gebhart/patrepeval huggingface dataset:
Stat3 activation in human endometrial and cervical cancers (2007)

The activation of signal transducer and activator of transcription 3 (Stat3) has been implicated in the oncogenesis of cancer and is regarded as a novel target for cancer therapy. Stat3 is classified as a proto-oncogene, because an activated form of Stat3 can mediate oncogenic transformation in cultured cells and tumour formation in nude mice. The constitutive activation of Stat3 has been frequently detected in various types of human cancers. However, the constitutive activation of Stat3 in endometrial and cervical cancers has not been studied. We examined tyrosine phosphorylation of Stat3 (activated form of Stat3) in multiple endometrial and cervical cancer tissues using tissue microarray slides as well as cancer cell lines to explore the possible activation of Stat3. Our results indicated that elevated phosphorylation of Stat3 was detected in cervical and endometrial cancer cell lines. Our results also showed that elevated levels of phosphorylation of Stat3 protein were detected in the endometrial and cervical cancer specimens. This is the first study to demonstrate that Stat3 is activated in human endometrial and cervical cancer tissues. Immunohistochemical staining showed that activated Stat3 is associated with increased expression of downstream antiapoptotic genes, Bcl-xL, survivin, and Mcl-1 in these tissues. Expression of a dominant-negative Stat3 mutant using adenovirus-mediated gene transfer inhibited cell growth and induced apoptosis in HeLa and SiHa cervical cancer cell lines expressing elevated levels of Stat3 phosphorylation. Further, a JAK/Stat3 small molecular inhibitor, JSI-124, induced apoptosis more selectively in HeLa and SiHa cancer cell lines than Ishikawa cell line without elevated levels of Stat3 phosphorylation. These results indicate that Stat3 is activated in human endometrial and cervical cancers and the inhibition of constitutive Stat3 signaling may be an effective target for cancer intervention in these two cancers.
Gd(iii) and Mn(ii) complexes for dynamic nuclear polarization: small molecular chelate polarizing agents and applications with site-directed spin labeling of proteins (2016)

We investigate complexes of two paramagnetic metal ions Gd<sup>3+</sup> and Mn<sup>2+</sup> to serve as polarizing agents for solid-state dynamic nuclear polarization (DNP) of <sup>1</sup>H, <sup>13</sup>C, and <sup>15</sup>N at magnetic fields of 5, 9.4, and 14.1 T. Both ions are half-integer high-spin systems with a zero-field splitting and therefore exhibit a broadening of the m<sub>S</sub> = -1/2 ↔ +1/2 central transition which scales inversely with the external field strength. We investigate experimentally the influence of the chelator molecule, strong hyperfine coupling to the metal nucleus, and deuteration of the bulk matrix on DNP properties. At small Gd-DOTA concentrations the narrow central transition allows us to polarize nuclei with small gyromagnetic ratio such as <sup>13</sup>C and even <sup>15</sup>N via the solid effect. We demonstrate that enhancements observed are limited by the available microwave power and that large enhancement factors of >100 (for <sup>1</sup>H) and on the order of 1000 (for <sup>13</sup>C) can be achieved in the saturation limit even at 80 K. At larger Gd(iii) concentrations (≥10 mM) where dipolar couplings between two neighboring Gd<sup>3+</sup> complexes become substantial a transition towards cross effect as dominating DNP mechanism is observed. Furthermore, the slow spin-diffusion between <sup>13</sup>C and <sup>15</sup>N, respectively, allows for temporally resolved observation of enhanced polarization spreading from nuclei close to the paramagnetic ion towards nuclei further removed. Subsequently, we present preliminary DNP experiments on ubiquitin by site-directed spin-labeling with Gd<sup>3+</sup> chelator tags. The results hold promise towards applications of such paramagnetically labeled proteins for DNP applications in biophysical chemistry and/or structural biology.
A Review of Proteotlytic Enzymes from Marine Organisms and Their Application in the Food Industry (1992)

Proteolytic enzyme are widely used as food processing aids. In recent years, proteolytic enzymes from marine organisms have been used as process aids. Other possible uses of enzymes form marine animals in the food industry are based on the unique properties of these enzymes. Examples of unique properties include ease of heat denaturation, high molecular activity at low temperatures and ability to catalyze hydrolysis of native proteins. The possible advantage of using an enzyme form a marine organism in specific applications rather than a conventional plant, animal or microbial source is discussed.
Cell-free fetal DNA and RNA in maternal blood: implications for safer antenatal testing (2009)

