gebhart/patrepeval huggingface dataset:
Inhibitory Effects of Acyclic Nucleoside Phosphonate Analogues on Hepatitis B Virus DNA Synthesis in HB611 Cells (1994)

By using an assay system based on a human hepatoblastoma cell line (HB611) that continuously synthesizes hepatitis B virus (HBV) DNA, 56 acyclic nucleoside phosphonate analogues were examined for their inhibitory effects on HBV DNA synthesis. The following compounds were found to inhibit HBV DNA synthesis at concentrations that were significantly lower than their minimum cytotoxic concentrations; 9-(2-phosphonylmethoxyethyl)adenine (PMEA), 9-(2-phosphonylmethoxyethyl) guanine(PMEG), 9-(2-phosphonylmethoxyethyl) guanine ethyl ester (PMEGEE), 9 - (2 - phosphonylmethoxyethyl) - 1 - deazaadenine (PMEC 1 A), 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP), ( S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA), 9-(3-isopropoxy-2-phosphonylmethoxypropyl)adenine (IPPMPA), 9-( RS)-(2-phosphonylmethoxypropyl)adenine (PMPA) and 9-(3-hydroxy-2-phosphonylmethoxypropyl)-2, 6-diaminopurine (HPMPDAP). The most selective compounds (with indexes greater than 100) were PMEDAP, PMEA, IPPMPA, and PMPA. Acyclic pyrimidine nucleoside phosphonate analogues did not prove markedly selective as anti-HBV agents. Diphosphoryl derivatives of some acyclic purine nucleoside phos-phonates (i.e. PMEA, PMEDAP, HPMPA) were prepared. They proved inhibitory to HBV DNA polymerase but not cellular DNA polymerase α.
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing (1995)

SUMMARY The common approach to the multiplicity problem calls for controlling the familywise error rate (FWER). This approach, though, has faults, and we point out a few. A different approach to problems of multiple significance testing is presented. It calls for controlling the expected proportion of falsely rejected hypotheses — the false discovery rate. This error rate is equivalent to the FWER when all hypotheses are true but is smaller otherwise. Therefore, in problems where the control of the false discovery rate rather than that of the FWER is desired, there is potential for a gain in power. A simple sequential Bonferronitype procedure is proved to control the false discovery rate for independent test statistics, and a simulation study shows that the gain in power is substantial. The use of the new procedure and the appropriateness of the criterion are illustrated with examples.
Identification and analysis of MHC class II DRB1 (Patr‐DRB1) alleles in chimpanzees (2006)

Abstract The MHC‐DRB1 gene is known to display the most extensive allelic polymorphisms among MHC class II genes. We attempted the selective identification of chimpanzee ( Pan troglodytes ) DRB1 (Patr‐DRB1) alleles using the polymerase chain reaction (PCR) technique in three steps: first, we performed Patr‐DRB1*02 lineage‐specific 8‐kb PCR for *02 lineage detection in each chimpanzee; second, we performed 620‐bp PCR for amplification of full‐length exon 2; and finally, we carried out an insert check using the pattern of microsatellite repeat length variability. In the genomic DNA of 23 chimpanzees, nine Patr‐DRB1 alleles containing two new alleles were detected. Our approach provides a relatively effective method of identifying Patr‐DRB1 alleles in individual chimpanzees and should also contribute to our understanding of the features of MHC molecules in non‐human primates.
The Role of Antigen Spreading in the Efficacy of Immunotherapies (2020)

The introduction and the unexpected efficacy of checkpoint inhibitors (CPI) and more recently of chimeric antigen receptor T cells (CAR T-cells) in the treatment of malignant diseases boosted the efforts in the development and clinical application of immunotherapeutic approaches. However, the definition of predictive factors associated with clinical responses as well as the identification of underlying mechanisms that promote the therapeutic efficacy remain to be determined. Starting from the first immunotherapeutic trials, it became evident that vaccine-induced tumor-specific T cells or the adoptive transfer of <i>ex vivo</i>-expanded T lymphocytes can recognize and eliminate malignant cells leading to long-lasting remissions in some patients. In addition, a phenomenon called epitope spreading, which was observed in responding patients, seemed to increase the efficiency possibly representing an important predictive factor. This review will focus on experimental and clinical evidence for the induction of epitope spreading and its role in the maintenance of an efficient antitumor immune response in cancer immunotherapy.
A learning algorithm for visual pose estimation of continuum robots (2011)

