gebhart/patrepeval huggingface dataset:
Greatly enhanced inhibition of human immunodeficiency virus type 1 replication in CEM and HT4-6C cells by 3'-deoxythymidine diphosphate dimyristoylglycerol, a lipid prodrug of 3'-deoxythymidine (1992)

3'-Deoxythymidine (3dT) is a weakly active dideoxynucleoside in human immunodeficiency virus (HIV)-infected cells because of its slow phosphorylation by cellular thymidine kinase. 3dT diphosphate dimyristoylglycerol (3dTDP-DMG), a phospholipid prodrug, was synthesized and found in vitro to be 18- to 50-fold more effective than 3dT in CEM and HT4-6C cells. In CEM cells, the selectivity index of 3dTDP-DMG was 270 versus 48 for 3dT, an increase of 5.6-fold. In thymidine kinase-deficient mutant CEM cells infected with HIV, 3dT and zidovudine (AZT) were virtually inactive but 3dTDP-DMG retained substantial activity, suggesting that its greatly increased antiviral activity is due in part to bypass of thymidine kinase. 3dTDP-DMG was 14- to 37-fold more active than 3dT in AZT-sensitive and AZT-resistant clinical isolates of HIV; no cross-resistance with AZT was noted. The results suggest that lipid prodrugs may be utilized in some cases to confer unique metabolic advantages over the corresponding free nucleoside; in the case of 3dTDP-DMG, an 18- to 50-fold increase in antiretroviral activity was observed in LAV-infected cells. The strategy would seem to be especially useful for antiviral nucleosides which are poorly phosphorylated.
Higher-accuracy method for measuring minichromosome stability in Saccharomyces cerevisiae. (2002)

The minichromosome maintenance assay isfrequently used to characterize mutations genetically that affect the initiation of DNA replication or to decipherfunctional components in autonomously replicating sequences. The assay determines minichromosome loss by measuring the percentage of plasmid-containing cells in cultures after a period of growth in nonselective medium. Here we analyze data acquisition errors that contribute to the low accuracy of the routine versions of the assay. We propose modifications that eliminate errors in the acquisition of two variables and significantly improve the accuracy of the assay.
Paramyxovirus RNA editing and the requirement for hexamer genome length. (1996)

Paramyxoviruses cotranscriptionally edit their P gene mRNA by the programmed insertion of G residues into a short G run contained within a larger purine run, via pseudo-templated transcription. The templates for paramyxovirus transcription are genome nucleocapsids in which each nucleoprotein subunit is associated with 6 nt, and only genomes whose lengths are multiples of 6 are found naturally or are replicated efficiently in transfected cell systems. We have examined the effect of varying total genome length on the frequency and number of insertions into the mRNA editing site in a transfected cell system, using constructs that generate mini-genome analogues. We found that, as long as the purine run sequence and the region immediately upstream were unaltered, editing occurred during mRNA synthesis independent of the precise length of the minigenome. However, when mini-genome constructs whose lengths were not multiples of 6 were used, insertions (or deletions) occurred during antigenome synthesis within the purine run, which strikingly restored the hexamer length. Genome length correction due to changes in the antigenome purine run length occurred only when the mini-genome was not a multiple of 6, and these changes were only poorly affected by mutations in the mRNA editing site and the region immediately upstream. Our results suggest that the mRNA editing site is a natural hotspot for viral polymerase slippage during genome replication, and that this site serves the dual and complementary function of maintaining hexamer genome length. The unusual requirement of paramyxoviruses for genomes of precise hexamer length may have evolved to maintain genome stability against insertions in the mRNA editing site during replication.
Studies on stannous fluoride toothpaste and gel (2). Effects on salivary bacterial counts and plaque regrowth in vivo (1997)