#### Summary points

The landmark discovery that cell-free fetal DNA circulates in maternal blood during pregnancy has stimulated research worldwide into many potential applications in obstetric care.1 Improvements in molecular genetic technology over the same period have enabled the translation of cell-free fetal DNA testing into clinical practice for early non-invasive prenatal identification of some genetic traits. However, complex wider ethical, legal, and social problems associated with the technology, as well as implications for clinical and laboratory services, still need careful consideration. This article gives an overview of recent developments in cell-free fetal nucleic acid technology and its implications for non-invasive prenatal diagnosis and screening.

#### Sources and selection criteria

We searched PubMed, the Cochrane Collaboration, and Science Direct using the terms “non-invasive prenatal diagnosis” and “free fetal DNA” (and common variations), in addition to using personal archives of references. We also led a working group of experts and key stakeholders in the United Kingdom to review the area and make recommendations for implementation of this technology in the NHS.

Prenatal screening and diagnosis form a routine part of antenatal …
Efficient transformation and regeneration of rice small cell groups. (1991)

Transgenic plants have been regenerated from small cell groups of rice using a simpler, faster, and more efficient method than used previously (e.g., protoplast transformation and regeneration methods). Small cell groups of 50-100 cells were prepared from established suspension cultures of rice cell lines. Transformation of small cell groups with intact cell walls was carried out with a plasmid harboring the beta-glucuronidase gene and was mediated by polyethylene glycol. Assay of beta-glucuronidase activity indicated that the frequency of transformation was about 7%. beta-Glucuronidase activity was detected in the roots and leaves of plants regenerated from transformed calli. One or two copies of the beta-glucuronidase gene per cell were determined to be integrated into the rice chromosomal DNA isolated from transformed calli. This method of transformation and regeneration is widely applicable to both dicotyledonous and monocotyledonous plants, especially those varieties that are resistant to regeneration from protoplasts.
Design of highly efficient cellulase mixtures for enzymatic hydrolysis of cellulose (2007)

An extremely highly active cellobiohydrolase (CBH IIb or Cel6B) was isolated from Chrysosporium lucknowense UV18-25 culture filtrate. The CBH IIb demonstrated the highest ability for a deep degradation of crystalline cellulose amongst a few cellobiohydrolases tested, including C. lucknowense CBH Ia, Ib, IIa, and Trichoderma reesei CBH I and II. Using purified C. lucknowense enzymes (CBH Ia, Ib, and IIb; endoglucanases II and V; beta-glucosidase, xylanase II), artificial multienzyme mixtures were reconstituted, displaying an extremely high performance in a conversion of different cellulosic substrates (Avicel, cotton, pretreated Douglas fir wood) to glucose. These mixtures were much or notably more effective in hydrolysis of the cellulosic substrates than the crude multienzyme C. lucknowense preparation and other crude cellulase samples produced by T. reesei and Penicillium verruculosum. Highly active cellulases are a key factor in bioconversion of plant lignocellulosic biomass to ethanol as an alternative to fossil fuels.
The sorting sequence of the peroxisomal integral membrane protein PMP47 is contained within a short hydrophilic loop. (1996)

No targeting sequence for peroxisomal integral membrane proteins has yet been identified. We have previously shown that a region of 67 amino acids is necessary to target Pmp47, a protein that spans the membrane six times, to peroxisomes. This region comprises two membrane spans and the intervening loop. We now demonstrate that the 20 amino acid loop, which is predicted to face the matrix, is both necessary and sufficient for peroxisomal targeting. Sufficiency was demonstrated with both chloramphenicol acetyltransferase and green fluorescent protein as carriers. There is a cluster of basic amino acids in the middle of the loop that we predict protrudes from the membrane surface into the matrix by a flanking stem structure. We show that the targeting signal is composed of this basic cluster and a block of amino acids immediately down-stream from it.
Pyrroles and related compounds. Part XXVI. Pyrrole β-keto-esters (1974)

