gebhart/patrepeval huggingface dataset:
Comparative Study of Modification of DNA and RNA by Oligo(2′-O-Methylribonucleotide) Derivatives (1998)

Abstract The results of modification of the model DNA and RNA targets by the alkylating derivatives of 2′-O-methylribo-, ribo-, and deoxyhexanucleotides in the presence and absence of effectors (N-(2-hydroxyethyl)phenazinium derivatives of the same type of octanucleotides) are presented. It has been shown that the alkylating 4(N-methyl-N-2-chloroethyl-)benzylmethylamidophosphate derivatives of oligo(2′-O-methylribonucleotides) are the high effective reagents for the site specific modification of nucleic acids especially RNA.
XXVI.—Nitro-, arylazo-, and amino-glyoxalines (1919)

R. G. Fargher and F. L. Pyman, J. Chem. Soc., Trans., 1919, 115, 217 DOI: 10.1039/CT9191500217
Global Coordination of Local Linear Models (2001)

High dimensional data that lies on or near a low dimensional manifold can be described by a collection of local linear models. Such a description, however, does not provide a global parameterization of the manifold---arguably an important goal of unsupervised learning. In this paper, we show how to learn a collection of local linear models that solves this more difficult problem. Our local linear models are represented by a mixture of factor analyzers, and the &amp;quot;global coordination&amp;quot; of these models is achieved by adding a regularizing term to their objective function. The regularizer breaks a degeneracy in the mixture model&amp;apos;s parameter space, favoring models whose internal coordinate systems are aligned in a consistent way. As a result, the internal coordinates change smoothly and continuously as one traverses a connected path on the manifold---even when the path crosses the domains of many different local models. The regularizer takes the form of a Kullback-Leibler divergerence and illustrates an unexpected application of variational methods: not to perform approximate inference in intractable probabilistic models, but to learn more useful internal representations in tractable ones.
The Structure of a Mutant Photosynthetic Reaction Center Shows Unexpected Changes in Main Chain Orientations and Quinone Position (2002)

We report on the unexpected structural changes caused by substitution of acidic amino acids in the Q(B) binding pocket of the bacterial photosynthetic reaction center by alanines. The mutations targeted key residues L212Glu and L213Asp of this transmembrane protein-cofactor complex. The amino acid substitutions in the L212Ala-L213Ala mutant reaction center ("AA") were known to affect the delivery of protons after the light-induced generation of Q(B)(-), which renders the AA strain incapable of photosynthetic growth. The AA structure not only revealed side chain rearrangements but also showed movement of the main chain segments that are contiguous with the mutation sites. The alanine substitutions caused an expansion of the cavity rather than its collapse. In addition, Q(B) is found mainly in the binding site that is proximal to the iron-ligand complex (closest to Q(A)) as opposed to its distal binding site (furthest from Q(A)) in the structure of the wild-type reaction center. The observed rearrangements in the structure of the AA reaction center establish a new balance between charged residues of an interactive network near Q(B). This structurally and electrostatically altered complex forms the basis for future understanding of the structural basis for proton transfer in active reaction centers which retain the alanine substitutions but carry a distant compensatory mutation.
Characterization of a Novel Cutaneous Human Papillomavirus Genotype HPV-125 (2011)

