gebhart/patrepeval huggingface dataset:
Unnatural Substrate Repertoire of A, B, and X Family DNA Polymerases (2008)

As part of an effort to develop unnatural base pairs that are stable and replicable in DNA, we examined the ability of five different polymerases to replicate DNA containing four different unnatural nucleotides bearing predominantly hydrophobic nucleobase analogs. The unnatural pairs were developed based on intensive studies using the Klenow fragment of DNA polymerase I from E. coli (Kf) and found to be recognized to varying degrees. The five additional polymerases characterized here include family A polymerases from bacteriophage T7 and Thermus aquaticus, family B polymerases from Thermococcus litoralis and Thermococcus 9(o)N-7, and the family X polymerase, human polymerase beta. While we find that some aspects of unnatural base pair recognition are conserved among the polymerases, for example, the pair formed between two d3FB nucleotides is typically well recognized, the detailed recognition of most of the unnatural base pairs is generally polymerase dependent. In contrast, we find that the pair formed between d5SICS and dMMO2 is generally well recognized by all of the polymerases examined, suggesting that the determinants of efficient and general recognition are contained within the geometric and electronic structure of these unnatural nucleobases themselves. The data suggest that while the d3FB:d3FB pair is sufficiently well recognized by several of the polymerases for in vitro applications, the d5SICS:dMMO2 heteropair is likely uniquely promising for in vivo use. T7-mediated replication is especially noteworthy due to strong mispair discrimination.
Vizard II, a PCI-card for real-time volume rendering (1998)

No abstract available.
Ferroelectric Polymers (1983)

Piezoelectricity and pyroelectricity, traditionally encountered in certain single crystals and ceramics, have now also been documented in a number of polymers. Recently, one such polymer-poly(vinylidene fluoride)-and some of its copolymers have been shown to be ferroelectric as well. The extraordinary molecular and supermolecular structural requirements for ferroelectric behavior in polymers are discussed in detail, with particular emphasis on poly(vinylidene fluoride). Piezoelectric, pyroelectric, and ferroelectric properties are also briefly reviewed, as are some promising applications of such polymers.
The Use of Polyphosphoric Acid in the Synthesis of 2-Aryl- and 2-Alkyl-substituted Benzimidazoles, Benzoxazoles and Benzothiazoles1 (1957)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Use of Polyphosphoric Acid in the Synthesis of 2-Aryl- and 2-Alkyl-substituted Benzimidazoles, Benzoxazoles and Benzothiazoles1D. W. Hein, R. J. Alheim, and J. J. LeavittCite this: J. Am. Chem. Soc. 1957, 79, 2, 427–429Publication Date (Print):January 1, 1957Publication History Published online1 May 2002Published inissue 1 January 1957https://pubs.acs.org/doi/10.1021/ja01559a053https://doi.org/10.1021/ja01559a053research-articleACS PublicationsRequest reuse permissionsArticle Views4398Altmetric-Citations432LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Analysis of androgenic steroid Girard P hydrazones using multistage tandem mass spectrometry (2006)

Seven androgenic steroids have been converted into steroid hydrazones using Girard P hydrazine and analysed by electrospray ionisation multistage tandem mass spectrometry. The cationic derivatives 17alpha-testosterone hydrazone, 17beta-nortestosterone hydrazone, 17beta-bolasterone hydrazone, 17alpha-boldenone hydrazone, 17beta-fluoxymesterone hydrazone, 17alpha-trenbolone hydrazone and 4-chloroandrosten-3,17-dione hydrazone show good response in positive ion mode with enhancements for the method of up to 33 times relative to the native species. Detailed characterisation of fragmentation pathways reveals structurally specific ions formed by fragmentation of the hydrazine moiety. Comparison of structural similarities among the androgenic steroids allows recognition of common ions/fragmentation processes as well as analyte-specific transitions. The suitability of the derivatisation approach in the screening of heifer urine for the presence of administered hormones has been demonstrated using partially purified urine spiked with a mixture of androgenic steroids.
Controlled Folding of Micrometer-Size Structures (1995)

