sequence within a species is common. Despite its accuracy, 16S rRNA gene sequence analysis lacks widespread use beyond the large and reference laboratories because of technical and cost considerations. Thus, a future challenge is to translate information from 16S rRNA gene sequencing into convenient biochemical testing schemes, making the accuracy of the genotypic identification available to the smaller and routine clinical microbiology laboratories.
Immunohistochemical characterization of the amyloid deposits and quantitation of pertinent cerebrospinal fluid proteins in hereditary cerebral hemorrhage with amyloidosis. (1987)

Cystatin C, a protein inhibitor of lysosomal cysteine proteinases, was demonstrated by immunohistochemical techniques to be present in the birefringent amyloid deposits of the small arteries in the cerebrum, cerebellum, and leptomeninges of 10 Icelandic individuals with hereditary cerebral hemorrhage with amyloidosis. Specimens from other organs were investigated in one of the patients, and amyloid angiopathy characterized by an immunoreactivity of cystatin C was found in a submandibular lymph node. No immunoreactivity of amyloid fibril protein AA, kappa or lambda immunoglobulin light chain, or prealbumin was observed. Significantly low cerebrospinal fluid concentrations of cystatin C were found in all 9 investigated individuals with hereditary cerebral hemorrhage with amyloidosis. The concentrations of beta 2-microglobulin, albumin, and IgG in the cerebrospinal fluid were within normal limits. Isoelectric focusing showed that cystatin C from the cerebrospinal fluid of 9 patients with hereditary cerebral hemorrhage with amyloidosis had an isoelectric point identical to that of normal individuals. This investigation demonstrates that hereditary cerebral hemorrhage with amyloidosis may be diagnosed by two laboratory methods: immunohistochemical investigation of cystatin C in brain tissue specimens and quantitation of cystatin C in cerebrospinal fluid.
Anti-serum albumin domain antibodies for extending the half-lives of short lived drugs (2008)

We have used phage display to isolate a range of human domain antibodies (dAbs) that bind to mouse, rat and/or human serum albumin (SA) and can be expressed at very high levels in bacterial, yeast or mammalian cell culture. In contrast to non-SA-binding dAbs, which have terminal half-lives of less than 45 min, the half-lives of these 12 kDa 'AlbudAbs' can match the half-life of SA itself. To demonstrate the use of AlbudAbs for extending the half-lives of therapeutic drugs, we created a fusion of the interleukin-1 receptor antagonist (IL-1ra) with an AlbudAb. Soluble IL-1ra is potent inhibitor of IL-1 signalling that is approved for the treatment of rheumatoid arthritis but has a relatively short in vivo half-life. Here we show that although the AlbudAb/IL-1ra fusion has a similar in vitro potency, its in vivo efficacy can be dramatically improved due to its extended serum half-life. AlbudAbs could potentially be used to generate a range of long half-life versions of many different drugs in order to improve their dosing regimen and/or clinical effect.
Delta-thalassemia due to a mutation in an erythroid-specific binding protein sequence 3' to the delta-globin gene (1992)

We have previously described a family of Northern Sardinian descent in which the propositus was affected by thalassemia major resulting from compound heterozygosity for codon 39 nonsense mutation and the beta +IVS II nt 745 mutation and in which all heterozygotes for the beta +IVS II nt 745 mutation had normal hemoglobin (Hb) A2 levels. To define the reasons for normal HbA2 levels in otherwise typical beta-thalassemia heterozygotes, we cloned and sequenced the delta-thalassemia gene in cis to the beta +IVS II nt 745 mutation. The sequence analysis showed a single nucleotide substitution (G----A) at position 69 nts (delta +69) downstream to the polyA addition site. Dot blot analysis with an oligonucleotide probe complementary to the delta +69 mutation detected this mutation in several heterozygotes for the beta +IVS II nt 745 mutation from the proband's family, but failed to show it either in a group of normal individuals of the same origin or in nonrelated heterozygotes for the beta +IVS II nt 745 mutation of the same or different descent from the proband. The delta +69 (G----A) mutation may be responsible for the low delta-globin output from the beta +IVS II nt 745 chromosome or could be a silent polymorphism not affecting the function of the delta-globin gene. The normal G at position 69 is part of a sequence very similar to the core DNA (A/T)GATA(A/G) motif (GATA box) that is a binding site for the GATA-1 protein. Gel-retardation assay has shown that a DNA fragment containing the GATA motif with the G----A at position +69 has increased binding affinity for erythroid-specific DNA binding protein(s) as compared with the wild-type sequence. These findings may suggest that the delta +69 mutation is responsible for the deficient function of the in cis delta-globin gene.
Synthesis and antiinflammatory properties of N-substituted 4,5-dioxopyrrolidine-3-carboxanilides (1976)

The synthesis and physical properties of a series of N-methyl- and N-phenyl-4,5-dioxopyrrolidine-3-carboxanilides are described. Unlike previously reported carboxanilides derived from 1,3(2H,4H)-dioxoisoquinoline and 2-oxobenzofuran, the currently described agents exist solely as the enol tautomers and, as a result, do not display comparable acidic properties. None of the newly reported compounds exhibited activity equal to that of aspirin in the carrageenin-induced rat foot edema assay.
Quantitative determination of blood glucose using enzyme induced chemiluminescence of luminol (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTQuantitative determination of blood glucose using enzyme induced chemiluminescence of luminolDebra T. Bostick and David M. HerculesCite this: Anal. Chem. 1975, 47, 3, 447–452Publication Date (Print):March 1, 1975Publication History Published online1 May 2002Published inissue 1 March 1975https://pubs.acs.org/doi/10.1021/ac60353a039https://doi.org/10.1021/ac60353a039research-articleACS PublicationsRequest reuse permissionsArticle Views1059Altmetric-Citations158LEARN 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
Rubisco Synthesis, Assembly, Mechanism, and Regulation. (1995)

