gebhart/patrepeval huggingface dataset:
Pharmacokinetics, biodistribution and cell uptake of antisense oligonucleotides (2015)

Pharmacokinetic properties of oligonucleotides are largely driven by chemistry of the backbone and thus are sequence independent within a chemical class. Tissue bioavailability (% of administered dose) is assisted by plasma protein binding that limits glomerular filtration and ultimate urinary excretion of oligonucleotides. The substitution of one non-bridging oxygen with the more hydrophobic sulfur atom (phosphorothioate) increases both plasma stability and plasma protein binding and thus, ultimately, tissue bioavailability. Additional modifications of the sugar at the 2' position, increase RNA binding affinity and significantly increase potency, tissue half-life and prolong RNA inhibitory activity. Oligonucleotides modified in this manner consistently exhibit the highest tissue bioavailability (>90%). Systemic biodistribution is broad, and organs typically with highest concentrations are liver and kidney followed by bone marrow, adipocytes, and lymph nodes. Cell uptake is predominantly mediated by endocytosis. Both size and charge for most oligonucleotides prevents distribution across the blood brain barrier. However, modified single-strand oligonucleotides administered by intrathecal injection into the CSF distribute broadly in the CNS. The majority of intracellular oligonucleotide distribution following systemic or local administration occurs rapidly in just a few hours following administration and is facilitated by rapid endocytotic uptake mechanisms. Further understanding of the intracellular trafficking of oligonucleotides may provide further enhancements in design and ultimate potency of antisense oligonucleotides in the future.
The Structural Proteins of Chick Embryo Lethal Orphan Virus (Fowl Adenovirus Type 1) (1984)

Chick embryo lethal orphan (CELO) virus (fowl adenovirus type 1) contains at least 14 structural proteins with polypeptide molecular weights ranging from 100K to about 6K. A nomenclature of the CELO virion polypeptides is presented and the molar proportion of each polypeptide has been estimated. The CELO virus pentons were specifically released from the virion by dialysis against borate-based calcium-magnesium saline. The penton base (polypeptide III, mol. wt. 92K) and two fibres were separated, characterized and their polypeptides were correlated with their morphological positions in the virion. Peptide mapping suggested that the long fibre (polypeptide IV, mol. wt. 65K), and the short fibre (polypeptide VII, mol. wt. 44.5K) were not related in their primary sequences and are therefore probably encoded by separate genes. The time course of synthesis of the CELO virion polypeptides indicated that, like their mammalian adenovirus counterparts, they are synthesized late (after viral DNA replication).
Visual Arts on the Edge: Marginality and Regeneration (2003)

North East Scotland is on the edge between the urban central belt of Scotland and the North Sea.This outcrop of land edged by water -the North Sea, has a rich vernacular cultural heritage that predates the more dominant culture of Scotland's densely populated 'Central Belt', which includes the cities of Edinburgh and Glasgow with their industrial and post -industrial characters.Within rural areas of Northern Scotland industries such as fishing and agriculture manifest change in a different way from urban centres.Processes of change are slower, less visible, cutting deeper into longer term memory and identities structured around a 'sense of place'.The opportunities for regeneration are fewer than in a city as a consequence of the less diverse economic and social infrastructure.It would be inappropriate to think of the arts as a tool of regeneration in these contexts in the same way as has occurred in urban post -industrial contexts.Artistic expression in remote rural areas is challenged by a different experience of the past and present, and therefore a different sense of the future.
Lanthanide Complexes in Multifunctional Asymmetric Catalysis (2002)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLanthanide Complexes in Multifunctional Asymmetric CatalysisMasakatsu Shibasaki and Naoki YoshikawaView Author Information Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan Cite this: Chem. Rev. 2002, 102, 6, 2187–2210Publication Date (Web):May 24, 2002Publication History Received23 October 2001Published online24 May 2002Published inissue 1 June 2002https://pubs.acs.org/doi/10.1021/cr010297zhttps://doi.org/10.1021/cr010297zresearch-articleACS PublicationsCopyright © 2002 American Chemical SocietyRequest reuse permissionsArticle Views10005Altmetric-Citations1123LEARN 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 SUBJECTS:Aldehydes,Aldol reactions,Catalysts,Ketones,Lanthanides Get e-Alerts
An Effective Method of Intraneural Inoculation of Poliomyelitis Virus. (1940)