The DNA genome of a novel HPV genotype, HPV-125, isolated from a hand wart of an immuno-competent 19-year old male was fully cloned, sequenced and characterized. The full genome of HPV-125 is 7,809-bp in length with a GC content of 46.4%. By comparing the nucleotide sequence of the complete L1 gene, HPV-125 is phylogenetically placed within cutaneotrophic species 2 of Alphapapillomaviruses, and is most closely related to HPV-3 and HPV-28. HPV-125 has a typical genomic organization of Alphapapillomaviruses and contains genes coding for five early proteins, E6, E7, E1, E2 and E4 and two late capsid proteins, L1 and L2. The genome contains two non-coding regions: the first located between the L1 and E6 genes (nucleotide positions 7,137-7,809, length 673-bp) and the second between genes E2 and L2 (nucleotide positions 3,757-4,216, length 460-bp). The E6 protein of HPV-125 contains two regular zinc-binding domains at amino acid positions 29 and 102, whereas the E7 protein exhibits one such domain at position 50. HPV-125 lacks the regular pRb-binding core sequence within its E7 protein. In order to assess the tissue predilection and clinical significance of HPV-125, a quantitative type-specific real-time PCR was developed. The 95% limit-of-detection of the assay was 2.5 copies per reaction (range 1.7-5.7) and the intra- and inter-assay coefficients of variation were 0.47 and 2.00 for 100 copies per reaction, and 1.15 and 2.15 for 10 copies per reaction, respectively. Testing of a representative collection of HPV-associated mucosal and cutaneous benign and malignant neoplasms and hair follicles (a total of 601 samples) showed that HPV-125 is a relatively rare HPV genotype, with cutaneous tropism etiologically linked with sporadic cases of common warts.
A Mass Spectrometric Approach for the Study of the Metabolism of Clomiphene, Tamoxifen and Toremifene by Liquid Chromatography Time-of-Flight Spectroscopy (2008)

In this paper, we discuss the capabilities of liquid chromatography coupled to mass spectrometry with a time-of flight system with accurate mass measurement for the detection and characterisation of drug metabolites in biological samples for anti-doping purpose. Urinary excretion samples of three selective oestrogen receptor modulators (SERMs) with a common triphenylethylene structure: clomiphene, toremifene, and tamoxifen, obtained after oral administration of a single dose of each drug, were analysed using a time-of-flight system, after automatic tuning and calibration of the equipment, in positive full scan mode using an electrospray ionisation source. Following this approach we detected most of all significant metabolites reported by others and postulated new metabolites, especially for toremifene, have been characterised: N-demethyl-3-hydroxy-4-methoxy-toremifene and 3- hydroxy-4-methoxy-toremifene; in addtiona to this, in the urinary excretion samples of toremifene some metabolites, without the characteristic chlorine isotope pattern, discarded in previous studies, that are also metabolites of tamoxifen, were identified. The lack of certified reference materials does not allow an accurate determination of the limit of detection (LODs) of all metabolites; however an estimation taking into account the response factor of similar compounds allows to estimate that all metabolites are clearly detectable in a range of concentration comprised between 10 ng mL(-1) and 30 ng mL(-1).
Life strategies of Bryophytes: a preliminary review (1979)

An attempt is made to compare bryophyte Ufe histories with recent models of life strategies of animals and phanerogams. Important life history traits in bryophytes include the balance between sexual and asexual reproduction, the reproductive effort spent on both kinds of reproduction, the size and number of the spores, and annual production and standing crop. Age of first reproduction is generally low for asexual reproduction, but low or high for sexual reproduction, depending on the species and the population included. Density-dependent mortality appears to be rare in bryophytes; in some groups of species mortality is for the greater part caused by abiotic environmental stress, whereas in other groups biotic factors such as competi tion and pr?dation are more prominent. Life expectancy varies from some weeks in extreme ephemerals to hundreds of years; in the longer lived species wide variation in life span of different individuals occurs. Tolerance and avoidance of environmental stress are two distinct alternative possibilities in bryophytes as well as in phanerogams. A preliminary system of six different bryophyte life strategies is pre sented. It is stressed that the choice of a fitness measure for a species or population should be made in accordance to its life strategy. Finally, some distinctive traits of bryophyte life histories are outlined.
Is a Closing “GA Pair” a Rule for Stable Loop-Loop RNA Complexes? (2000)