Various attempts to synthesise β-keto-esters of pyrroles for use as model compounds, or as intermediates in chlorophyll synthesis, are described. Carboxylation of acetylpyrroles, using dialkyl carbonates or chloroformates, gave a variety of products, including a β-keto-ester and (unexpectedly)N-alkyl- as well as N-alkoxycarbonyl-pyrroles. Attempts to utilise pyrrylacetylenes were unsuccessful, as were direct acylation reactions with derivatives of malonic ester. The most successful approach involved the coupling of a pyrryl acid chloride with the sodium salts of monoalkyl monobenzyl (or mono-t-butyl) esters of malonic acid; the β-keto-diester thus obtained could then be converted (by hydrogenolysis or treatment with cold trifluoroacetic acid) into the desired β-keto-ester.
A cladistic analysis of phenotypic associations with haplotypes inferred from restriction endonuclease mapping and DNA sequence data. III. Cladogram estimation. (1992)

We previously developed a cladistic approach to identify subsets of haplotypes defined by restriction endonuclease mapping or DNA sequencing that are associated with significant phenotypic deviations. Our approach was limited to segments of DNA in which little recombination occurs. In such cases, a cladogram can be constructed from the restriction site or sequence data that represents the evolutionary steps that interrelate the observed haplotypes. The cladogram is used to define a nested statistical design to identify mutational steps associated with significant phenotypic deviations. The central assumption behind this strategy is that any undetected mutation causing a phenotypic effect is embedded within the same evolutionary history that is represented by the cladogram. The power of this approach depends upon the confidence one has in the particular cladogram used to draw inferences. In this paper, we present a strategy for estimating the set of cladograms that are consistent with a particular sample of either restriction site or nucleotide sequence data and that includes the possibility of recombination. We first evaluate the limits of parsimony in constructing cladograms. Once these limits have been determined, we construct the set of parsimonious and nonparsimonious cladograms that is consistent with these limits. Our estimation procedure also identifies haplotypes that are candidates for being products of recombination. If recombination is extensive, our algorithm subdivides the DNA region into two or more subsections, each having little or no internal recombination. We apply this estimation procedure to three data sets to illustrate varying degrees of cladogram ambiguity and recombination.
Computerized extraction of coded findings from free-text radiologic reports. Work in progress. (1990)

A computerized data acquisition tool, the special purpose radiology understanding system (SPRUS), has been implemented as a module in the Health Evaluation through Logical Processing Hospital Information System. This tool uses semantic information from a diagnostic expert system to parse free-text radiology reports and to extract and encode both the findings and the radiologists' interpretations. These coded findings and interpretations are then stored in a clinical data base. The system recognizes both radiologic findings and diagnostic interpretations. Initial tests showed a true-positive rate of 87% for radiographic findings and a bad data rate of 5%. Diagnostic interpretations are recognized at a rate of 95% with a bad data rate of 6%. Testing suggests that these rates can be improved through enhancements to the system's thesaurus and the computerized medical knowledge that drives it. This system holds promise as a tool to obtain coded radiologic data for research, medical audit, and patient care.
Characterization of an Endoglucanase from Pseudomonas fluorescens subsp. cellulosa Produced in Escherichia coli and Regulation of the Expression of Its Cloned Gene (1988)

Several enzymatic properties of an endoglucanase produced in Escherichia coli by a gene from Pseudomonas fluorescens subsp. cellulosa were investigated. Gel filtration revealed a single peak of M(r) 36,000 with endoglucanase activity. The pH optimum of the enzyme was 7.0. Carboxymethyl cellulose and barley beta-glucan (mixed beta-1,3 and 1,4 linkages) were good substrates, but not laminarin (beta-1,3 linkages), amylose, filter paper, microcrystalline cellulose (Avicel), or cellotriose. The mode of action was typical of an "endo"-acting enzyme. Taken together, these properties do not correspond to those of any of the endoglucanases described in P. fluorescens subsp. cellulosa. Consequently, the gene was designated egIX. The enzyme was sensitive to end-product inhibition by cellobiose but was only moderately inhibited by glucose. The enzyme was formed constitutively in E. coli throughout the growth phase. Urea had no effect on endoglucanase synthesis, but glucose acted as a catabolite repressor. The formation of the enzyme in E. coli was partially dependent on cyclic AMP.
Identification of the minimal region in lipase ABC transporter recognition domain of Pseudomonas fluorescens for secretion and fluorescence of green fluorescent protein (2012)