There has been a resurgence of interest in stannous fluoride (SF) products in particular to provide oral hygiene and gingival health benefits. The aim of this study was to assess the persistence of antimicrobial action of a number of SF formulations in the mouth and relate these to plaque inhibitory activity. The formulations were 2 SF toothpastes (SF1, SF2), 2 SF plus stannous pyrophosphate toothpastes (SFSP1, SFSP2), a SF gel (G), a NaF toothpaste (C) and saline (S) as control. Both studies involve 2 different groups of 21 healthy dentate volunteers. The studies were single, blind, randomised, crossover designs balanced for residual effects, with a minimum 2 1/2 day washout period. Salivary bacterial counts were determined before and to 7 h after a single rinse with the formulations. Plaque regrowth from a zero baseline (day 1) was measured by index and area on day 5, after 2x daily rinsing with slurries of the formulations or saline. For bacterial counts, highly significant treatment differences were found. Bacterial counts were variably reduced by all treatments to 30 min then showed a variable rate of return towards baseline. All test agents were significantly better than S at some timepoints. The order for greatest persistence of action downwards was; (1) SFSP2; (2) SFSP1, G, and SF1; (3) SF2; (4) C; (5) S. Highly significant differences in plaque regrowth between treatments were found with similar mean ordering of efficacy as for salivary bacterial counts from most effective downwards namely; (1) SFSP1 and SFSP2; (2) SF1; (3) SF2; G and C; (4) S. The results were consistent with a parallel study measuring tea staining in vitro, whereby formulations causing the most staining produced the greatest persistence of action and plaque inhibitory activity. This suggests the availability of stannous ions was important for the clinical effects. It is concluded that stannous ions can enhance the plaque inhibitory action of toothpaste via a persistent antimicrobial action.
Foldable augmented maps (2010)

This paper presents folded surface detection and tracking for augmented maps. For the detection, plane detection is iteratively applied to 2D correspondences between an input image and a reference plane because the folded surface is composed of multiple planes. In order to compute the exact folding line from the detected planes, the intersection line of the planes is computed from their positional relationship. After the detection is done, each plane is individually tracked by frame-by-frame descriptor update. For a natural augmentation on the folded surface, we overlay virtual geographic data on each detected plane. The user can interact with the geographic data by finger pointing because the finger tip of the user is also detected during the tracking. As scenario of use, some interactions on the folded surface are introduced. Experimental results show the accuracy and performance of folded surface detection for evaluating the effectiveness of our approach.
Antagonism of CXCR3 Inhibits Lung Metastasis in a Murine Model of Metastatic Breast Cancer (2006)

Tumor cells aberrantly express chemokines and/or chemokine receptors, and some may promote tumor growth and metastasis. We examined the expression and function of chemokine receptor CXCR3 in a syngeneic murine model of metastatic breast cancer. By flow cytometry, CXCR3 was detected in all murine mammary tumor cell lines examined. All human breast cancer cell lines examined also expressed CXCR3, as did the immortalized but nontumorigenic MCF-10A cell line. Interaction of CXCR3 ligands, CXCL9, CXCL10, and CXCL11, with CXCR3 on the highly malignant murine mammary tumor cell line 66.1 resulted in intracellular calcium mobilization and chemotaxis in vitro. To test the hypothesis that tumor metastasis is facilitated by CXCR3 expressed by tumor cells, we employed a small molecular weight antagonist of CXCR3, AMG487. 66.1 tumor cells were pretreated with AMG487 prior to i.v. injection into immune-competent female mice. Antagonism of CXCR3 on 66.1 tumor cells inhibited experimental lung metastasis, and this antimetastatic activity was compromised in mice depleted of natural killer cells. Systemic administration of AMG487 also inhibited experimental lung metastasis. In contrast to the antimetastatic effect of AMG487, local growth of 66.1 mammary tumors was not affected by receptor antagonism. These studies indicate that murine mammary tumor cells express CXCR3 which facilitates the development of lung metastases. These studies also indicate for the first time that a small molecular weight antagonist of CXCR3 has the potential to inhibit tumor metastasis.
Multiple chromosomes carrying tumor suppressor activity for a uterine endometrial carcinoma cell line identified by microcell-mediated chromosome transfer. (1990)

Putative tumor suppressor genes can be mapped to specific chromosomes by the introduction of individual chromosomes derived from normal cells via microcell fusion. We have examined whether a highly malignant human uterine endometrial carcinoma cell line, HHUA, can be suppressed by only one normal chromosome or by multiple chromosomes. A library of mouse A9 clones containing different human chromosomes tagged with the pSV2-neo plasmid DNA were constructed. Transfer by microcell fusion of either chromosome 1, 6, 9, 11, or 19 into the HHUA tumor cell line was performed, and the abilities of the microcell hybrids to form tumors in nude mice were examined. The introduction of a chromosome 19 had no effect on the tumorigenicity of the cells, whereas microcell-hybrid clones with an introduced chromosome 1, 6 or 9 were completely suppressed for tumorigenicity. A decrease in tumor-take incidence in some but not all clones was observed following the introduction of a chromosome 11. The nontumorigenic microcell hybrids with an introduced chromosome 1 differed from the nontumorigenic microcell hybrids with an introduced chromosome 6, 9, or 11. A large percentage of hybrids with chromosome 1 senesced and/or showed alterations in cellular morphology and transformed growth properties in vitro. No growth or morphology alterations were observed following transfer of the other chromosomes. These results may indicate that more than one chromosome carries a tumor suppressor gene(s) for this human uterine endometrial carcinoma cell line and support the hypothesis that multiple tumor suppressor genes control the tumorigenic phenotype in the multistep process of neoplastic development.
Sterol side chain length and structure affect the clearance of chylomicron-like lipid emulsions in rats and mice (1998)