RNA hairpin aptamers specific for the trans-activation-responsive (TAR) RNA element of human immunodeficiency virus type 1 were identified by in vitro selection (Ducongé, F., and Toulmé, J. J. (1999) RNA 5, 1605-1614). The high affinity sequences selected at physiological magnesium concentration (3 mm) were shown to form a loop-loop complex with the targeted TAR RNA. The stability of this complex depends on the aptamer loop closing "GA pair" as characterized by preliminary electrophoretic mobility shift assays. Thermal denaturation monitored by UV-absorption spectroscopy and binding kinetics determined by surface plasmon resonance show that the GA pair is crucial for the formation of the TAR-RNA aptamer complex. Both thermal denaturation and surface plasmon resonance experiments show that any other "pairs" leads to complexes whose stability decreases in the order AG > GG > GU > AA > GC > UA >> CA, CU. The binding kinetics indicate that stability is controlled by the off-rate rather than by the on-rate. Comparison with the complex formed with the TAR* hairpin, a rationally designed TAR RNA ligand (Chang, K. Y., and Tinoco, I. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 8705-8709), demonstrates that the GA pair is a key determinant which accounts for the 50-fold increased stability of the TAR-aptamer complex (K(d) = 2.0 nm) over the TAR-TAR* one (K(d) = 92. 5 nm) at physiological concentration of magnesium. Replacement of the wild-type GC pair next to the loop of RNA I' by a GA pair stabilizes the RNA I'-RNA II' loop-loop complex derived from the one involved in the control of the ColE1 plasmid replication. Thus, the GA pair might be the preferred one for stable loop-loop interactions.
Filament Formation of MSF-A, a Mammalian Septin, in Human Mammary Epithelial Cells Depends on Interactions with Microtubules (2003)

Septins are a family of conserved proteins implicated in a variety of cellular functions such as cytokinesis and vesicle trafficking, but their properties and modes of action are largely unknown. Here we now report findings of immunocytochemical and biochemical characterization of a mammalian septin, MSF-A. Using an antibody specific for MSF subfamily proteins, MSF-A was found to be expressed predominantly in mammary human mammary epithelial cells (HMEC). MSF-A was associated with microtubules in interphase HMEC cells as it localized with the mitotic spindle and the bundle of microtubule at midzone during mitosis. Biochemical analysis revealed direct binding of MSF-A with polymerized tubulin through its central region containing guanine nucleotide-interactive motifs. GTPase activity, however, was not required for the association. Conditions that disrupt the microtubule network also disrupted the MSF-A-containing filament structure, resulting in a punctate cytoplasmic pattern. Depletion of MSF-A using small interfering RNAs caused incomplete cell division and resulted in the accumulation of binucleated cells. Unlike Nedd5, an MSF mutant deficient in GTPase activity forms filament indistinguishable from that of the wild type in COS cells. These results strongly suggest that septin filaments may interact not only with actin filaments but also with microtubule networks and that GTPase activity of MSF-A is not indispensable to incorporation of MSF-A into septin filaments.
A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1α regulates the VEGF expression and is potentially involved in lung and vascular development (1997)

We have isolated and characterized a cDNA for a novel Per-Arnt/AhR-Sim basic helix-loop-helix (bHLH-PAS) factor that interacts with the Ah receptor nuclear translocator (Arnt), and its predicted amino acid sequence exhibits significant similarity to the hypoxia-inducible factor 1alpha (HIF1alpha) and Drosophila trachealess (dTrh) gene product. The HIF1alpha-like factor (HLF) encoded by the isolated cDNA bound the hypoxia-response element (HRE) found in enhancers of genes for erythropoietin, vascular endothelial growth factor (VEGF), and various glycolytic enzymes, and activated transcription of a reporter gene harboring the HRE. Although transcription-activating properties of HLF were very similar to those reported for HIF1alpha, their expression patterns were quite different between the two factors; HLF mRNA was most abundantly expressed in lung, followed by heart, liver, and other various organs under normoxic conditions, whereas HIF1alpha mRNA was ubiquitously expressed at much lower levels. In lung development around parturition, HLF mRNA expression was markedly enhanced, whereas that of HIF1alpha mRNA remained apparently unchanged at a much lower level. Moreover, HLF mRNA expression was closely correlated with that of VEGF mRNA. Whole mount in situ hybridization experiments demonstrated that HLF mRNA was expressed in vascular endothelial cells at the middle stages (9.5 and 10.5 days postcoitus) of mouse embryo development, where HIF1alpha mRNA was almost undetectable. The high expression level of HLF mRNA in the O2 delivery system of developing embryos and adult organs suggests that in a normoxic state, HLF regulates gene expression of VEGF, various glycolytic enzymes, and others driven by the HRE sequence, and may be involved in development of blood vessels and the tubular system of lung.
Expression of Mutant BMPR‐II in Pulmonary Endothelial Cells Promotes Apoptosis and a Release of Factors that Stimulate Proliferation of Pulmonary Arterial Smooth Muscle Cells (2011)