LARD3 was a potent secretion signal in T1SS for its fusion flanking RTX motif, which enhanced secretion and preserved the fluorescence of GFP. LARD3-mediated secretion in E. coli or P. fluorescens will enable the development of enhanced protein manufacturing factory and recombinant microbe secreting protein of interest in situ.
Insights into the reversible oxygen reduction reaction in a series of phosphonium-based ionic liquids (2014)

New findings supporting the stability of the superoxide ion, O2˙(-), in the presence of the phosphonium cation, [P6,6,6,14](+), are presented. Extended electrochemical investigations of a series of neat phosphonium-based ILs with different anions, including chloride, bis(trifluoromethylsulfonyl)imide and dicyanamide, demonstrate the chemical reversibility of the oxygen reduction process. Quantum chemistry calculations show a short intermolecular distance (r = 3.128 Å) between the superoxide ion and the phosphonium cation. NMR experiments have been performed to assess the degree of long term degradation of [P6,6,6,14](+), in the presence of superoxide and peroxide species, showing no chemically distinct degradation products of importance in reversible air cathodes.
Binding of a soluble alpha beta T-cell receptor to superantigen/major histocompatibility complex ligands. (1994)

The genes for the alpha and beta chains of a murine T-cell receptor were truncated just prior to the portions encoding the transmembrane regions and introduced into baculovirus by recombination. Insect cells infected with the virus secreted a soluble form of the receptor that could be purified to homogeneity. This soluble receptor reacted with a set of six monoclonal antibodies originally raised to different epitopes on the natural transmembrane-region-containing receptor and bound with appropriate specificity to a cell surface complex of the human major histocompatibility complex class II molecule DR1 with the bacterial superantigen staphylococcal enterotoxin B.
Fragmentation of a highly purified monoclonal antibody attributed to residual CHO cell protease activity (2010)

Monoclonal antibody (mAb) fragmentation can be a widespread problem across the biotechnology industry and there is a current need to better understand the underlying principles. Here, we report an example of a high-purity human IgG1 mAb prepared from CHO cells exhibiting fragmentation that can be attributed to residual proteolytic enzyme activity. The concomitant occurrence of proteolytic and non-proteolytic peptide bond cleavage is shown and the respective fragmentation patterns characterized using high-resolution LC-MS. Fragmentation rates are monitored by SE-HPLC and SDS-PAGE over the pH range 4-6 and characterized in the presence and absence of pepstatin A, an inhibitor of acidic proteases. After 20 days at 40°C, pH 4, ∼60% decrease in BIIB-mAb monomer peak occurred attributed to residual proteolytic activity. At pH 5, this value was ∼13%. These results have implications for formulation design studies and the interpretation of accelerated stability data. A simple method to screen for acidic protease activity using the proteolytic enzyme inhibitor pepstatin A is described.
Signal-to-noise ratio measurement of a 2.5-Gb/s spectrum-sliced incoherent light channel (1997)

We have measured the signal-to-noise ratio (SNR) of a 2.5-Gb/s spectrum-sliced incoherent light channel in the large beat-noise limit. SNR changes strongly in time depending on the receiver electrical filter and the extinction ratio. Except for some minor differences, the SNR behaved quite similar to the theory. In order to obtain a high SNR, the nonreturn-to-zero format should be used rather than the return-to-zero format and the receiver sampling time should be chosen more precisely than that of conventional receivers.
Imidazoquinolines: Recent Developments in Anticancer Activity (2016)

Cancer remains one of the unsolved diseases of today's advanced drug discovery world even though it is known to humans for centuries. There is continued effort to discover new chemotherapeutic agents to improve the outcome of cancer patients. Small-molecule agonists at tolllike receptor 7 and 8 (TLR7/8) have recently generated renewed interest in cancer research owing to their profound antitumoral activity. TLR-7/8 agonist imidazoquinolines (Imiquimod, and Resiquimod) and dual inhibitor of phosphoinositide 3-kinase and mammalian target of rapamycin (NVP-BEZ235) have emerged as clinically important candidates for treating cancers. This article reviews briefly the synthesis, structure-activity relationship (SAR) and biological activities of clinically studied imidazoquinolines along with novel emerging preclinical imidazoquinolines for the anticancer activity.
Novel Aminophenyl Benzamide-Type Histone Deacetylase Inhibitors with Enhanced Potency and Selectivity (2007)