In previous work we found that sterols such as cholesterol were essential for physiological plasma clearance of lipid emulsions mimicking the structure of mammalian triglyceride-rich lipoproteins. In the present study we compared the clearances of emulsions prepared with sterols of varying alkyl chain length (straight chains, n-C3 to n-C7, or branched chains, i-C5 to i-C10) at the C-17 position. Our studies show that the length of the alkyl chain at the C-17 position of sterols markedly affects the removal of remnant particles from the plasma of rats traced by emulsion cholesteryl oleate label. An alkyl chain of 7 carbons or more was needed for normal remnant clearance. Straight and branched chains of similar length were cleared similarly, showing that the presence of a branch at the end of the alkyl chain had no effect on remnant clearance. For side chains of 7 carbons or less, substitution of sterols with an unsaturation in the alkyl chain close to the terminal carbon markedly decreased the clearance of remnants. Triolein label was used to estimate lipolysis of the injected emulsions. Lipolysis was little affected by the structure of the sterol side chain, except that lipolysis was markedly higher with emulsions containing sterols with an alkyl chain having 4 carbon atoms (n-C4) or with an unsaturation in the 4 carbon alkyl chain. We conclude that the length of the alkyl side chain is an important element in the essentiality of cholesterol as a regulator of metabolism of lipid emulsion models of triglyceride-rich lipoproteins.
Clinical significance of MLL-AF4 fusion transcript expression in the absence of a cytogenetically detectable t(4;11)(q21;q23) chromosomal translocation. (1998)

Leukemic cells from bone marrow (BM) of 17 infants and 127 children with newly diagnosed ALL, as well as fetal liver and BM and normal infant BM samples, were analyzed for presence of a t(4;11) translocation using standard cytogenetic techniques and expression of an MLL-AF4 fusion transcript using standard reverse transcriptase-polymerase chain reaction (RT-PCR) assays as well as nested RT-PCR that is 100-fold more sensitive than standard RT-PCR. Overall, 9 of 17 infants and 17 of 127 noninfant pediatric ALL patients were positive for expression of MLL-AF4 fusion transcripts, as determined by standard and/or nested RT-PCR assays. None of the MLL-AF4(+) cases were positive for E2A-PBX1 or BCR-ABL fusion transcript expression. Although 8 of 9 MLL-AF4(+) infants had cytogenetically detectable t(4;11)(q21;q23), 15 of the 17 MLL-AF4(+) noninfants were t(4;11)-. Infants with MLL-AF4(+) ALL had poor outcomes, whereas non-infant MLL-AF4(+)/t(4;11)- patients had favorable outcomes similar to MLL-AF4(-) patients. Notably, MLL-AF4 transcripts also were detected by nested RT-PCR in 4 of 16 fetal BMs, 5 of 13 fetal livers, and 1 of 6 normal infant BMs, but not in any of the 44 remission BM specimens from pediatric ALL patients. Our results provide unprecedented evidence that MLL-AF4 fusion transcripts can be present in normal hematopoietic cells, indicating that their expression is insufficient for leukemic transformation of normal lymphocyte precursors.
Studies in Organa-Fluorine Compounds : Part I. Synthesis of Some Substituted Glycines and Related Compounds of Potential Biological Activity (1969)

Several fluorine containing Ethyl-N-2-thiazolyl glycinates have been prepared and converted into glycylhydrazides. The latter have been condensed with various carbonyl compounds to yield substituted glycyl hydrazones. These are expected to display interesting biological properties.
QVECTOR: an algorithm for device-tailored quantum error correction (2017)