Several types of microactuators have been fabricated, from simple paddles to self-assembling and -disassembling cubes. Conducting bilayers made of a layer of polymer and a layer of gold were used as hinges to connect rigid plates to each other and to a silicon substrate. The bending of the hinges was electrically controlled and reversible, allowing precise three-dimensional positioning of the plates. The structures were released from the substrate with a technique based on differential adhesion. This method, which avoids the use of a sacrificial layer and allows the actuators to pull themselves off the surface, may have general applications in micromachining. Possibilities include the manufacture, of surfaces whose light reflection or chemical properties can be switched.
Quantification of mRNA for the vitamin D metabolizing enzymes CYP27B1 and CYP24 and vitamin D receptor in kidney using real-time reverse transcriptase- polymerase chain reaction (2003)

Critical to an understanding of the control of 1,25-dihydroxyvitamin D (1,25D) activity is a molecular appreciation of the regulation of three genes, 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1), 25-hydroxyvitamin D-24-hydroxylase (CYP24) and vitamin D receptor (VDR). We now report the sensitivity, reproducibility and accuracy of a real-time reverse transcriptase-polymerase chain reaction protocol (Taqman) for the quantification of mRNA levels for these genes in total RNA extracted from kidney tIssue. The sensitivity of the protocol was at least 150 copies of mRNA per reaction. Reproducibility, expressed as the coefficient of variation, ranged between 14 and 30% at the level of approximately 10(4) copies of mRNA per reaction. Accuracy was estimated at greater than 95% for each of these mRNAs. This protocol allows for the comparison of absolute mRNA levels in extracted total RNA in kidneys from animals fed diets containing different levels of calcium, ranging from 0.05% to 1%. Serum 1,25D levels were decreased when the dietary calcium concentration was increased (P<0.05). The levels of CYP27B1 mRNA were highest in the animals fed the 0.05% calcium diet (P<0.01). Conversely, CYP24 and VDR mRNA levels were highest in the animals fed the 1% calcium diet (P<0.01). Both CYP27B1 and CYP24 mRNA levels were major determinants of serum 1,25D levels when dietary calcium intakes were varied in these adult animals (Multiple R(2)=0.70, P<0.01). No significant relationship was detected between kidney CYP27B1 and serum parathyroid hormone (PTH) suggesting that serum calcium may regulate CYP27B1 mRNA expression directly during normocalcaemia. Low levels of CYP24 mRNA were associated with high PTH levels. These findings suggest that kidney CYP24 activity, possibly regulated by factors such as PTH, acts in concert with kidney CYP27B1 to control serum 1,25D levels.
Benzoquinone-Promoted Reaction of O2 with a PdII−Hydride (2011)

Benzoquinone (BQ) and O(2) are among the most common stoichiometric oxidants in Pd-catalyzed oxidation reactions. The present study provides rare insights into mechanistic differences between BQ and O(2) in their reactivity with a well-defined Pd-hydride complex, Pd(IMes)(2)(H)(O(2)CPh) (1). BQ promotes the reductive elimination of PhCO(2)H from 1 and catalyzes the formation of a Pd(II)-OOH complex when this reaction is carried out under aerobic conditions. These results have important implications for Pd-catalyzed oxidation reactions.
Comparing potential early caries assessment methods for teledentistry (2013)

Although MID and CP-OCT were useful in detecting the presence of demineralization, examiners were not able to utilize these devices to adequately assess the depth of the demineralization. This study found that MID and CP-OCT did not have markedly superior diagnostic values from simple CAM assessment for use in teledentistry.
Biological Activity of Some Oxygenated Sterols (1978)

A group of oxygenated sterols has been identified as potent and specific inhibitors of sterol biosynthesis. The ability of these compounds to inhibit sterol synthesis in cultured cells and the ineffectiveness of cholesterol under the same conditions suggest that feedback regulation of sterol biosynthesis may be brought about by an oxygenated sterol rather than by cholesterol. The nature of the regulatory sterol may vary in different cells with their specific requirements for cholesterol as a structural component or as a precursor of other steroid products. The use of oxygenated sterols to block sterol synthesis in cultured cells provides new information regarding the role of sterol in cell membrane structure and function. For example, de novo sterol synthesis is required for DNA synthesis and cell division by some cultured cells. Studies with cultured cells, and with rats and mice in vivo, suggest that oxygenated sterols could be of value in the treatment of several important human diseases.
Peptide hormone exendin‐4 stimulates subventricular zone neurogenesis in the adult rodent brain and induces recovery in an animal model of parkinson's disease (2007)

