gebhart/patrepeval huggingface dataset:
A flavonoid chrysin suppresses hypoxic survival and metastatic growth of mouse breast cancer cells (2013)

Tumor hypoxia commonly occurs in solid tumors, and correlates with metastasis. Current cancer therapies are inefficient in curing metastatic disease. Herein, we examined effect of Thai propolis extract and its major constituent, chrysin, on hypoxic survival of 4T1 mouse breast cancer cells in vitro, and investigated its underlying mechanism. In vivo effect of chrysin on metastatic progression of cancer cells was studied, both as a single agent and in combination with another antimetastatic agent, agonistic monoclonal antibody targeting the DR5 TRAIL receptor (DR5 mAb). Thai propolis extract and chrysin decreased survival of 4T1 cells after exposure to hypoxia (1% O2), for 2 days. Immunoblot analysis revealed that chrysin inhibited hypoxia-induced STAT3 phosphorylation without affecting HIF-1α protein level. Chrysin also abrogated hypoxia-induced VEGF gene expression as determined by qRT-PCR. The in vivo effect of chrysin was determined in a spontaneous metastasis mouse model of breast cancer, either alone or in combination with DR5 mAb. Daily oral administration of chrysin in Balb/c mice implanted with 4T1 cells significantly suppressed growth of lung metastatic colonies. Moreover, antimetastatic activity of DR5 mAb was enhanced when given in combination with chrysin. We demonstrate that chrysin has potential in controlling metastatic progression.
Three Microbial Strategies for Plant Cell Wall Degradation (2008)

Cellulolytic bacteria and fungi have been shown to use two different approaches to degrade cellulose. Most aerobic microbes secrete sets of individual cellulases, many of which contain a carbohydrate binding molecule (CBM), which act synergistically on native cellulose. Most anaerobic microorganisms produce large multienzyme complexes called cellulosomes, which are usually attached to the outer surface of the microorganism. Most of the cellulosomal enzymes lack a CBM, but the cohesin subunit, to which they are bound, does contain a CBM. The cellulases present in each class show considerable overlap in their catalytic domains, and processive cellulases (exocellulases and processive endocellulases) are the most abundant components of both the sets of free enzymes and of the cellulosomal cellulases. Analysis of the genomic sequences of two cellulolytic bacteria, Cytophaga hutchinsonii, an aerobe, and Fibrobacter succinogenes, an anaerobe, suggest that these organisms must use a third mechanism. This is because neither of these organisms, encodes processive cellulases and most of their many endocellulase genes do not encode CBMs. Furthermore, neither organism appears to encode the dockerin and cohesin domains that are key components of cellulosomes.
One-Pot Synthesis of Diverse 4-Di(tri)fluoromethyl-3-cyanopyridine-2(1H)-thiones and Their Utilities in the Cascade Synthesis of Annulated Heterocycles (2008)

Diverse substituted 4-di(tri)fluoromethyl-3-cyanopyridine-2(1H)-thiones were synthesized via the Claisen condensation of alpha-methyl(methylene)ketones with di(tri)fluoroacetate, followed by the immediate Thorpe-Guareschi reaction of the preformed di(tri)fluoromethyl-1,3-diketones with cyanothioacetamide. The procedure allows facile synthesis of the di(tri)flouromethylated pyridine-2(1H)-thiones in 50-95% yields, without the need for isolation and purification of intermediates. Resultant 4-di(tri)fluoromethyl-3-cyanopyridine-2(1 H)-thiones were subsequently utilized in domino reactions to produce first various substituted thieno[2,3-b]pyridines and, then, thienopyridines polyannulated with pyridine, pyrimidine, benzodiazocine, diazepine, and pyran rings.
The Single Particles, Clusters and Biomolecules and Serial Femtosecond Crystallography instrument of the European XFEL: initial installation (2019)