Significant effort is being made to understand the role of HDAC isotypes in human cancer and to develop antitumor agents with better therapeutic windows. A part of this endeavor was the exploration of the 14 A internal cavity adjacent to the enzyme catalytic site, which led to the design and synthesis of compound 4 with the unusual bis(aryl)-type pharmacophore. SAR studies around this lead resulted in optimization to potent, selective, nonhydroxamic acid HDAC inhibitors.
An Introduction to Bioceramics (1993)

Alumina and zirconia, S. Hulbert bioactive glasses - materials science, L. Hench and O. Andersson bioactive glasses-materails science, L. Hench and O. Anderson applications, J. Wilson and R.P. Happonen A/W glass-ceramic - processing and properties, T. Kokubo A/W glass ceramic - clinical applications, T. Yamamuro bioactive glass-ceramics - ceravital, U. Gross et al machineable glass-ceramics, W. Holland and W. Vogel hydroxyapotite, R. LeGros and J. LeGros porous ceramics, R. Holmes and E. Schors resorbable calcium phosphates, C.P.A.T. Klein et al hydroxyapatite coatings, W. Lacefield bioactive glass coatings, L. Hench and O. Andersson pyrolytic carbon coatings, R.H. Dauskardt and R.O. Ritchie bioceramic composites, P. Ducheyne polyethylene-HA composites, W. Bonfield radiotherapy glasses, D. Day characterization of bioceramics, L. Hench regulation of medical devices, E. Horowitz and E. Mueller summary, L. Hench and J. Wilson appendices ASTM standards, J. Lemons and D. Greenspan.
Probing Structure and Dynamics of DNA with 2-Aminopurine:  Effects of Local Environment on Fluorescence (2001)

2-Aminopurine (2AP) is an analogue of adenine that has been utilized widely as a fluorescence probe of protein-induced local conformational changes in DNA. Within a DNA strand, this fluorophore demonstrates characteristic decreases in quantum yield and emission decay lifetime that vary sensitively with base sequence, temperature, and helix conformation but that are accompanied by only small changes in emission wavelength. However, the molecular interactions that give rise to these spectroscopic changes have not been established. To develop a molecular model for interpreting the fluorescence measurements, we have investigated the effects of environmental polarity, hydrogen bonding, and the purine and pyrimidine bases of DNA on the emission energy, quantum yield, and intensity decay kinetics of 2AP in simple model systems. The effects of environmental polarity were examined in a series of solvents of varying dielectric constant, and hydrogen bonding was investigated in binary mixtures of water with 1,4-dioxane or N,N-dimethylformamide (DMF). The effects of the purine and pyrimidine bases were studied by titrating 2AP deoxyriboside (d2AP) with the nucleosides adenosine (rA), cytidine (rC), guanosine (rG), and deoxythymidine (dT), and the nucleoside triphosphates ATP and GTP in neutral aqueous solution. The nucleosides and NTPs each quench the fluorescence of d2AP by a combination of static (affecting only the quantum yield) and dynamic (affecting both the quantum yield and the lifetime, proportionately) mechanisms. The peak wavelength and shape of the emission spectrum are not altered by either of these effects. The static quenching is saturable and has half-maximal effect at approximately 20 mM nucleoside or NTP, consistent with an aromatic stacking interaction. The rate constant for dynamic quenching is near the diffusion limit for collisional interaction (k(q) approximately 2 x 10(9) M(-1) s(-1)). Neither of these effects varies significantly between the various nucleosides and NTPs studied. In contrast, hydrogen bonding with water was observed to have a negligible effect on the emission wavelength, fluorescence quantum yield, or lifetime of 2AP in either dioxane or DMF. In nonpolar solvents, the fluorescence lifetime and quantum yield decrease dramatically, accompanied by significant shifts in the emission spectrum to shorter wavelengths. However, these effects of polarity do not coincide with the observed emission wavelength-independent quenching of 2AP fluorescence in DNA. Therefore, we conclude that the fluorescence quenching of 2AP in DNA arises from base stacking and collisions with neighboring bases only but is insensitive to base-pairing or other hydrogen bonding interactions. These results implicate both structural and dynamic properties of DNA in quenching of 2AP and constitute a simple model within which the fluorescence changes induced by protein-DNA binding or other perturbations may be interpreted.