gebhart/patrepeval huggingface dataset:
Brønsted Guanidine Acid−Base Ionic Liquids:  Novel Reaction Media for the Palladium-Catalyzed Heck Reaction (2006)

[reaction: see text]. Brønsted acid-base ionic liquids (GILs) based on guanidine and acetic acid are efficient reaction media for palladium-catalyzed Heck reactions. They offer the advantages of high activity and reusability. GIL2 plays multiple roles in the reaction: it could act as solvent, as a strong base to facilitate beta-hydride elimination, and as a ligand to stabilize activated Pd species.
The strength of the chemotactic response to a CCR5 binding chemokine is determined by the level of cell surface CCR5 density (2006)

We have shown that the intensity of expression of the C-C chemokine receptor CCR5 at the single CD4(+) cell level strongly determines the efficiency of its function as a coreceptor for human immunodeficiency virus type 1. By analogy, we examined if the number of CCR5 molecules at the cell surface might determine its chemotactic response to CCR5 ligands. To test this hypothesis, we measured by flow cytometry the migration of primary human T cells towards the CCR5-binding chemokine CCL5 in vitro. First, we observed a dose-dependent blockage of this migration exerted by an anti-CCR5 monoclonal antibody. Second, we sorted peripheral blood mononuclear cells into five subpopulations expressing various cell surface CCR5 densities, and observed a correlation between the intensity of migration towards CCL5 and the level of CCR5 expression on these subpopulations. Third, we transduced CCR5(+) peripheral blood mononuclear cells with the CCR5 gene, and observed that the CCR5 over-expression induced an over-migration towards CCL5. Finally, we observed in healthy donors a correlation between the chemotactic response of peripheral blood CD8(+) T cell to CCL5 and their level of surface CCR5 expression. T-cell surface CCR5 density, which is constant over time for a given individual, but varies drastically among individuals, might therefore be an important personal determinant of T-cell migration in many biological situations where CCR5-binding chemokines play a role, such as graft rejection, T helper 1-mediated auto-immune diseases, and infectious diseases involving CCR5. Moreover, our data highlight the therapeutic potential of CCR5 antagonists in these situations.
Characterization of the Oxidative Metabolites of 17β-Estradiol and Estrone Formed by 15 Selectively Expressed Human Cytochrome P450 Isoforms (2003)

We systematically characterized the oxidative metabolites of 17beta-estradiol and estrone formed by 15 human cytochrome P450 (CYP) isoforms. CYP1A1 had high activity for 17beta-estradiol 2-hydroxylation, followed by 15alpha-, 6alpha-, 4-, and 7alpha-hydroxylation. However, when estrone was the substrate, CYP1A1 formed more 4-hydroxyestrone than 15alpha- or 6alpha-hydroxyestrone, with 2-hydroxyestrone as the major metabolite. CYP1A2 had the highest activity for the 2-hydroxylation of both 17beta-estradiol and estrone, although it also had considerable activity for their 4-hydroxylation (9-13% of 2-hydroxylation). CYP1B1 mainly catalyzed the formation of catechol estrogens, with 4-hydroxyestrogens predominant. CYP2A6, 2B6, 2C8, 2C9, 2C19, and 2D6 each showed a varying degree of low catalytic activity for estrogen 2-hydroxylation, whereas CYP2C18 and CYP2E1 did not show any detectable estrogen-hydroxylating activity. CYP3A4 had strong activity for the formation of 2-hydroxyestradiol, followed by 4-hydroxyestradiol and an unknown polar metabolite, and small amounts of 16alpha- and 16beta-hydroxyestrogens were also formed. The ratio of 4- to 2-hydroxylation of 17beta-estradiol or estrone with CYP3A4 was 0.22 or 0.51, respectively. CYP3A5 had similar catalytic activity for the formation of 2- and 4- hydroxyestrogens. Notably, CYP3A5 had an unusually high ratio of 4- to 2-hydroxylation of 17beta-estradiol or estrone (0.53 or 1.26, respectively). CYP3A4 and 3A5 also catalyzed the formation of nonpolar estrogen metabolite peaks (chromatographically less polar than estrone). CYP3A7 had a distinct catalytic activity for the 16alpha-hydroxylation of estrone, but not 17beta-estradiol. CYP4A11 had little catalytic activity for the metabolism of 17beta-estradiol and estrone. In conclusion, many human CYP isoforms are involved in the oxidative metabolism of 17beta-estradiol and estrone, with a varying degree of catalytic activity and distinct regioselectivity.
UTRdb and UTRsite: a collection of sequences and regulatory motifs of the untranslated regions of eukaryotic mRNAs (2004)