The European X-ray Free-Electron Laser (FEL) became the first operational high-repetition-rate hard X-ray FEL with first lasing in May 2017. Biological structure determination has already benefitted from the unique properties and capabilities of X-ray FELs, predominantly through the development and application of serial crystallography. The possibility of now performing such experiments at data rates more than an order of magnitude greater than previous X-ray FELs enables not only a higher rate of discovery but also new classes of experiments previously not feasible at lower data rates. One example is time-resolved experiments requiring a higher number of time steps for interpretation, or structure determination from samples with low hit rates in conventional X-ray FEL serial crystallography. Following first lasing at the European XFEL, initial commissioning and operation occurred at two scientific instruments, one of which is the Single Particles, Clusters and Biomolecules and Serial Femtosecond Crystallography (SPB/SFX) instrument. This instrument provides a photon energy range, focal spot sizes and diagnostic tools necessary for structure determination of biological specimens. The instrumentation explicitly addresses serial crystallography and the developing single particle imaging method as well as other forward-scattering and diffraction techniques. This paper describes the major science cases of SPB/SFX and its initial instrumentation - in particular its optical systems, available sample delivery methods, 2D detectors, supporting optical laser systems and key diagnostic components. The present capabilities of the instrument will be reviewed and a brief outlook of its future capabilities is also described.
Isolation and sequence of complementary DNA encoding human extracellular superoxide dismutase. (1987)

A complementary DNA (cDNA) clone from a human placenta cDNA library encoding extracellular superoxide dismutase (EC-SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) has been isolated and the nucleotide sequence determined. The cDNA has a very high G+C content. EC-SOD is synthesized with a putative 18-amino acid signal peptide, preceding the 222 amino acids in the mature enzyme, indicating that the enzyme is a secretory protein. The first 95 amino acids of the mature enzyme show no sequence homology with other sequenced proteins and there is one possible N-glycosylation site (Asn-89). The amino acid sequence from residues 96-193 shows strong homology (approximately 50%) with the final two-thirds of the sequences of all known eukaryotic CuZn SODs, whereas the homology with the P. leiognathi CuZn SOD is clearly lower. The ligands to Cu and Zn, the cysteines forming the intrasubunit disulfide bridge in the CuZn SODs, and the arginine found in all CuZn SODs in the entrance to the active site can all be identified in EC-SOD. A comparison with bovine CuZn SOD, the three-dimensional structure of which is known, reveals that the homologies occur in the active site and the divergences are in the part constituting the subunit contact area in CuZn SOD. Amino acid sequence 194-222 in the carboxyl-terminal end of EC-SOD is strongly hydrophilic and contains nine amino acids with a positive charge. This sequence probably confers the affinity of EC-SOD for heparin and heparan sulfate. An analysis of the amino acid sequence homologies with CuZn SODs from various species indicates that the EC-SODs may have evolved from the CuZn SODs before the evolution of fungi and plants.
Defects in Tendon, Ligament, and Enthesis in Response to Genetic Alterations in Key Proteoglycans and Glycoproteins: A Review (2013)

This review summarizes the genetic alterations and knockdown approaches published in the literature to assess the role of key proteoglycans and glycoproteins in the structural development, function, and repair of tendon, ligament, and enthesis. The information was collected from (i) genetically altered mice, (ii) in vitro knockdown studies, (iii) genetic variants predisposition to injury, and (iv) human genetic diseases. The genes reviewed are for small leucine-rich proteoglycans (lumican, fibromodulin, biglycan, decorin, and asporin); dermatan sulfate epimerase (Dse) that alters structure of glycosaminoglycan and hence the function of small leucine-rich proteoglycans by converting glucuronic to iduronic acid; matricellular proteins (thrombospondin 2, secreted phosphoprotein 1 (Spp1), secreted protein acidic and rich in cysteine (Sparc), periostin, and tenascin X) including human tenascin C variants; and others, such as tenomodulin, leukocyte cell derived chemotaxin 1 (chondromodulin-I, ChM-I), CD44 antigen (Cd44), lubricin (Prg4), and aggrecan degrading gene, a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 5 (Adamts5). Understanding these genes represents drug targets for disrupting pathological mechanisms that lead to tendinopathy, ligamentopathy, enthesopathy, enthesitis and tendon/ligament injury, that is, osteoarthritis and ankylosing spondylitis.
Dehydroepiandrosterone: An anti‐obesity and anti‐carcinogenic agent (1981)