The uncertainty of results obtained by most investigators with intraneural injections of poliomyelitis virus has limited the use of this method of inoculation for inducing experimental poliomyelitis. Neveretheless, if the virus of poliomyelitis is truly neurotropic, one would expect that intraneural inoculation would be as effective as intracerebral inoculation, and simpler, if the virus could actually be made to come into contact with numerous nerve fibers, rather than being forced along and between connective tissue sheaths within the peripheral nerve. This of course is strongly suggested by the work of Fairbrother and Hurst, who showed that trauma during intraneural injection facilitates “takes” by this method of inoculation. Going one step farther, and with the knowledge that during the first few days after nerve section the nerve cells with axons cut are more susceptible to the virus than normal cells, it was decided to determine whether simple section of a peripheral nerve and immersion of the central stump in virus suspension for a few minutes was sufficient to produce poliomyelitis. This method, which involves no mechanical injection pressure, and which places the virus in contact with the protoplasm of every axon in the nerve, was found to be highly successful in producing poliomyelitis. When a large nerve, such as the sciatic nerve, was used, this method of inoculation was invariably successful with two strains of known potency, the MV and Wfd strains. In 9 Rhesus monkeys the sciatic nerve was sectioned with sharp scissors peripheral to the sciatic notch or at the mid-thigh level, and the central cut end then soaked in as little as 0.1 cc of 20% virus suspension for several minutes. Poliomyelitis resulted after an incubation period of 4-6 days.
Localization of Glial Cell Line‐derived Neurotrophic Factor (GDNF) mRNA in Embryonic Rat by In Situ Hybridization (1996)

The localization of glial cell line-derived neurotrophic factor (GDNF) mRNA was studied by in situ hybridization in rat from embryonic (E) day E10 to E15. At E10, GDNF mRNA is found in the urogenital field and the cranial part of the gut. At E11, the most abundant expression of GDNF mRNA is seen in the epithelial cells of the second, third and fourth pharyngeal pouches, the third and fourth pharyngeal arches and pharynx. Also mesenchymal cells of the gut and mesonephric tubules contain GDNF mRNA. At E13, expression is observed in the mesenchymal cell layers of the oesophagus, intestine and stomach, the mesenchymal cells around the condensing cartilages and metanephric kidney mesenchyme. Also, the epithelia of Rathke's pouch and pharynx are intensely labelled. High expression of GDNF mRNA continues at E15 in kidney, gastrointestinal tract and cartilage. At that stage, GDNF mRNA is seen also in whisker pad and skeletal muscles. The distribution of GDNF mRNA in embryonic rat suggests important roles for GDNF in the early differentiation of the kidney tubules, the innervation of the gastrointestinal tract and the differentiation process of the cartilage and muscle. Our results indicate novel functions for GDNF outside the nervous system.
Saxitoxin, a toxic marine natural product that targets a multitude of receptors (2006)

Covering: up to the end of 2005
Heterodimers of Placenta Growth Factor/Vascular Endothelial Growth Factor (1996)