The 5' and 3' untranslated regions of eukaryotic mRNAs play crucial roles in the post-transcriptional regulation of gene expression through the modulation of nucleo-cytoplasmic mRNA transport, translation efficiency, subcellular localization and message stability. UTRdb is a curated database of 5' and 3' untranslated sequences of eukaryotic mRNAs, derived from several sources of primary data. Experimentally validated functional motifs are annotated (and also collated as the UTRsite database) and cross-links to genomic and protein data are provided. The integration of UTRdb with genomic and protein data has allowed the implementation of a powerful retrieval resource for the selection and extraction of UTR subsets based on their genomic coordinates and/or features of the protein encoded by the relevant mRNA (e.g. GO term, PFAM domain, etc.). All internet resources implemented for retrieval and functional analysis of 5' and 3' untranslated regions of eukaryotic mRNAs are accessible at http://www.ba.itb.cnr.it/UTR/.
Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours (2001)

Cancer is an epigenetic disease at the same level that it can be considered a genetic disease. In fact, epigenetic changes, particularly DNA methylation, are susceptible to change and are excellent candidates to explain how certain environmental factors may increase the risk of cancer. The delicate organization of methylation and chromatin states that regulates the normal cellular homeostasis of gene expression patterns becomes unrecognizable in the cancer cell. The genome of the transformed cell undergoes simultaneously a global genomic hypomethylation and a dense hypermethylation of the CpG islands associated with gene regulatory regions. These dramatic changes may lead to chromosomal instability, activation of endogenous parasitic sequences, loss of imprinting, illegitimate expression, aneuploidy, and mutations, and may contribute to the transcriptional silencing of tumour suppressor genes. The hypermethylation-associated inactivation affects virtually all of the pathways in the cellular network, such as DNA repair (hMLH1, BRCA1, MGMT, em leader), the cell cycle (p16(INK4a), p14(ARF), p15(INK4b), ...), and apoptosis (DAPK, APAF-1, ...). The aberrant CpG island methylation can also be used as a biomarker of malignant cells and as a predictor of their behaviour, and may constitute a good target for future therapies.
Evolving Landscape of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (2016)

Recognition of the role and importance of driver mutations in malignancy has had a major impact on the management approach for many cancers. In the case of non–small-cell lung cancer, our understanding of molecular alterations has resulted in significant advances in the treatment of subgroups of patients, such as those whose tumors have an EFGR mutation or ALK or ROS-1 gene rearrangements. For tumors with sensitizing EGFR mutations, there is strong clinical evidence that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) such as gefitinib, erlotinib, or afatinib significantly prolong progression-free survival (PFS) compared with platinum doublet chemotherapy. 1-4 Therefore, an EGFRTKIisconsideredthestandardofcareinthe first-linetreatment of EGFR-mutant lung cancer. However, it has been unclear whether there are important differences between the two first-generation EGFR inhibitors erlotinib and gefitinib because of a lack of direct comparative data. In the absence of data, the choice of agent has been largely a matter of physician or patient preference. The study by Urata et al 5 helps make the choice more rational. Initial evaluation of the first-generation EGFR TKIs erlotinib
The Homograft Reaction (1957)

Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and ...Read More
Attenuation of Bleomycin-induced Pulmonary Fibrosis by Follistatin (2005)

Follistatin is effective in treating acute lung injury and BLM-induced fibrosis by blocking the actions of activin and transforming growth factor-beta.
Comparison of the carbohydrate-binding specificities of cholera toxin and Escherichia coli heat-labile enterotoxins LTh-I, LT-IIa, and LT-IIb (1988)