Long-term treatment of female C3H-Avy/A (obese) and C3H-A/A (non-obese) mice with dehydroepiandrosterone, an adrenal steroid found in subnormal levels in women predisposed to develop breast cancer, reduces weight gain without suppressing appetite and significantly inhibits the development of spontaneous breast cancer. This steroid also antagonizes the capacity of the tumor promoter, 12-0-tetradecanoyl-phorbol-13-acetate, to stimulate 3H-thymidine incorporation in mouse epidermis and in a cultured rat kidney epithelial cell line.
Photocoagulated human retinal pigment epithelial cells produce an inhibitor of vascular endothelial cell proliferation. (1995)

Photocoagulated RPE cells secrete inhibitors of BAEC and BREC proliferation. Molecular size and immunologic properties of these inhibitors correspond to those of TGF-beta 2.
Fluorine-18-fluorodeoxyglucose uptake in pneumonia. (1998)

Whole-body PET imaging with 18F-fluorodeoxyglucose (FDG) has been shown to be effective in distinguishing benign and malignant pulmonary disease. Mild elevations in FDG uptake with standardized uptake values (SUVs) less than 2.5 have been reported in benign lesions, including pneumonia. We report a case of presumed bacterial pneumonia with markedly elevated FDG uptake in a patient with a concomitant squamous cell carcinoma in the contralateral lung. SUV's were similar for both lesions (4.9 and 5.4). This case demonstrates an inflammatory etiology for false-positive FDG PET imaging in the evaluation of focal pulmonary abnormalities.
The Role of CD4 T Cells in the Pathogenesis of Murine AIDS (2006)

LP-BM5, a retroviral isolate, induces a disease featuring retrovirus-induced immunodeficiency, designated murine AIDS (MAIDS). Many of the features of the LP-BM5-induced syndrome are shared with human immunodeficiency virus-induced disease. For example, CD4 T cells are critical to the development of MAIDS. In vivo depletion of CD4 T cells before LP-BM5 infection rendered genetically susceptible B6 mice MAIDS resistant. Similarly, MAIDS did not develop in B6.nude mice. However, if reconstituted with CD4 T cells, B6.nude mice develop full-blown MAIDS. Our laboratory has shown that the interaction of B and CD4 T cells that is central to MAIDS pathogenesis requires ligation of CD154 on CD4 T cells with CD40 on B cells. However, it is not clear which additional characteristics of the phenotypically and functionally heterogeneous CD4 T-cell compartment are required. Here, in vivo adoptive transfer experiments using B6.nude recipients are employed to compare the pathogenic abilities of CD4 T-cell subsets defined on the basis of cell surface phenotypic or functional differences. Th1 and Th2 CD4 T cells equally supported MAIDS induction. The rare Thy1.2(-) CD4 subset that expands upon LP-BM5 infection was not necessary for MAIDS. Interestingly, CD45RB(low) CD4 T cells supported significantly less disease than CD45RB(high) CD4 T cells. Because the decreased MAIDS pathogenesis could not be attributed to inhibition by CD45RB(low) CD25(+) natural T-regulatory cells, an intrinsic property of the CD45RB(low) cells appeared responsible. Similarly, there was no evidence that natural T-regulatory cells played a role in LP-BM5-induced pathogenesis in the context of the intact CD4 T-cell population.
Recent Advances in the Discovery and Delivery of TLR7/8 Agonists as Vaccine Adjuvants (2018)

The need for new adjuvants is absolutely cardinal to the development of new vaccines and to further optimizing current immunization approaches. However, only a few classes of adjuvants are presently incorporated in vaccines approved for human use. Recent advances in the discovery and delivery of TLR agonists as vaccine adjuvants have begun to open up a new toolbox for vaccinologists. At the forefront of this movement is the use of synthetic small molecule TLR7/8 agonist-based adjuvants. In this review, we emphasize the importance of vaccine formulation science in driving recent developments in TLR7/8 adjuvanticity, summarize some of the most current and notable studies in this field, and discuss desirable attributes of next generation TLR7/8 adjuvants for use in enhancing vaccine responses in vulnerable populations, such as the very young. Finally, we explore advances that may further edge the development of TLR7/8 adjuvant-based vaccine formulations toward clinical human evaluation.
Mobility Control Using CO2 Forms (1989)