Continuum robots offer significant advantages for surgical intervention due to their down-scalability, dexterity, and structural flexibility. While structural compliance offers a passive way to guard against trauma, it necessitates robust methods for online estimation of the robot configuration in order to enable precise position and manipulation control. In this paper, we address the pose estimation problem by applying a novel mapping of the robot configuration to a feature descriptor space using stereo vision. We generate a mapping of known features through a supervised learning algorithm that relates the feature descriptor to known ground truth. Features are represented in a reduced sub-space, which we call eigen-features. The descriptor provides some robustness to occlusions, which are inherent to surgical environments, and the methodology that we describe can be applied to multi-segment continuum robots for closed-loop control. Experimental validation on a single-segment continuum robot demonstrates the robustness and efficacy of the algorithm for configuration estimation. Results show that the errors are in the range of 1°.
Labeling strategies in mass spectrometry-based protein quantitation (2009)

Mass spectrometry-based techniques for relative and absolute protein quantitation have advanced greatly over the past decade. New measurement strategies and improvements to existing methodologies have expanded the utility of mass spectrometry-based characterization of protein expression profiles, in particular by targeting a diverse array of chemical functionality (e.g. post-translational modifications, specific amino acid residues, etc.) by selective stable isotope incorporation. This article focuses on current trends in stable isotope labeling for protein quantitation using enzymatic, metabolic, and chemical derivatization techniques. Furthermore, new advances in phosphoproteomic labeling and lanthanide-based labeling methods are described.
Fast Multipole Boundary Element Method (2009)

The fast multipole method is one of the most important algorithms in computing developed in the 20th century. Along with the fast multipole method, the boundary element method (BEM) has also emerged as a powerful method for modeling large-scale problems. BEM models with millions of unknowns on the boundary can now be solved on desktop computers using the fast multipole BEM. This is the first book on the fast multipole BEM, which brings together the classical theories in BEM formulations and the recent development of the fast multipole method. Two- and three-dimensional potential, elastostatic, Stokes flow, and acoustic wave problems are covered, supplemented with exercise problems and computer source codes. Applications in modeling nanocomposite materials, bio-materials, fuel cells, acoustic waves, and image-based simulations are demonstrated to show the potential of the fast multipole BEM. Enables students, researchers, and engineers to learn the BEM and fast multipole method from a single source.
Beguiled: Free Exercise Exemptions and the Siren Song of Liberalism (1991)

From all the talk about our religious pluralism—how extensive, indelible, inarbitrable it is—one would expect that establishing one definition of religious liberty would be the mother of all civic disturbances. Wrong. We have a common definition of religious liberty. I can demonstrate our agreement with one exhibit: the immensely broad based denunciation of the 1990 Supreme Court decision, Employment Division v. Smith. Two counsellors at a drug rehabilitation center (Alfred Smith and Galen Black) appealed Oregon’s denial of unemployment benefits. Oregon cited the “misconduct” that led to their discharges. Their “misconduct” consisted of using the hallucinogenic drug peyote. Peyote was on Oregon’s list of controlled substances; using it was criminal. By ingesting it, Smith and Black also violated the specific terms of their employment. Each was a recovering substance abuser. Each had previously agreed to remain absolutely drug free.
Survival benefit needed to undergo chemotherapy: Patient and physician preferences (2017)

Among patients who received contemporary adjuvant chemotherapy in a randomized controlled trial, we found substantial variation in preferences regarding benefits that justified undergoing chemotherapy. Differences between patients' and physicians' choices were also apparent. Eliciting preferences regarding risks and benefits of adjuvant chemotherapy is critical. Cancer 2017;123:2821-28. © 2017 American Cancer Society.
Validating novel tau positron emission tomography tracer [F‐18]‐AV‐1451 (T807) on postmortem brain tissue (2015)

Our data suggest that [F-18]-AV-1451 holds promise as a surrogate marker for the detection of brain tau pathology in the form of tangles and paired helical filament-tau-containing neurites in Alzheimer brains but also point to its relatively lower affinity for lesions primarily made of straight tau filaments in non-Alzheimer tauopathy cases and to the existence of some [F-18]-AV-1451 off-target binding. These findings provide important insights for interpreting in vivo patterns of [F-18]-AV-1451 retention.
Multiple cis regulatory elements for maximal expression of the cauliflower mosaic virus 35S promoter in transgenic plants. (1989)