The heat-labile enterotoxins of Vibrio cholerae and Escherichia coli are related in structure and function. They are oligomers consisting of A and B polypeptide subunits. They bind to gangliosides, and they activate adenylate cyclase. The toxins form two antigenically distinct groups; members of each group cross-react but are not necessarily identical. Serogroup I includes cholera toxin (CT) and type I heat-labile enterotoxin (LT-I) of E. coli. LTh-I and LTp-I are antigenic variants of LT-I produced by strains of E. coli from humans and pigs, respectively. Serogroup II contains the type II heat-labile enterotoxin (LT-II) of E. coli. Two antigenic variants designated LT-IIa and LT-IIb have been described. The binding of CT, LTh-I, LT-IIa, and LT-IIb to gangliosides was analyzed by immunostaining thin-layer chromatograms and by solid-phase radioimmunoassay. The four toxins have different glycolipid-binding specificities. LTh-I and CT bind strongly to ganglioside GM1 and less strongly to ganglioside GD1b. However, LTh-I, unlike CT, also binds weakly to GM2 and asialo GM1. LTh-I, like CT, probably binds to the terminal sugar sequence Gal beta 1-3GalNAc beta 1-4(NeuAc alpha 2-3)Gal . . ., where GalNAc is N-acetylgalactosamine and NeuAc is N-acetylneuraminic acid. LT-IIa probably binds to the same sugar sequence to which CT and LTh-I bind, with the additional contribution to binding of a second NeuAc as in GD1b and GD2. Also, LT-IIa must bind the Gal beta 1-3GalNAc . . . sequence in such a way that its binding is relatively unaffected by attachment of NeuAc to the terminal galactose residue as in GD1a, GT1b, and GQ1b. LT-IIb probably binds to the terminal sugar sequence NeuAc alpha 2-3Gal beta 1-4GalNAc . . ., as it binds to gangliosides GD1a and GT1b but not to GM1.
Regulatory Considerations for Novel Gene Therapy Products: A Review of the Process Leading to the First Clinical Lentiviral Vector (2005)

This review is intended to exemplify the roles and responsibilities of the two agencies under the Department of Health and Human Services, the National Institutes of Health and the Food and Drug Administration, that have oversight for human gene transfer clinical protocols, as seen through our experience of bringing a first-in-its-class lentiviral vector to clinical trials. In response to the changing circumstances in gene therapy research between 1999 and 2002, the concerns of these agencies regarding gene therapy have been evolving. This review provides an overview of the major safety concerns regarding insertional oncogenesis, the generation of a replication- competent lentivirus (RCL), and vector mobilization thought to be related to lentiviral vectors, which had to be addressed during the regulatory review process before initiating the clinical trial. Specific monitoring assays to address these concerns were established to test for RCL generation, vector mobilization, persistence of vector-modified cells, and abnormal clonal expansion of modified cells. We hope to provide a basic understanding and appreciation of the regulatory process and major safety concerns, toward providing useful insight to those presently embarking on the development of clinical application of lentiviral vectors.
γ‐AApeptides as a New Class of Peptidomimetics (2016)

Sequence-specific peptidomimetics are molecules that mimic the structure and function of peptides and proteins. With new backbones and molecular frameworks, peptidomimetics are of considerable interest in addressing challenges encountered in chemical biology and biomedical sciences. Based on the γ-PNA backbone, a new class of peptidomimetics - "γ-AApeptides" were recently developed. Both linear and cyclic γ-AApeptides can be synthesized with high efficiency. Compared with α-peptides, γ-AApeptides are resistant to enzymatic degradation, and amendable to diversification with a variety of chemical groups. Moreover, they could mimic primary and secondary structure, as well as the function of peptides, and show promise in biological applications, such as the development of new agents combating bacteria, cancer, and Alzheimer's disease. A few research outcomes of γ-AApeptides are highlighted in this Concept article, and a future perspective is also proposed.
LARGE-SCALE PREPARATION OF HIGHLY PURIFIED PYROGEN-FREE HUMAN GROWTH HORMONE FOR CLINICAL USE (1979)

A method is described for the large-scale isolation of highly purified human growth hormone for therapeutic use. The hormone was extracted from frozen pituitary glands under mildly alkaline conditions. Purification was effected by gel filtration and ion-exchange chromatography. The final product was pyrogen-free and had a potency of 2.5 i.u./mg measured by bioassay against the current international standard. The yield of growth hormone/gland was approximately 5 mg.
Human Epidermal Growth Factor Enhances Healing of Diabetic Foot Ulcers (2003)