Current approaches to fault-tolerant quantum computation will not enable useful quantum computation on near-term devices of 50 to 100 qubits. Leading proposals, such as the color code and surface code schemes, must devote a large fraction of their physical quantum bits to quantum error correction. Building from recent quantum machine learning techniques, we propose an alternative approach to quantum error correction aimed at reducing this overhead, which can be implemented in existing quantum hardware and on a myriad of quantum computing architectures. This method aims to optimize the average fidelity of encoding and recovery circuits with respect to the actual noise in the device, as opposed to that of an artificial or approximate noise model. The quantum variational error corrector (QVECTOR) algorithm employs a quantum circuit with parameters that are variationally-optimized according to processed data originating from quantum sampling of the device, so as to learn encoding and error-recovery gate sequences. We develop this approach for the task of preserving quantum memory and analyze its performance with simulations. We find that, subject to phase damping noise, the simulated QVECTOR algorithm learns a three-qubit encoding and recovery which extend the effective T2 of a quantum memory six-fold. Subject to a continuous-time amplitude- plus phase-damping noise model on five qubits, the simulated QVECTOR algorithm learns encoding and decoding circuits which exploit the coherence among Pauli errors in the noise model to outperform the five-qubit stabilizer code and any other scheme that does not leverage such coherence. Both of these schemes can be implemented with existing hardware.
Preparation Techniques and Mechanisms of Formation of Biodegradable Nanoparticles from Preformed Polymers (1998)

The techniques available to prepare biodegradable nanoparticles (nanospheres and nanocapsules) from preformed polymers are reviewed. Although there is abundant literature on this topic, only a few focus on the thorough analysis of preparative procedures. In particular, four techniques are discussed in terms of their technological advantages and drawbacks: emulsification evaporation, solvent displacement, salting-out, and emulsification diffusion. The proposed mechanism of nanoparticle formation for each technique is described from a physicochemical perspective. The effects of preparative variables on nanoparticle size and drug-entrapment efficiency are also discussed.
Superconducting phase qubits (2009)

Experimental progress is reviewed for superconducting phase qubit research at the University of California, Santa Barbara. The phase qubit has a potential advantage of scalability, based on the low impedance of the device and the ability to microfabricate complex “quantum integrated circuits”. Single and coupled qubit experiments, including qubits coupled to resonators, are reviewed along with a discussion of the strategy leading to these experiments. All currently known sources of qubit decoherence are summarized, including energy decay (T 1), dephasing (T 2), and measurement errors. A detailed description is given for our fabrication process and control electronics, which is directly scalable. With the demonstration of the basic operations needed for quantum computation, more complex algorithms are now within reach.
Astonishing Diversity of Natural Peroxides as Potential Therapeutic Agents (2014)

Peroxides are an interesting group among biological active natural compounds. These metabolites contain a peroxide group (-O-O-) in which each oxygen atom is bonded to the other oxygen and to another atom. β-Oxygen in hydroperoxide group is considered as more active. Present review describes research on more than 230 natural peroxides isolated from plants, algae, and fungi. Intensive searches for new classes of biologically active metabolites produced by terrestrial and marine origin have resulted in the discovery of dozens of compounds possessing high antimalarial, antibacterial, cytotoxic, and other pharmacological activities as an important source of leads for drug discovery.
M-CSF-induced macropinocytosis increases solute endocytosis but not receptor-mediated endocytosis in mouse macrophages (1992)

Although coated vesicles can mediate both solute and receptor-mediated endocytosis, there are other kinds of endocytic vesicles that contribute to these processes. The relative contributions of these other organelles, particularly regarding solute influx, remains unsettled. Here we describe a physiological uncoupling of solute and receptor-mediated endocytosis that occurs during growth factor-stimulated macropinocytosis. We examined how recombinant human macrophage colony-stimulating factor (rM-CSF), which rapidly stimulates solute endocytosis in murine bone marrow-derived macrophages, affected ligand internalization via receptor-mediated endocytosis. Although rM-CSF stimulated internalization and accumulation of Lucifer Yellow (LY), a probe for solute endocytosis, it had no effect on accumulation of fluorescent acetylated low-density lipoprotein (acLDL), a ligand for the macrophage scavenger receptor, or on the endocytosis of 125I-labelled diferric transferrin. Video microscopy revealed that rM-CSF immediately induced active cell ruffling and the formation of phase-bright macropinosomes. Nocodazole pretreatment of macrophages inhibited both ruffling and macropinocytosis. Macropinosomes were fluorescently labelled by incubating macrophages briefly with probes for both solute endocytosis (fluorescent dextrans) and ligand endocytosis (fluorescein-labelled transferrin or diI-labelled acLDL). Macrophages incubated for one or two minutes formed macropinosomes that were labelled predominantly with the fluorescent solute probes but with little or none of the ligand probes; the latter were localized within smaller pinosomes. When cells pulsed with the fluorescent probes were washed and chased for an additional two minutes, solute and ligand probes occasionally co-localized in macropinosomes. Nocodazole inhibited macropinocytosis with little apparent effect on endocytosis via smaller vesicles. These experiments show that macropinosome formation is dependent on microtubules and also that the macropinosomes induced by rM-CSF are solute-rich and receptor-poor. Macropinosomes differ from coated vesicles in these respects, and therefore provide a physiologically regulated mechanism for uncoupling solute and receptor-mediated endocytosis.
인삼사포닌의 계면활성 및 생체 분자와의 작용 : ( 5 ) 미토콘드리아 Cytochrome c 단리에서 인삼사포닌의 추출효과 (1995)