Here we show that the Escherichia coli expressed monomers of placenta growth factor (PLGF)129 and vascular endothelial growth factor (VEGF)165 can be re-folded in vitro to form PLGF/VEGF heterodimers. The purified recombinant PLGF/VEGF heterodimers and VEGF homodimers have potent mitogenic and chemotactic effects on endothelial cells. However, PLGF/VEGF heterodimers display 20-50-fold less mitogenic activity than VEGF165 homodimers. In contrast, PLGF129 homodimers have little or no effect in these in vitro assays. We also demonstrate the presence of natural PLGF/VEGF heterodimers in the conditioned media of various human tumor cell lines. While PLGF/VEGF heterodimers bind with high affinity to a soluble Flk-1/KDR receptor, PLGF129 homodimers fail to bind to this receptor. Cross-linking of 125I-ligands to human umbilical vein endothelial cells reveals that PLGF/VEGF heterodimers and VEGF165 homodimers, but not PLGF129 homodimers, form complexes with membrane receptors. VEGF165 homodimers and PLGF/VEGF heterodimers stimulate tyrosine phosphorylation of a 220-kDa protein, the expected size for the KDR receptor in human umbilical vein endothelial cells, whereas PLGF129 homodimers are unable to induce tyrosine phosphorylation of this protein. These data indicate that PLGF may modulate VEGF-induced angiogenesis by the formation of PLGF/VEGF heterodimers in cells producing both factors.
Aerobic exercise training for adults with fibromyalgia (2017)

When compared with control, moderate-quality evidence indicates that aerobic exercise probably improves HRQL and all-cause withdrawal, and low-quality evidence suggests that aerobic exercise may slightly decrease pain intensity, may slightly improve physical function, and may lead to little difference in fatigue and stiffness. Three of the reported outcomes reached clinical significance (HRQL, physical function, and pain). Long-term effects of aerobic exercise may include little or no difference in pain, physical function, and all-cause withdrawal, and we are uncertain about long-term effects on remaining outcomes. We downgraded the evidence owing to the small number of included trials and participants across trials, and because of issues related to unclear and high risks of bias (performance, selection, and detection biases). Aerobic exercise appears to be well tolerated (similar withdrawal rates across groups), although evidence on adverse events is scarce, so we are uncertain about its safety.
Nonuniform fast fourier transforms using min-max interpolation (2003)

The fast Fourier transform (FFT) is used widely in signal processing for efficient computation of the FT of finite-length signals over a set of uniformly spaced frequency locations. However, in many applications, one requires nonuniform sampling in the frequency domain, i.e., a nonuniform FT. Several papers have described fast approximations for the nonuniform FT based on interpolating an oversampled FFT. This paper presents an interpolation method for the nonuniform FT that is optimal in the min-max sense of minimizing the worst-case approximation error over all signals of unit norm. The proposed method easily generalizes to multidimensional signals. Numerical results show that the min-max approach provides substantially lower approximation errors than conventional interpolation methods. The min-max criterion is also useful for optimizing the parameters of interpolation kernels such as the Kaiser-Bessel function.
Control of adenovirus acute respiratory disease in U.S. Army trainees. (1975)

Although limited almost exclusively to military trainees, acute respiratory disease (ARD) caused by adenovirus types 4 and 7 had been the leading cause of hospitalization in U.S. Army personnel. This decrease which resembles influenza in clinical manifestations led to hospitalization of as many as 50% of military trainees in midwinter and imposed a heavy burden on military hospitals and training programs. In studies undertaken from 1965 to 1970, live adenovirus type 4 and subsequently type 7 vaccines were found to be safe and immunogenic and to confer protection against type specific adenovirus ARD. For the past 5 yr. military trainees have been immunized with both adenovirus vaccines during periods of expected adenovirus disease. Since 1966, use of adenovirus vaccines has been monitored through the adenovirus surveillance program which yields weekly data on incidence and etiology of ARD in basic combat trainees. Since 1973, stable adenovirus vaccines have resulted in excellent control of adenovirus ARD. Potential problems with this immunization program are discussed.
Hexahistidine (His6)-tag dependent protein dimerization: a cautionary tale. (1999)