The 35S promoter is a major promoter of the cauliflower mosaic virus that infects crucifers. This promoter is still active when excised from cauliflower mosaic virus and integrated into the nuclear genome of transgenic tobacco. Previous work has shown that the -343 to -46 upstream fragment is responsible for the majority of the 35S promoter strength (Odell, J.T., Nagy, F., and Chua, N.-H. [1985]. Nature 313, 810-812). Here we show by 5', 3', and internal deletions that this upstream fragment can be subdivided into three functional regions, -343 to -208, -208 to -90, and -90 to -46. The first two regions can potentiate transcriptional activity when tested with the appropriate 35S promoter sequence. In contrast, the -90 to -46 region by itself has little activity but it plays an accessory role by increasing transcriptional activity of the two distal regions. Finally, we show that monomers and multimers of a 35S fragment (-209 to -46) can act as enhancers to potentiate transcription from a heterologous promoter.
Human Microsomal Prostaglandin E Synthase-1 (2003)

Human, microsomal, and glutathione-dependent prostaglandin (PG) E synthase-1 (mPGES-1) was expressed with a histidine tag in Escherichia coli. mPGES-1 was purified to apparent homogeneity from Triton X-100-solubilized bacterial extracts by a combination of hydroxyapatite and immobilized metal affinity chromatography. The purified enzyme displayed rapid glutathione-dependent conversion of PGH2 to PGE2 (Vmax; 170 micromol min-1 mg-1) and high kcat/Km (310 mm-1 s-1). Purified mPGES-1 also catalyzed glutathione-dependent conversion of PGG2 to 15-hydroperoxy-PGE2 (Vmax; 250 micromol min-1 mg-1). The formation of 15-hydroperoxy-PGE2 represents an alternative pathway for the synthesis of PGE2, which requires further investigation. Purified mPGES-1 also catalyzed glutathione-dependent peroxidase activity toward cumene hydroperoxide (0.17 micromol min-1 mg-1), 5-hydroperoxyeicosatetraenoic acid (0.043 micromol min-1 mg-1), and 15-hydroperoxy-PGE2 (0.04 micromol min-1 mg-1). In addition, purified mPGES-1 catalyzed slow but significant conjugation of 1-chloro-2,4-dinitrobenzene to glutathione (0.8 micromol min-1 mg-1). These activities likely represent the evolutionary relationship to microsomal glutathione transferases. Two-dimensional crystals of purified mPGES-1 were prepared, and the projection map determined by electron crystallography demonstrated that microsomal PGES-1 constitutes a trimer in the crystal, i.e. an organization similar to the microsomal glutathione transferase 1. Hydrodynamic studies of the mPGES-1-Triton X-100 complex demonstrated a sedimentation coefficient of 4.1 S, a partial specific volume of 0.891 cm3/g, and a Stokes radius of 5.09 nm corresponding to a calculated molecular weight of 215,000. This molecular weight, including bound Triton X-100 (2.8 g/g protein), is fully consistent with a trimeric organization of mPGES-1.
Tunnel Construction and Environmental Protection (2012)

Highway tunnel is one part of the road project among highways located in the mountain areas, the mileage proportion covered by tunnels has become larger and larger, and naturally, tunnel has become an important part in highway construction. However, the environmental influence brought about by the tunnel construction deserves more attention. Combined with the particular environment of highway tunnel construction in northwest mountain areas of Hubei , this thesis accordingly puts forward the structure system of environmental organization, and some measures as well as suggestions on environmental protection, and aims at providing reference for environmental work of highway tunnel construction in mountain areas.
Sequencing the Human Genome (1986)

The title of the report by R. Myerowitz and N. Hogikyan on page 1646 of the issue of 27 June was incorrect. It should have been "Different mutations in Ashkenazi Jews and non-Jewish French Canadians with Tay-Sachs disease."
Transcriptional modulator ZBED6 affects cell cycle and growth of human colorectal cancer cells (2015)