Mutations in the bone morphogenetic protein type II receptor gene (BMPR-II) are the major cause of heritable pulmonary arterial hypertension (PAH). Although both endothelial and smooth muscle cell BMPR-II dysfunction have been seen to contribute to pulmonary hypertension in vivo, little is known about the impact of BMPR-II mutation on the interaction between these two important cell types. We employed adenoviral vectors to overexpress wild type or mutant (kinase-deficient mutation, D485G) BMPR-II in human pulmonary arterial endothelial cells (PAECs). PAECs transfected with mutant BMPR-II demonstrated increased susceptibility to apoptosis. Conditioned media from PAECs transfected with mutant BMPR-II increased the proliferation of pulmonary arterial smooth muscle cells (PASMCs), when compared with conditioned media from PAECs transfected with wild-type BMPR-II. PAECs transfected with mutant BMPR-II released higher levels of TGF-β(1) and FGF2 into the conditioned media than the wild-type BMPR-II-transfected cells. Conditioned media from PAECs expressing mutant BMPR-II also showed increased activation of luciferase activity in a TGF-β bioassay. The increased proliferation observed in PASMCs exposed to conditioned media from PAECs expressing mutant BMPR-II was inhibited by neutralizing the antibodies to TGF-β1, or small molecule inhibitors of ALK-5 (SD208) or FGFR1 (SU5402). We conclude that mutation in BMPR-II increases susceptibility to apoptosis of PAECs and leads to secretion of growth factors that stimulate the proliferation of PASMCs. These processes may contribute to the remodeling of pulmonary arteries observed in patients with familial or heritable PAH.
Self-Assembled Water-Soluble Nucleic Acid Probe Tiles for Label-Free RNA Hybridization Assays (2008)

The DNA origami method, in which long, single-stranded DNA segments are folded into shapes by short staple segments, was used to create nucleic acid probe tiles that are molecular analogs of macroscopic DNA chips. One hundred trillion probe tiles were fabricated in one step and bear pairs of 20-nucleotide-long single-stranded DNA segments that act as probe sequences. These tiles can hybridize to their targets in solution and, after adsorption onto mica surfaces, can be examined by atomic force microscopy in order to quantify binding events, because the probe segments greatly increase in stiffness upon hybridization. The nucleic acid probe tiles have been used to study position-dependent hybridization on the nanoscale and have also been used for label-free detection of RNA.
Azinyl and Diazinyl Hydrazones Derived from Aryl N-Heteroaryl Ketones:  Synthesis and Antiproliferative Activity, (1997)

A series of N-heteroaryl hydrazones derived from aryl N-heteroaryl or bis-N-heteroaryl methanones was prepared in search for potential novel antitumor agents. The stereochemistry of these compounds was established by means of NMR spectroscopy. Antiproliferative activity was determined in a panel of human tumor cell lines (CCRF-CEM, Burkitt's lymphoma, HeLa, ZR-75-1, HT-29, and MEXF 276L) in vitro. Generally, the new compounds were found to be more potent (IC50 = 0.011-0.436 microM) than the ribonucleotide reductase inhibitor hydroxyurea (IC50 = 140 microM). Most of the compounds exhibited the highest activity against Burkitt's lymphoma with an IC50 of 0.011-0.035 microM. [14C]Cytidine incorporation into DNA was quantitated for selected hydrazones (Z-A, E-1, Z-3, Z-4, E-5, Z-5, E-13, E-18, Z-19, Z-24, and E-26) as a measure of the inhibition of ribonucleotide reductase in Burkitt's lymphoma cells. The E-configurated compounds were found to inhibit [14C]cytidine incorporation to a greater extent (IC50 = 0.67-5.05 microM) than the Z-isomers (IC50 = 7.20 to > 10 microM). Principal component analysis of the IC50 values obtained for inhibition of cell proliferation revealed that the cell lines tested can be grouped into three main families showing different sensitivities toward the compounds in our series [(i) CCRF-CEM, Burkitt's lymphoma, and Hela; (ii) HT-29; and (iii) MEXF 276 L].
Challenges with Multi-Terminal UHVDC Transmissions (2008)