Nickel nitrilotriacetic acid (Ni2+-NTA) immobilization of hexahistidine (His6) tagged proteins has become one of the most commonly used methods of affinity chromatography. Perhaps the greatest utility of this protein purification method stems from the general belief that His-tagged proteins (comprised of His6) are little affected in their activities or efficiencies, while alterations in specificity are unexpected. Although this is certainly true in many instances, we present a case in which the biochemical properties of proteins being studied were fundamentally altered due to the presence of His-tags. We carried out these studies using variants of the pi(30.5) protein of plasmid R6K, a DNA binding protein which negatively regulates plasmid replication. Pi(30.5) can bind DNA containing a target sequence (TGAGR) arranged either asymmetrically (direct repeats) in the gamma origin, or symmetrically in inverted half-repeats (IR's) in the operator of its own gene, pir. Importantly, dimers of pi protein bind to an IR; this property allows researchers to quickly assess whether different regulatory variants of pi proteins exhibit altered dimerization properties. For example, pi(30.5) containing a single amino-acid substitution, F107S (pi200(30.5)), has been shown to be monomeric in solution and dimers were not observed bound to IR's. Here we demonstrate that the presence of a His-tag partially restores the ability of pi200(30.5) to dimerize in solution and bind to an IR in dimeric form. This report sends an important message that (other) proteins containing His-tags may differ from their wild type counterparts in dimerization/oligomerization properties.
Exercise assessment of transgenic models of human cardiovascular disease (2003)

Exercise provides one of the most severe, yet physiological, stresses to the intact cardiovascular system and is a major determinant of the utilization of metabolic substrates. The adaptations to exercise are the result of a coordinated response of multiple organ systems, including cardiovascular, pulmonary, endocrine-metabolic, immunologic, and skeletal muscle. With the proliferation of genetically altered murine models of cardiovascular disease, the importance of developing methods of accurate physiological phenotyping is critical. There are numerous examples of transgenic models in which the baseline cardiovascular phenotype is unchanged or minimally changed from the wild type, only to become manifest during the stress of exercise testing. In this review, we cover the basics of the murine cardiovascular response to exercise and the importance of attending to strain differences, compare different exercise methodologies (constant workload treadmill, incremental workload treadmill, swimming) and hemodynamic monitoring systems, and examine the murine response to exercise conditioning. Several examples where exercise studies have contributed to the elucidation of cardiovascular phenotypes are reviewed: the beta-adrenergic receptor knockouts, phospholamban knockout, dystrophin knockout (mdx), and the mutant alpha-myosin heavy chain (R403Q) transgenic.
Regulation of coenzyme A biosynthesis (1981)

Coenzyme A (CoA) and acyl carrier protein are two cofactors in fatty acid metabolism, and both possess a 4'-phosphopantetheine moiety that is metabolically derived from the vitamin pantothenate. We studied the regulation of the metabolic pathway that gives rise to these two cofactors in an Escherichia coli beta-alanine auxotroph, strain SJ16. Identification and quantitation of the intracellular and extracellular beta-alanine-derived metabolites from cells grown on increasing beta-alanine concentrations were performed. The intracellular content of acyl carrier protein was relatively insensitive to beta-alanine input, whereas the CoA content increased as a function of external beta-alanine concentration, reaching a maximum at 8 microM beta-alanine. Further increase in the beta-alanine concentration led to the excretion of pantothenate into the medium. Comparing the amount of pantothenate found outside the cell to the level of intracellular metabolites demonstrates that E. coli is capable of producing 15-fold more pantoic acid than is required to maintain the intracellular CoA content. Therefore, the supply of pantoic acid is not a limiting factor in CoA biosynthesis. Wild-type cells also excreted pantothenate into the medium, showing that the beta-alanine supply is also not rate limiting in CoA biogenesis. Taken together, the results point to pantothenate kinase as the primary enzymatic step that regulates the CoA content of E. coli.
Concentration of Lactoferrin in Milk of Normal Lactating Cows and Changes Occurring During Mastitis (1975)