생체막단백질 분리 및 정제시 사용되는 전형적인 계면활성체들의 대용으로 계면활성을 지닌 식물사포닌의 사용가능성을 인삼 및 도라지사포닌에 의한 소심장 미토콘드리아 막단백질인 cytochrome c 추출효과로써 검토하였다. 이 추출효과는 막단백질 분리에 일반적으로 사용되는 고가의 계면활성제인 digitonin과 n-dodecyl-β-D-maltoside(DMS)에 의한 추출효과와 비교하였다. Digitonin과 DMS에 의한 cytochrome c 추출은 각각 0.77, 4.06 nmole/mg·protein 정도이고 인삼사포닌은 1.82 nmole/mg·protein 정도의 추출효과가 확인되었다. 즉, 인삼사포닌은 막단백질 cytochrome c 추출에서 DMS 의 효과에는 미치지 못하나 digitonin 보다는 더 좋은 추출결과를 보여주고 있다. 따라서 본 연구는 막단백질의 분리정제시 사용되어온 계면활성제 대용으로 인삼사포닌의 사용 가능성을 충분히 보여주고 있다. 그러나 도라지사포닌에 의한 cytochrome c 추출효과는 관찰되지 않았다.
Cluster formation in the vapor produced by laser pulsing of the Y1Ba2Cu3O7 superconducting solid (1992)

Formation of neutral clusters in the vapor plume generated by laser-pulse heating of YBa2Cu3O7−x in vacuum was investigated. A Nd-glass laser of 1060 nm wavelength and 1.75 ms pulse width was used to generate peak power densities in the range of 104–105 W/cm2 over an area of 3–28 mm2. Time-of-flight mass spectrometry was used to identify neutral species contained in the plume and quadrupole mass spectrometry provided the time variation of the signal of several low-mass species. In both cases a transient optical pyrometer was used to monitor the surface temperature of the target during the laser pulse. At power densities generating peak surface temperatures less than 2300 K, the vapor consisted primarily of monomer species O, O2, Cu, Ba, BaO, and the dimer (BaO)2. At higher-power densities the major part of the vapor was made up of clusters of mass up to and beyond 3500 amu. These observations were complemented by microscopic examination of deposited plumes. Thin films of the target material were deposited on silicon and graphite substrates and examined by atomic force microscopy and scanning tunneling microscopy. Clusters 3 nm in diameter were observed in submonolayer films. Films of ≳∼100 nm were made up of stacks of such clusters. Very few liquid droplets from direct ejection from the target surface were observed. In-flight illumination of the plume by light from the laser did not significantly affect the mass distribution in the plumes; however, cluster formation at high-laser-power density (∼1012 W/cm2) was much lower than at 105 W/cm2.
Ryanodine Receptors: Structure, Expression, Molecular Details, and Function in Calcium Release (2010)

Ryanodine receptors (RyRs) are located in the sarcoplasmic/endoplasmic reticulum membrane and are responsible for the release of Ca(2+) from intracellular stores during excitation-contraction coupling in both cardiac and skeletal muscle. RyRs are the largest known ion channels (> 2MDa) and exist as three mammalian isoforms (RyR 1-3), all of which are homotetrameric proteins that interact with and are regulated by phosphorylation, redox modifications, and a variety of small proteins and ions. Most RyR channel modulators interact with the large cytoplasmic domain whereas the carboxy-terminal portion of the protein forms the ion-conducting pore. Mutations in RyR2 are associated with human disorders such as catecholaminergic polymorphic ventricular tachycardia whereas mutations in RyR1 underlie diseases such as central core disease and malignant hyperthermia. This chapter examines the current concepts of the structure, function and regulation of RyRs and assesses the current state of understanding of their roles in associated disorders.