Our data support the contention that application of hEGF-containing cream, in addition to good foot care from a multidisciplinary team, significantly enhances diabetic foot ulcer wound healing and reduces the healing time.
Rates of Movement of Threatened Bird Species between IUCN Red List Categories and toward Extinction (2008)

In recent centuries bird species have been deteriorating in status and becoming extinct at a rate that may be 2-3 orders of magnitude higher than in prehuman times. We examined extinction rates of bird species designated critically endangered in 1994 and the rate at which species have moved through the IUCN (World Conservation Union) Red List categories of extinction risk globally for the period 1988-2004 and regionally in Australia from 1750 to 2000. For Australia we drew on historical accounts of the extent and condition of species habitats, spread of invasive species, and changes in sighting frequencies. These data sets permitted comparison of observed rates of movement through the IUCN Red List categories with novel predictions based on the IUCN Red List criterion E, which relates to explicit extinction probabilities determined, for example, by population viability analysis. The comparison also tested whether species listed on the basis of other criteria face a similar probability of moving to a higher threat category as those listed under criterion E. For the rate at which species moved from vulnerable to endangered, there was a good match between observations and predictions, both worldwide and in Australia. Nevertheless, species have become extinct at a rate that, although historically high, is 2 (Australia) to 10 (globally) times lower than predicted. Although the extinction probability associated with the critically endangered category may be too high, the shortfall in realized extinctions can also be attributed to the beneficial impact of conservation intervention. These efforts may have reduced the number of global extinctions from 19 to 3 and substantially slowed the extinction trajectory of 33 additional critically endangered species. Our results suggest that current conservation action benefits species on the brink of extinction, but is less targeted at or has less effect on moderately threatened species.
An RNA–Deaminase Conjugate Selectively Repairs Point Mutations (2012)

Checking for mistakes: By conjugating a catalytic domain with a guide RNA, deamination activity can be harnessed to repair a specific codon on mRNA. This method can be used for the highly selective repair of point mutations in mRNA by site-selective editing.
Defining the Antigen-Specific T-Cell Response to Vaccination and Poly(I:C)/TLR3 Signaling (2005)

Poly(I:C), a synthetic double-stranded RNA polymer and a TLR3 agonist, can be used as a vaccine adjuvant to enhance adaptive immunity. However, the antigen-specific CD8 T-cell response to peptide vaccination and poly(I:C) has not been clearly defined. Here, the authors characterized the antigen-specific CD8 T-cell response to peptide vaccination and poly(I:C) and specifically addressed the hypothesis that poly(I:C) can enhance antitumor immunity. To define the antigen-specific T-cell response, the authors established a model based on the adoptive transfer of T cells from the OT-1 T-cell receptor transgenic mouse. In this model, vaccination with peptide alone resulted in a limited, transient expansion of antigen-specific CD8 T cells. In contrast, peptide vaccination with concomitant administration of poly(I:C) resulted in a dramatic sustained increase in the number of antigen-specific CD8 T cells. This increase in cell number was associated with an increase in CD8 T-cell function, as defined by specific IFN-gamma and TNF-alpha production, and protection from tumor challenge. The adjuvant effects of poly(I:C) appear to be at least partially dependent on an increase in the transcription of the anti-apoptotic molecules Bcl-3 and Bcl-xL and a concomitant decrease in apoptosis during the contraction phase of the primary T-cell response. In addition, administration of poly(I:C) enhanced the response to a nonimmunogenic self-antigen in a dendritic cell vaccine-based vaccine strategy. Collectively, these results confirm the potential of poly(I:C) as a vaccine adjuvant and suggest that targeting of TLR3 is likely to be a valuable addition to peptide-based vaccination strategies.
Structure of the genes of two homologous intracellularly heterotopic isoenzymes (1990)