We investigated the effects of exendin-4 on neural stem/progenitor cells in the subventricular zone of the adult rodent brain and its functional effects in an animal model of Parkinson's disease. Our results showed expression of GLP-1 receptor mRNA or protein in the subventricular zone and cultured neural stem/progenitor cells isolated from this region. In vitro, exendin-4 increased the number of neural stem/progenitor cells, and the number of cells expressing the neuronal markers microtubule-associated protein 2, beta-III-tubulin, and neuron-specific enolase. When exendin-4 was given intraperitoneally to naïve rodents together with bromodeoxyuridine, a marker for DNA synthesis, both the number of bromodeoxyuridine-positive cells and the number of neuronal precursor cells expressing doublecortin were increased. Exendin-4 was tested in the 6-hydroxydopamine model of Parkinson's disease to investigate its possible functional effects in an animal model with neuronal loss. After unilateral lesion and a 5-week stabilization period, the rats were treated for 3 weeks with exendin-4. We found a reduction of amphetamine-induced rotations in animals receiving exendin-4 that persisted for several weeks after drug administration had been terminated. Histological analysis showed that exendin-4 significantly increased the number of both tyrosine hydroxylase- and vesicular monoamine transporter 2-positive neurons in the substantia nigra. In conclusion, our results show that exendin-4 is able to promote adult neurogenesis in vitro and in vivo, normalize dopamine imbalance, and increase the number of cells positive for markers of dopaminergic neurons in the substantia nigra in a model of Parkinson's disease.
PCR-Induced Sequence Artifacts and Bias: Insights from Comparison of Two 16S rRNA Clone Libraries Constructed from the Same Sample (2005)

The contribution of PCR artifacts to 16S rRNA gene sequence diversity from a complex bacterioplankton sample was estimated. Taq DNA polymerase errors were found to be the dominant sequence artifact but could be constrained by clustering the sequences into 99% sequence similarity groups. Other artifacts (chimeras and heteroduplex molecules) were significantly reduced by employing modified amplification protocols. Surprisingly, no skew in sequence types was detected in the two libraries constructed from PCR products amplified for different numbers of cycles. Recommendations for modification of amplification protocols and for reporting diversity estimates at 99% sequence similarity as a standard are given.
Two Routes of Metabolic Cross-Feeding betweenBifidobacterium adolescentisand Butyrate-Producing Anaerobes from the Human Gut (2006)

Dietary carbohydrates have the potential to influence diverse functional groups of bacteria within the human large intestine. Of 12 Bifidobacterium strains of human gut origin from seven species tested, four grew in pure culture on starch and nine on fructo-oligosaccharides. The potential for metabolic cross-feeding between Bifidobacterium adolescentis and lactate-utilizing, butyrate-producing Firmicute bacteria related to Eubacterium hallii and Anaerostipes caccae was investigated in vitro. E. hallii L2-7 and A. caccae L1-92 failed to grow on starch in pure culture, but in coculture with B. adolescentis L2-32 butyrate was formed, indicating cross-feeding of metabolites to the lactate utilizers. Studies with [(13)C]lactate confirmed carbon flow from lactate, via acetyl coenzyme A, to butyrate both in pure cultures of E. hallii and in cocultures with B. adolescentis. Similar results were obtained in cocultures involving B. adolescentis DSM 20083 with fructo-oligosaccharides as the substrate. Butyrate formation was also stimulated, however, in cocultures of B. adolescentis L2-32 grown on starch or fructo-oligosaccharides with Roseburia sp. strain A2-183, which produces butyrate but does not utilize lactate. This is probably a consequence of the release by B. adolescentis of oligosaccharides that are available to Roseburia sp. strain A2-183. We conclude that two distinct mechanisms of metabolic cross-feeding between B. adolescentis and butyrate-forming bacteria may operate in gut ecosystems, one due to consumption of fermentation end products (lactate and acetate) and the other due to cross-feeding of partial breakdown products from complex substrates.
P-loop Conformation Governed Crizotinib Resistance in G2032R-Mutated ROS1 Tyrosine Kinase: Clues from Free Energy Landscape (2014)