Abstract Mobility reduction caused by CO2 foams that are "stable" or "unstable" in the bulk phase was studied in Berea sandstone and San Andres carbonate outcrop cores at l00°F and 2000 psi. Depending on hydrophilicity, some surfactants led to foams having a favorable dependence on permeability and oil saturation whereas another did not. Foam mobility was found "shear thinning" at high flow rates and "shear thickening" at low rates. Bubble coalescence was investigated in relation to snap-off, transport and trapping.
Design, Synthesis, and Analysis of Disulfide Cross-Linked DNA Duplexes (1996)

The design, synthesis, and analysis of analogs of d(CGCGAATTCGCG)2 possessing one or two intrahelical disulfide cross-links is reported. The cross-linked oligomers were prepared by first synthesizing duplexes where the 3‘- and 5‘-terminal bases of the parent sequence were replaced with N3-thioethylthymidine. Following deprotection and purification, air oxidation afforded the desired cross-linked constructs in high yield. Analysis of both the oxidized (disulfide cross-linked) and reduced (thiol modified) duplexes by UV, circular dichroism, and NMR spectroscopies along with susceptibility to EcoRI cleavage indicates that the modifications are not structurally perturbing. Optical thermal denaturation and differential scanning calorimetry measurements suggest that introducing disulfide cross-link(s) into d(CGCGAATTCGCG)2 does, however, cause two fundamental changes. First, the cross-link(s) increase the thermal stability of the modified duplexes by changing the molecularity of denaturation without an increase in enthalpy. Second, the disulfide cross-link traps one of the conformations of the conformationally heterogeneous parent molecule resulting in a conformationally homogeneous system. Both of these features are themselves unique and will be important for further applications of disulfide cross-linked oligomers such as these in studies of nucleic acid structure and function.
Content-based Image Retrieval (2000)

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A randomized, controlled trial of IL-10 in humans. Inhibition of inflammatory cytokine production and immune responses. (1995)

In vitro, IL-10 inhibits T cell proliferation and LPS-induced monocyte production of IL-1, TNF-alpha, IL-6, and IL-8. We studied the safety and immunomodulatory effects of IL-10 administration in humans. Seventeen healthy volunteers received a single i.v. bolus injection of either human IL-10 (1, 10, or 25 micrograms/kg) or placebo. Routine safety parameters, lymphocyte phenotypes, T cell proliferative responses, and stimulus-induced cytokine production were assessed before and 3, 6, 24, and 48 h after injection. There were no adverse symptoms or signs after IL-10 administration. A transient neutrophilia and monocytosis that peaked at 6 h (45-160% above base line) was observed. However, lymphocyte counts fell by 25% 3 and 6 h after the injection (p < 0.01). In particular, lymphocytes expressing the T cell surface markers CD2, CD3, CD4, CD7, and CD8 were significantly decreased. Mitogen-induced T cell proliferation was suppressed by up to 50% (p < 0.01) in the two higher dose groups. Significant dose-dependent inhibition (65-95%) of TNF-alpha and IL-1 beta production from whole blood stimulated ex vivo with endotoxin occurred after each dose of IL-10. In contrast, there was no reduction in the production of their respective antagonists, TNF soluble receptor p55 or IL-1 receptor antagonist. We conclude that a single intravenous injection of IL-10 is safe in humans, has inhibitory effects on T cells, and suppresses production of the pro-inflammatory cytokines TNF-alpha and IL-1 beta.
Efficient Construction of a Doubly Functionalized Trisoxazole Derivative Relevant to the Synthesis of the Novel Telomerase Inhibitor Telomestatin and its Analogues (2006)

An efficient construction of a suitably functionalized trisoxazole derivative related to telomestatin was developed from l-serine, which involved three sequential oxazoline cyclization-oxidation steps in an overall yield of 11% in a linear sequence of twelve steps.
AAV9-mediated central nervous system–targeted gene delivery via cisterna magna route in mice (2016)