The genes of mitochondrial and cytosolic aspartate aminotransferase of chicken were cloned and sequenced. In both genes nine exons encode the mature enzyme. The additional exon for the N-terminal presequence that directs mitochondrial aspartate aminotransferase into the mitochondria is separated by the largest intron from the rest of the gene. A comparison of the two genes of chicken with the aspartate aminotransferase genes of mouse [Tsuzuki, T., Obaru, K., Setoyama, C. & Shimada, K. (1987) J. Mol. Biol. 198, 21-31; Obaru, K., Tsuzuki, T., Setoyama, C. & Shimada, K. (1988) J. Mol. Biol. 200, 13-22] reveals closely similar structures: in the gene of both the mitochondrial and the cytosolic isoenzyme all but one intron positions are conserved in the two species and five introns out of nine are placed at the same positions in all four genes indicating that the introns were in place before the genes of the two isoenzymes diverged. The variant consensus sequence (T/C)11 T(C/T)AG at the 3' splice site of the introns of the genes for nuclear-encoded mitochondrial proteins, which had been deduced from a total of 34 introns [Juretić, N., Jaussi, R., Mattes, U. & Christen, P. (1987) Nucleic Acids Res. 15, 10,083-10,086], was confirmed by including an additional 22 introns into the comparison. The position -4 at the 3' splice site is occupied by base T in 43% of the total 56 introns and appears to be subject to a special evolutionary constraint in this particular group of genes. The following course of evolution of the aspartate aminotransferase genes is proposed. Originating from a common ancestor, the genes of the two isoenzymes intermediarily evolved in separate lineages, i.e. the ancestor eukaryotic and ancestor endosymbiontic cells. When endosymbiosis was established, part of the endosymbiontic genome, including the aspartate aminotransferase gene, was transferred to the nucleus. This process probably led to the conservation of certain splicing factors specific for nuclear-encoded mitochondrial proteins. The presequence for the mitochondrial isoenzyme was acquired by DNA rearrangement. In the eukaryotic lineage, the mitochondrial isoenzyme evolved more slowly than its cytosolic counterpart.
Relationships Between Intravenous Glucose Loads, Insulin Responses and Glucose Disappearance Rate1 (1971)

In order to evaluate the relation between insulin responses, glucose loads and glucose disappearance rate, normal subjects were given glucose doses from 0.5 to 40 g by rapid intravenous injection. A highly linear correlation was seen between dose and the rapidly attained peak plasma glucose level measured as either the mean of the 3- through 5-min (3–5′) absolute (r=+.98) or 3–5′ incremental (Δ) (r=+.98) glucose value, suggesting any of these parameters can be employed as an index of the glucose stimulus. Estimated from the 3–5′ Δ plasma insulin levels, the early insulin response, which has been previously shown to be derived from a functional pool of stored insulin, increased in a nonlinear manner over the entire dosage range. In contrast, the total incremental insulin area increased linearly (r=+.85) with increasing glucose loads, suggesting that the total insulin output proportionally responds to the size of the glucose dose. Glucose tolerance measured as the glucose disappearance rate (Kg) was also a nonlinear function of glucose dose and therefore was highly correlated (r=+.72) with the acute insulin response but less well with the total incremental insulin output. Furthermore, within the 20 g glucose dose, the Kg was highly correlated with the acute insulin response (r=+.66) but not with total insulin output (r=+.04). These observations suggest that the storage pool of readily available insulin is small and finite and the magnitude of the response from this pool is an important determinant of intravenous glucose tolerance (Kg).
Variation and Selection at the CAULIFLOWER Floral Homeotic Gene Accompanying the Evolution of Domesticated Brassica oleracea (2000)

The evolution of plant morphologies during domestication events provides clues to the origin of crop species and the evolutionary genetics of structural diversification. The CAULIFLOWER gene, a floral regulatory locus, has been implicated in the cauliflower phenotype in both Arabidopsis thaliana and Brassica oleracea. Molecular population genetic analysis indicates that alleles carrying a nonsense mutation in exon 5 of the B. oleracea CAULIFLOWER (BoCAL) gene are segregating in both wild and domesticated B. oleracea subspecies. Alleles carrying this nonsense mutation are nearly fixed in B. oleracea ssp. botrytis (domestic cauliflower) and B. oleracea ssp. italica (broccoli), both of which show evolutionary modifications of inflorescence structures. Tests for selection indicate that the pattern of variation at this locus is consistent with positive selection at BoCAL in these two subspecies. This nonsense polymorphism, however, is also present in both B. oleracea ssp. acephala (kale) and B. oleracea ssp. oleracea (wild cabbage). These results indicate that specific alleles of BoCAL were selected by early farmers during the domestication of modified inflorescence structures in B. oleracea.