Tyrosine kinases are regarded as excellent targets for chemical drug therapy of carcinomas. However, under strong purifying selection, drug resistance usually occurs in the cancer cells within a short term. Many cases of drug resistance have been found to be associated with secondary mutations in drug target, which lead to the attenuated drug-target interactions. For example, recently, an acquired secondary mutation, G2032R, has been detected in the drug target, ROS1 tyrosine kinase, from a crizotinib-resistant patient, who responded poorly to crizotinib within a very short therapeutic term. It was supposed that the mutation was located at the solvent front and might hinder the drug binding. However, a different fact could be uncovered by the simulations reported in this study. Here, free energy surfaces were characterized by the drug-target distance and the phosphate-binding loop (P-loop) conformational change of the crizotinib-ROS1 complex through advanced molecular dynamics techniques, and it was revealed that the more rigid P-loop region in the G2032R-mutated ROS1 was primarily responsible for the crizotinib resistance, which on one hand, impaired the binding of crizotinib directly, and on the other hand, shortened the residence time induced by the flattened free energy surface. Therefore, both of the binding affinity and the drug residence time should be emphasized in rational drug design to overcome the kinase resistance.
Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer (2015)

Among patients with advanced, previously treated squamous-cell NSCLC, overall survival, response rate, and progression-free survival were significantly better with nivolumab than with docetaxel, regardless of PD-L1 expression level. (Funded by Bristol-Myers Squibb; CheckMate 017 ClinicalTrials.gov number, NCT01642004.).
The impact of architectural trends on operating system performance (1995)

Computer systems are rapidly changing. Over the next few years, we will see wide-scale deployment of dynamically-scheduled processors that can issue multiple instructions every clock cycle, execute instructions out of order, and overlap computation and cache misses. We also expect clock-rates to increase, caches to grow, and multiprocessors to replace uniprocessors. Using SimOS, a complete machine simulation environment, this paper explores the impact of the above architectural trends on operating system performance. We present results based on the execution of large and realistic workloads (program development, transaction processing, and engineering compute-server) running on the IRIX 5.3 operating system from Silicon Graphics Inc.
Structural and Catalytic Properties of the Four Phenylalanine Ammonia‐Lyase Isoenzymes from Parsley (Petroselinum Crispum Nym.) (1994)

Near-full-length cDNAs for the four phenylalanine ammonia-lyase (PAL) isoenzymes in parsley (Petroselium crispum Nym.) were cloned and the complete amino acid sequences deduced. Fusion proteins with glutathione S-transferase were expressed in Escherichia coli, purified and cleaved. All of the resulting phenylalanine ammonia-lyase proteins, as well as the fusion proteins, were catalytically active. The turnover number of one selected isoenzyme, PAL-1, was estimated to be around 22 s-1 for each active site. In contrast to a certain degree of differential expression in various parts of parsley plants, the four phenylalanine ammonia-lyase isoenzymes exhibited very similar apparent Km values for L-phenylalanine (15-24.5 microM) as well as identical temperature (58 degrees C) and pH (8.5) optima. All of them were competitively inhibited by (E)-cinnamate with similar efficiency (Ki values: 9.1-21.5 microM), lacked cooperative behaviour, and accepted L-tyrosine as a substrate with low affinity (Km values: 2.6-7.8 mM). These results suggest that the occurrence of multiple gene copies has a function other than encoding isoenzymes with different enzyme kinetic properties.
Topical Triiodothyronine Stimulates Epidermal Proliferation, Dermal Thickening, and Hair Growth in Mice and Rats (2001)