Current barriers to the use of adeno-associated virus serotype 9 (AAV9) in clinical trials for treating neurological disorders are its high expression in many off-target tissues such as liver and heart, and lack of cell specificity within the central nervous system (CNS) when using ubiquitous promoters such as human cytomegalovirus (CMV) or chicken-β-actin hybrid (CAG). To enhance targeting the transgene expression in CNS cells, self-complementary (sc) AAV9 vectors, scAAV9-GFP vectors carrying neuronal Hb9 and synapsin 1, and nonspecific CMV and CAG promoters were constructed. We demonstrate that synapsin 1 and Hb9 promoters exclusively targeted neurons in vitro, although their strengths were up to 10-fold lower than that of CMV. In vivo analyses of mouse tissue after scAAV9-GFP vector delivery via the cisterna magna revealed a significant advantage of synapsin 1 promoter over both Hb9 variants in targeting neurons throughout the brain, since Hb9 promoters were driving gene expression mainly within the motor-related areas of the brain stem. In summary, this study demonstrates that cisterna magna administration is a safe alternative to intracranial or intracerebroventricular vector delivery route using scAAV9, and introduces a novel utility of the Hb9 promoter for the targeted gene expression for both in vivo and in vitro applications.
The erythroid protein cGATA-1 functions with a stage-specific factor to activate transcription of chromatin-assembled beta-globin genes. (1993)

The chick beta-globin gene is regulated developmentally within erythroid cells by the interaction of multiple proteins with the promoter and the 3' enhancer. These interactions are correlated with changes in chromatin structure, which are characteristic of the actively expressed gene. Using in vitro chromatin assembly and transcription with staged erythroid extracts, we have determined the critical proteins required to activate expression of nucleosome-reconstituted beta-globin genes. These genes contain a specialized TATA box at -30 (GATA) through which the erythroid-restricted protein cGATA-1 and TFIID both function to regulate different steps in beta-globin expression. We find that TBP (TATA-binding protein) alone can activate transcription of beta-globin chromatin templates from promoters mutated to a canonical TATA box but is ineffective on those containing the normal -30 GATA site. The occupancy of this site by cGATA-1 also fails to generate efficient expression of beta-globin chromatin unless combined with a stage-specific protein, NF-E4, that binds to an adjacent site. However, NF-E4 does not function with TBP to derepress nucleosome-assembled beta-globin genes. We propose that the developmental regulation of beta-globin expression is achieved, in part, by the requirement of an erythroid protein and a stage-specific factor, rather than TBP, to activate chromatin through a specialized TATA box.
Soil Ingestion by Cattle Grazing Crested Wheatgrass (1977)

Soil ingestion rates were determined using four 350-kg esophageal fistulated heifers. Soil concentrations in feces, as determined indirectly by titanium analysis, averaged 14 and 20% in June and August, respectively. Calculated soil ingestion rates were 0.73 and 0.99 kg/animal-day for the two respective periods.
Identification and Analysis of a Gene from Calendula officinalis Encoding a Fatty Acid Conjugase (2001)

Two homologous cDNAs, CoFad2 and CoFac2, were isolated from a Calendula officinalis developing seed by a polymerase chain reaction-based cloning strategy. Both sequences share similarity to FAD2 desaturases and FAD2-related enzymes. In C. officinalis plants CoFad2 was expressed in all tissues tested, whereas CoFac2 expression was specific to developing seeds. Expression of CoFad2 cDNA in yeast (Saccharomyces cerevisiae) indicated it encodes a Delta12 desaturase that introduces a double bond at the 12 position of 16:1(9Z) and 18:1(9Z). Expression of CoFac2 in yeast revealed that the encoded enzyme acts as a fatty acid conjugase converting 18:2(9Z, 12Z) to calendic acid 18:3(8E, 10E, 12Z). The enzyme also has weak activity on the mono-unsaturates 16:1(9Z) and 18:1(9Z) producing compounds with the properties of 8,10 conjugated dienes.
A study of the ferrous ion-initiated SRN1 reactions of halogenoarenes with tert-butyl acetate and N-acylmorpholine enolates (1993)

A detailed preparative study is reported of the ferrous ion-initiated SRN1 reactions of a range of halogenoarenes with the sodium enolates of tert-butyl acetate, N-acetylmorpholine and a number of higher N-acylmorpholines. Smooth and rapid substitution occurs in many cases, and good to excellent yields were obtained of arylacetic esters or acids, arylacetamides and arylalkanamides. The broad scope and limitations of the process have been defined, and the possible role of the ferrous ion is discussed.