The paper gives an overview of the operations aspects of parallel operation of HVDC converters, especially in multi-terminal schemes where the converters are located in different locations. For UHVDC schemes, plusmn800 kV or even higher the geographic distances between the stations can be very significant. Considering the high power rating of UHVDC transmissions, the reliability and availability aspects are considered during all stages of development and design. Thus, the consequences of any outage have to be minimized. It is important that faulty equipment is quickly and safely isolated from the remaining transmission system. In a multi-terminal transmission system the telecommunication is important for coordination of current order and maneuvers in the different stations even if there are back-up controls for not losing the power transmission in case of telecommunication failures. The control and protection systems for a multi-terminal UHVDC transmission are conceptually described.
Maximizing the potential of direct aperture optimization through collimator rotation (2007)

Intensity-modulated radiation therapy (IMRT) treatment plans are conventionally produced by the optimization of fluence maps followed by a leaf sequencing step. An alternative to fluence based inverse planning is to optimize directly the leaf positions and field weights of multileaf collimator (MLC) apertures. This approach is typically referred to as direct aperture optimization (DAO). It has been shown that equivalent dose distributions may be generated that have substantially fewer monitor units (MU) and number of apertures compared to fluence based optimization techniques. Here we introduce a DAO technique with rotated apertures that we call rotating aperture optimization (RAO). The advantages of collimator rotation in IMRT have been shown previously and include higher fluence spatial resolution, increased flexibility in the generation of aperture shapes and less interleaf effects. We have tested our RAO algorithm on a complex C-shaped target, seven nasopharynx cancer recurrences, and one multitarget nasopharynx carcinoma patient. A study was performed in order to assess the capabilities of RAO as compared to fixed collimator angle DAO. The accuracy of fixed and rotated collimator aperture delivery was also verified. An analysis of the optimized treatment plans indicates that plans generated with RAO are as good as or better than DAO while maintaining a smaller number of apertures and MU than fluence based IMRT. Delivery verification results show that RAO is less sensitive to tongue and groove effects than DAO. Delivery time is currently increased due to the collimator rotation speed although this is a mechanical limitation that can be eliminated in the future.
A theoretical solution for pile-supported embankments on soft soils under one-dimensional compression (2008)

Pile-supported embankments are increasingly being used for highways, railways, storage tanks, etc. over soft soil because of their effectiveness in accelerating construction and minimizing deformation. The stress transfer mechanisms among all of the components in a piled embankment, including the embankment fill, the piles and (or) caps, and the foundation soils, are complicated. In this study, a closed-form solution for one-dimensional loading was obtained taking into consideration the soil arching in the embankment fill, the negative skin friction along the pile shaft, and the settlement of the foundation soil. In the derivations, the piles, the embankment fill, and the foundation soil were assumed to deform one-dimensionally. This study investigated the stress concentration on top of the pile, the axial load and skin friction distributions along the pile, and the settlement of the embankment. Comparisons demonstrate that the results from this solution are in good agreement with those obtained using a finite element method. It is worth pointing out that this solution should be applied to the piles close to the centerline of the embankment and not to those near the toe of the embankment because of the two-dimensional loading condition near the toe.
Parallel Information Transfer in a Multinode Quantum Information Processor (2012)

We describe a method for coupling disjoint quantum bits (qubits) in different local processing nodes of a distributed node quantum information processor. An effective channel for information transfer between nodes is obtained by moving the system into an interaction frame where all pairs of cross-node qubits are effectively coupled via an exchange interaction between actuator elements of each node. All control is achieved via actuator-only modulation, leading to fast implementations of a universal set of internode quantum gates. The method is expected to be nearly independent of actuator decoherence and may be made insensitive to experimental variations of system parameters by appropriate design of control sequences. We show, in particular, how the induced cross-node coupling channel may be used to swap the complete quantum states of the local processors in parallel.