The skin is a classic target tissue for thyroid hormone action. Although the histology of skin in hypothyroid states is well documented, the literature contains little assessment of skin in thyrotoxic states. In light of the paucity of information on skin under the influence of excess thyroid hormone, we investigated the direct effect of thyroid hormone on skin. Triiodothyronine (T3) was applied topically daily in liposomes to SKH-1 hairless mice for 7 days and to CD rats for 2 weeks. There was a dose-dependent increase in epidermal proliferation, dermal thickening, and hair growth in T3-treated animals. Mice that received 3.8 microg of T3 had 42% more hairs per millimeter than controls (p < 0.01), hair length that was 1,180% longer (p < 0.001), 49% greater epidermal 3H-thymidine incorporation (p < 0.01), and 80% more 5-bromo-2'-deoxyuridine (BrdU) stained cells (p < 0.05). Rats receiving 12.8 microg T3 had 48% greater dermal thickness than controls (p < 0.001), 26% greater epidermal thickness (p < 0.001), 85% more hairs per millimeter (p < 0.005), and 130% greater 3H-thymidine incorporation into the epidermis (p < 0.01). Thus, topically applied thyroid hormone has dramatic effects on both skin and hair growth. These observations offer a new strategy for developing thyroid hormone and its analogues for treating disorders of skin and hair growth.
Herpes Simplex Virus Types 1 and 2 Completely Help Adenovirus-Associated Virus Replication (1981)

In addition to adenoviruses, which are capable of completely helping adenovirus-associated virus (AAV) multiplication, only herpesviruses are known to provide any AAV helper activity, but this activity has been thought to be partial (i.e., AAV DNA, RNA, and protein syntheses are induced, but infectious particles are not assembled). In this study, however, we show that herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are in fact complete AAV helpers and that AAV type 2 (AAV2) infectivity yields can approach those obtained when coinfections are carried out with a helper adenovirus. AAV helper activity was demonstrated in KB cells with two HSV-1 strains (11124 and 17MP) and an HSV-2 strain (HG52). Each herpesvirus supported AAV2 multiplication with comparable efficiency. AAV2 multiplication was similarly efficient in HSV-1 coinfections of HeLa cells, whereas lower yields were obtained in HEp-2 and primary human embryonic kidney cells. HSV-1 also supported AAV1 multiplication in HeLa cells but, at corresponding multiplicities of infection, AAV1 grew less efficiently than AAV2. Comparisons of the time courses of AAV2 DNA, RNA, and protein syntheses after coinfection with either adenovirus type 5 or HSV-1 revealed that, in each case, the onset of synthesis and attainment of maximal synthesis rate occurred earlier in coinfections with HSV-1. These findings demonstrate the linkage of AAV macromolecular synthesis to an event(s) in the helper virus cycle. Aside from this temporal association, helper-related differences in AAV macromolecular synthesis were not apparent.
A role for uncoupling protein‐2 as a regulator of mitochondrial hydrogen peroxide generation (1997)

According to the state of mitochondrial respiration, the respiratory chain generates superoxide anions converted into hydrogen peroxide. Two uncoupling proteins (UCP) able to modulate the coupling between the respiratory chain and ATP synthesis are now identified and could be involved in mitochondrial H2O2 generation. UCP1 is specific to brown adipose tissue (BAT) whereas UCP2 is expressed in numerous tissues, particularly in monocytes/macrophages. Preincubation of BAT mitochondrial fractions with GDP, an inhibitor of UCP1, induced a rise in mitochondrial membrane potential (assessed by rhodamine 123 uptake) and H2O2 production. An uncoupling agent reversed this effect. Liver mitochondria exhibited a similar phenotype. GDP was also able to raise membrane potential and H2O2 production of the mitochondria from nonparenchymal cells expressing UCP2, but was completely ineffective on mitochondria from hepatocytes deprived of UCP2. The GDP effect was also observed with mitochondrial fractions of the spleen or thymus, which highly expressed UCP2. Altogether, these results strongly suggest that UCP2 is sensitive to GDP and that the UCPs, particularly UCP2, are able to modulate H2O2 mitochondrial generation. This supports a role for UCP2 in cellular (patho-) physiological processes involving free radicals generated by mitochondria, such as oxidative damage, inflammation, or apoptosis.