The transcription factor ZBED6 (zinc finger, BED-type containing 6) is a repressor of IGF2 whose action impacts development, cell proliferation, and growth in placental mammals. In human colorectal cancers, IGF2 overexpression is mutually exclusive with somatic mutations in PI3K signaling components, providing genetic evidence for a role in the PI3K pathway. To understand the role of ZBED6 in tumorigenesis, we engineered and validated somatic cell ZBED6 knock-outs in the human colorectal cancer cell lines RKO and HCT116. Ablation of ZBED6 affected the cell cycle and led to increased growth rate in RKO cells but reduced growth in HCT116 cells. This striking difference was reflected in the transcriptome analyses, which revealed enrichment of cell-cycle-related processes among differentially expressed genes in both cell lines, but the direction of change often differed between the cell lines. ChIP sequencing analyses displayed enrichment of ZBED6 binding at genes up-regulated in ZBED6-knockout clones, consistent with the view that ZBED6 modulates gene expression primarily by repressing transcription. Ten differentially expressed genes were identified as putative direct gene targets, and their down-regulation by ZBED6 was validated experimentally. Eight of these genes were linked to the Wnt, Hippo, TGF-β, EGF receptor, or PI3K pathways, all involved in colorectal cancer development. The results of this study show that the effect of ZBED6 on tumor development depends on the genetic background and the transcriptional state of its target genes.
Differential effects of the 5HT1B/1D receptor agonist naratriptan on trigeminal versus spinal nociceptive responses (1998)

In vivo electrophysiological assays in anesthetized rats have been used to compare the effects of the 5HT1B/1D receptor agonist, naratriptan, on central trigeminal nociceptive processing from dural and cutaneous inputs with its effects on nociceptive processing in the spinal cord. Naratriptan inhibited responses of single trigeminal neurons, to noxious electrical and mechanical stimulation of the dura and face, dose dependently by a maximum of 67+/-3% and 70+/-18%, respectively, at 3 mg kg(-1) i.v. In contrast, naratriptan did not affect spinal dorsal horn neuronal responses to noxious mechanical stimulation of the hind-paw. These findings suggest that 5HT1B/1D receptors have differential effects on nociceptive processing in the trigeminal versus spinal dorsal horns and provide a potential explanation for the lack of general analgesic effects of brain penetrant 5HT(1B/1D) agonist antimigraine drugs.
A family of zero current switching switched-capacitor dc-dc converters (2010)

This paper presents a new zero current switching (ZCS) technique for a family of switched-capacitor dc-dc converters. Compared to the traditional ZCS switched-capacitor dc-dc converters by inserting a magnetic core in the circuit, these new ZCS switched-capacitor dc-dc converters employ the stray inductance present in the circuit as the resonant inductor and provide soft switching for the devices. These ZCS switched-capacitor dc-dc converters do not utilize any additional components to minimize switching loss and reduce the current and voltage spike, thus leading to high efficiency and reliable benefit over traditional switched-capacitor dc-dc converters. Moreover, the bulky capacitor bank existing in traditional switched-capacitor circuits for high power high current application to achieve high efficiency was reduced significantly. Small size, low capacitance, low ESR, high current rating and high temperature rating ceramic capacitors can be employed. Therefore, by using proposed ZCS technique, small size, high power density, high efficiency, high temperature rating, and high current rating switched-capacitor dc-dc converter could be built. Simulation and experimental results are given to demonstrate the validity and features of the soft switching switched-capacitor dc-dc converters.
Fabrication of Plastic Microfluid Channels by Imprinting Methods (1997)

Microfluidic devices have been fabricated on poly(methyl methacrylate) substrates by two independent imprinting techniques. First-generation devices were fabricated using a small-diameter wire to create an impression in plastics softened by low-temperature heating. The resulting devices are limited to only simple linear channel designs but are readily produced at low cost. Second-generation devices with more complex microchannel arrangements were fabricated by imprinting the plastic substrates using an inverse three-dimensional image of the device micromachined on a silicon wafer. This micromachined template may be used repeatedly to generate devices reproducibly. Fluorescent analtyes were used to demonstrate reproducible electrophoretic injections. An immunoassay was also performed in an imprinted device as a demonstration of future applications.
Identification and Biochemical Characterization of a Novel Nortriterpene Inhibitor of the Human Lymphocyte Voltage-Gated Potassium Channel, Kv1.3 (1999)