After import into chloroplasts and processing, the mature S-subunits are assembled with plastid-synthesized L-subunits into the Lese Rubisco holoenzyme Although Rubisco L-subunits synthesized
Evaluating short-term pain after steroid injection. (2007)

Steroids are injected into joints for various indications. All steroid preparations relieve pain similarly over the long term. Therefore, decisions about which preparation to use are often arbitrary. We evaluated methylprednisolone acetate and a combination of betamethasone diproprionate and betamethasone sodium phosphate for short-term pain and the predictive value of short-term pain. Eighty-five patients were injected in prospective double-blind randomized fashion. Pain was evaluated by visual analog scale (1 = no pain, 10 = severe pain) at baseline, 3 days, and 3 weeks. No patient had joint pain immediately after injection. Three days after injection, mean (SD) pain levels were 5.1 (2.9) for methylprednisolone and 5.2 (2.6) for betamethasone (P = .97); 3 weeks after injection, they were 4.0 (2.8) and 3.7 (2.5), respectively (P = .57). Short-term pain increased from baseline for both preparations and decreased from 3 days to 3 weeks. Pain at 3 days and 3 weeks was positively correlated. This study does not support a difference in short-term pain between preparations. The significant correlation between short- and long-term pain may justify early decisions regarding treatment, especially in patients with high levels of initial pain.
Cloning and Characterization of a Streptomyces Single Module Type Non-ribosomal Peptide Synthetase Catalyzing a Blue Pigment Synthesis (2007)

In the present study, we cloned a gene, designated bpsA, which encodes a single module type non-ribosomal peptide synthetase (NRPS) from a D-cycloserine (DCS)-producing Streptomyces lavendulae ATCC11924. A putative oxidation domain is significantly integrated into the adenylation domain of the NRPS, and the condensation domain is absent from the module. When S. lividans was transformed with a plasmid carrying bpsA, the transformed cells produced a blue pigment, suggesting that bpsA is responsible for the blue pigment synthesis. However, to produce the blue pigment in Escherichia coli, the existence of the 4'-phosphopantetheinyl transferase (PPTase) gene from Streptomyces was necessary, in addition to bpsA. The chemical structure of the pigment was determined as 5,5'-diamino-4,4'-dihydroxy-3,3'-diazadiphenoquinone-(2,2'), called indigoidine. The bpsA gene product, designated BPSA, was overproduced in an E. coli host-vector system and purified to homogeneity, demonstrating that the recombinant enzyme prefers L-Gln as a substrate. The in vitro experiment using L-Gln also showed that the blue pigment was formed by the purified BPSA only when the enzyme was phosphopantetheinylated by adding a Streptomyces PPTase purified from E. coli cells. Each site-directed mutagenesis experiment of Lys(598), Tyr(601), Ser(603), and Tyr(608), which are seen in the oxidation domain of BPSA, suggests that these residues are essential for the binding of FMN to the protein and the synthesis of the blue pigment.
Mechanism of the Acyl-Carbon Cleavage and Related Reactions Catalyzed by Multifunctional P-450s: Studies on Cytochrome P-45017.alpha. (1994)

It is now well-known that conventional cytochrome P-450s catalyze hydroxylation reactions using an iron mono-oxygen species, the structure of which, as inferred from chemical model studies, may be drrepresented by the following canonical forms: FeV==O<-->(.+)FeIV==O<-->FeIV--O(.). Certain multifunctional P-450s, notably those involved in steroid biosynthesis, catalyze, in addition to hydroxylation reactions, an acyl-carbon cleavage process in which the participation of an iron peroxide intermediate, FeIII--OOH, has been suggested. However the possibility still exists that the C--C bond cleavage may also occur using the FeV==O species. We have scrutinized the chemical consequences of involving either an FeV==O or an FeIII--OOH species for five different C--C bond cleavage reactions. With respect to the status as well as the origin of hydrogen and oxygen atoms, in four of the examples the mechanism involving the FeV==O species makes the same prediction as that using the iron peroxide intermediate, that is, the incorporation of an atom of oxygen from O2 into acyl part of the cleaved fragment. The fifth example, however, involving the formation, with pig testes microsomes, of 17 alpha-hydroxyandrogen (androst-5-ene-3 beta,17 alpha-diol) from pregnenolone, presents an interesting contrast--in this case different outcomes are predicted by the two mechanisms. These possibilities have been experimentally evaluated using substrates stereo- and regiospecifically labeled with heavy isotopes and incubated with pig testes microsomes under either 16O2 or 18O2.(ABSTRACT TRUNCATED AT 250 WORDS)
Antigenic relationships between six genotypes of the small hydrophobic protein gene of mumps virus (2002)

Six different genotypes of mumps virus, A, C, D, G, H and I, genotyped on the basis of the small hydrophobic protein gene sequence, were subjected to antigenic comparison. Monoclonal antibodies directed against the haemagglutinin-neuraminidase protein of the SBL-1 strain of genotype A were used in immunofluorescence tests with different mumps virus strains. In addition, the six virus genotypes were compared by cross-neutralization tests with human post-vaccination sera after vaccination with the Jeryl Lynn (JL) strain of mumps virus and with rabbit hyperimmune sera directed against the A or D genotypes of mumps virus. Genotypes C, D, G, H and I could not be antigenically separated. In contrast, three different virus strains of genotype A, SBL-1, JL and Kilham, were distinct and were found to represent three different serotypes within the A genotype of mumps virus. Vaccination of Swedish children with the JL strain of mumps virus resulted in clearly lower neutralization titres against the SBL-1 strain, which is endemic in Sweden, compared to the homologous vaccine titres.