The mean lactoferrin (Lf) concentration determined by electroimmunodiffusion (EID) assay of whey preparations from 80 quarters of 20 normal lactating cows was 0.35 mg/ml. The mean alpha-lactalbumin (alpha-LAC) and bovine serum albumin (BSA) concentrations were 2.01 mg/ml and 0.29 mg/ml, respectively. The mean was significantly related to cell count (P smaller than 0.01), BSA (P smaller than 0.05), stage of lactation (P smaller than 0.05), and milk production (P smaller than 0.05). The Lf-milk production relationship was the only negative correlation. In 11 cows with mastitis, there was a significant (P smaller than 0.01) increase in mean Lf concentration in infected quarters from 0.55 mg/ml on day 1 of the infection to 1.89 mg/ml by day 3. By day 15 clinical signs had subsided and mean Lf concentrations had decreased to near day 1 values. On day 3 quarters infected with coliform bacteria (clinical mastitis generally more severe) had mean Lf values more than twofold greater than those quarters infected with species of Staphylococcus or Streptococcus (milder clinical signs). Noninfected (control) quarters of cows having coliform bacteria-infected quarters had slightly increased mean Lf concentrations, where Lf concentration in contral quarters of cows having quarters infected with gram-positive organisms remained unchanged.
Behavioral Activity of Catnip (Lamiaceae) Essential Oil Components to the German Cockroach (Blattodea: Blattellidae) (2002)

The essential oil of catnip, Nepeta cataria L., contains two isomers of nepetalactone, E,Z-and Z,E-nepetalactone, and was tested for repellent activity to adult male German cockroaches, Blattella germanica (L.), in a choice-test arena. The two isomers of nepetalactone were purified by using preparative thin-layer chromatography and tested for behavioral activity in the choice-test arena. Significant differences due to concentration were detected by analysis of variance, and the responses were compared by least-squared means analysis. The activities of the essential oil and purified isomers were compared with N,NA-diethyl-3-methylbenzamide (DEET) by a paired t-test. E,Z-Nepetalactone was the most active of the compounds tested, being significantly more active to this species than equivalent doses of DEET, the essential oil, or Z,E-nepetalactone. Antennectomized insects showed no response to concentrations that were active against intact insects.
An AML1/ETO fusion transcript is consistently detected by RNA-based polymerase chain reaction in acute myelogenous leukemia containing the (8;21)(q22;q22) translocation (1993)

The 8;21 translocation is one of the most common chromosomal translocations in acute myelogenous leukemia (AML), accounting for 40% of pediatric AML with French-American-British (FAB)-M2 morphology. The chromosomal breakpoints have recently been identified at the molecular level and shown to involve the AML1 gene on chromosome 21 and the ETO gene on chromosome 8. Translocation results in the consistent fusion of these genes on the der(8) chromosome, resulting in the production of a novel chimeric gene and message. Using oligonucleotide primers derived from the AML1 and ETO cDNAs, we were able to amplify a specific fusion transcript from 26 of 26 patients with t(8;21) by a reverse transcriptase polymerase chain reaction (PCR) approach. DNA fragments of identical size were generated from each case including two with complex translocations. Studies on the sensitivity and specificity of this approach show that PCR analysis can be used as a rapid, accurate, and sensitive means for detecting this chromosomal abnormality, and for following the patients' response to therapy.
A Universal Approach to Eliminate Antigenic Properties of Alpha-Gliadin Peptides in Celiac Disease (2010)

Celiac disease is caused by an uncontrolled immune response to gluten, a heterogeneous mixture of wheat storage proteins, including the α-gliadins. It has been shown that α-gliadins harbor several major epitopes involved in the disease pathogenesis. A major step towards elimination of gluten toxicity for celiac disease patients would thus be the elimination of such epitopes from α-gliadins. We have analyzed over 3,000 expressed α-gliadin sequences from 11 bread wheat cultivars to determine whether they encode for peptides potentially involved in celiac disease. All identified epitope variants were synthesized as peptides and tested for binding to the disease-associated HLA-DQ2 and HLA-DQ8 molecules and for recognition by patient-derived α-gliadin specific T cell clones. Several specific naturally occurring amino acid substitutions were identified for each of the α-gliadin derived peptides involved in celiac disease that eliminate the antigenic properties of the epitope variants. Finally, we provide proof of principle at the peptide level that through the systematic introduction of such naturally occurring variations α-gliadins genes can be generated that no longer encode antigenic peptides. This forms a crucial step in the development of strategies to modify gluten genes in wheat so that it becomes safe for celiac disease patients. It also provides the information to design and introduce safe gluten genes in other cereals, which would exhibit improved quality while remaining safe for consumption by celiac disease patients.