A novel nortriterpene, termed correolide, purified from the tree Spachea correae, inhibits Kv1.3, a Shaker-type delayed rectifier potassium channel present in human T lymphocytes. Correolide inhibits 86Rb+ efflux through Kv1.3 channels expressed in CHO cells (IC50 86 nM; Hill coefficient 1) and displays a defined structure-activity relationship. Potency in this assay increases with preincubation time and with time after channel opening. Correolide displays marked selectivity against numerous receptors and voltage- and ligand-gated ion channels. Although correolide is most potent as a Kv1.3 inhibitor, it blocks all other members of the Kv1 family with 4-14-fold lower potency. C20-29-[3H]dihydrocorreolide (diTC) was prepared and shown to bind in a specific, saturable, and reversible fashion (Kd = 11 nM) to a single class of sites in membranes prepared from CHO/Kv1.3 cells. The molecular pharmacology and stoichiometry of this binding reaction suggest that one diTC site is present per Kv1.3 channel tetramer. This site is allosterically coupled to peptide and potassium binding sites in the pore of the channel. DiTC binding to human brain synaptic membranes identifies channels composed of other Kv1 family members. Correolide depolarizes human T cells to the same extent as peptidyl inhibitors of Kv1.3, suggesting that it is a candidate for development as an immunosuppressant. Correolide is the first potent, small molecule inhibitor of Kv1 series channels to be identified from a natural product source and will be useful as a probe for studying potassium channel structure and the physiological role of such channels in target tissues of interest.
A 25-kilodalton ubiquitin carrier protein (E2) catalyzes multi-ubiquitin chain synthesis via lysine 48 of ubiquitin. (1990)

Target protein multi-ubiquitination involving lysine 48 of ubiquitin (Ub) is known to occur during protein degradation in the ATP- and Ub-dependent proteolytic pathway (Chau, V., Tobias, J. W., Bachmair, A., Marriott, D., Ecker, D. J., Gonda, D. K., and Varshavsky, A. (1989) Science 243, 1576-1583). However, little is known about the enzymatic mechanism of multi-ubiquitination. We show that a purified Ub carrier protein, E2(25)K, catalyzes multi-Ub chain synthesis from purified Ub. Incubation of E2(25)K with Ub activating enzyme (E1), MgATP, and radiolabeled Ub (Mr = 8500) resulted in time dependent appearance of a "ladder" of radiolabeled Ub conjugates with molecular masses of 8.5n kDa, where n = 1, 2, 3, 4... (up to at least n = 10). The kinetics of this conjugative process were consistent with Ub2 acting as a steady-state intermediate. The putative Ub2 product of E2(25)K catalysis was purified and cleaved with a partially purified isopeptidase preparation. The sole cleavage product (Mr = 8500) had a tryptic digest identical to that of authentic Ub, confirming that the original conjugate was Ub2. Tryptic digestion of intact Ub2 gave products consistent with the existence of an isopeptide linkage between the COOH terminus of one Ub and Lys-48 of the other; this structure was confirmed by sequence analysis of the unique Ub2 tryptic fragment. Tryptic digestion of higher order Ubn adducts (n greater than or equal to 4) yielded fragments identical to those of Ub2, indicating that E2(25)K ligates successive Ub molecules primarily or exclusively via Lys-48. Although several other E2s supported synthesis of an apparent Ub2 adduct of undetermined linkage, only E2(25)K was capable of synthesizing multi-Ub chains from isolated Ub. Quantitative analysis of single turnovers showed that transfer from E2(25)K-Ub to Ub and Ub2 occurred with kappa 2 = 488 and 1170 M-1 min-1, respectively, at pH 7.3 and 37 degrees C. These results show that increasing the number of Ub molecules in a chain increases susceptibility to further ubiquitination by E2(25)K. Ub2 was a good substrate for activation by E1 and was readily transferred to E2(25)K. The labile E2(25)K-Ub2 adduct was catalytically active, and exhibited preference for Ub2 (versus Ub) as acceptor. These results suggest that E2(25)K may function as a multi-ubiquitinating enzyme in the Ub-dependent proteolytic pathway.
Photoinduced birefringence in optical fibers: a comparative study of low-birefringence and high-birefringence fibers (1992)

A study of photoinduced birefringence in bow-tie (stress-induced) high-birefringence (Hi-Bi) and low-birefringence (Lo-Bi) germanosilicate optical fibers is conducted by using 532-nm light. The study reveals that Hi-Bi fibers are insensitive to light polarized along the fast axis, in contrast to Lo-Bi fibers, which are photosensitive along both axes. The induced birefringence in Lo-Bi fibers is reversible, whereas the change in Hi-Bi fibers is permanent. The sign of the induced birefringence is established experimentally for the first time to our knowledge, and the significance of the results to models based on stress and/or glass defects is briefly discussed.