gebhart/patrepeval huggingface dataset:
Enzyme Inhibition and Protein-Binding Action of the Procyanidin-Rich French Maritime Pine Bark Extract, Pycnogenol:  Effect on Xanthine Oxidase (2000)

Pycnogenol, an extract from French maritime pine bark (PBE), is a complex mixture of bioflavonoids with reported protective effects against disease. PBE is an effective scavenger of reactive oxygen species, and its main constituents are procyanidins of various chain lengths. To find out the biochemical basis of action of PBE on enzyme activity, involvement of its redox activity and direct binding to the enzyme in its subsequent action on enzyme activity have been investigated. PBE dose-dependently inhibited the activities of xanthine oxidase, xanthine dehydrogenase, horseradish peroxidase, and lipoxygenase, but it did not affect the activities of glucose oxidase, ascorbate oxidase, or elastase. To characterize the mechanism of PBE action, studies were focused on xanthine oxidase and glucose oxidase. Under non-denaturing conditions, PBE changed the electrophoretic mobility of xanthine oxidase but not of glucose oxidase. Gel filtration chromatography confirmed higher molecular weight complexes of xanthine oxidase and xanthine dehydrogenase in the presence of PBE. It was found that hydrophobic bonding might be the dominant mode of interaction between PBE and xanthine oxidase. The importance of the binding in the effect of PBE on enzyme activity was supported by the observation that PBE binds to and inhibits catalase, but not superoxide dismutase. However, no correlation was found between superoxide/hydroxyl radical scavenging activity and the inhibitory effect on xanthine oxidase activity of PBE, various purified flavonoids, or other complex mixtures of bioflavonoids. The results indicate that PBE selectively inhibits xanthine oxidase through binding to the enzyme rather than by the redox activity.
Controls of Tectonics on both Sedimentary Sequences and Petroleum Systems in Tarim Basin, Northwest China (2007)

序列的各种各样的订单从不顺从在 Tarim 盆被认出。三个大顺序的组，六大顺序，十六超级顺序并且 42 个序列从 Sinian 被决定到 Quanternary。大顺序、超级顺序根据发生在北方和 Tarim 板的南方边缘的局部地构造的事件。全球海水平变化仅仅工作了在构造地稳定的时期或在低顺序序列控制形成。到来源的有的靠近的关系摇的序列，水库和帽子岩石，和构造事件决定了烃的迁居，累积，和保藏。三个大顺序的组骑车，包括早周期 --Sinian 中间的泥盆纪，中间的周期上面泥盆纪三叠纪，并且迟了的周期 -- 侏罗记第四级，对应于三个水库形成周期。那么，本地构造事件在 Tarim 盆控制了序列和油和气体的分发，这能被结束。
Butyrate mediates decrease of histone acetylation centered on transcription start sites and down-regulation of associated genes (2007)

Butyrate is a histone deacetylase inhibitor (HDACi) with anti-neoplastic properties, which theoretically reactivates epigenetically silenced genes by increasing global histone acetylation. However, recent studies indicate that a similar number or even more genes are down-regulated than up-regulated by this drug. We treated hepatocarcinoma HepG2 cells with butyrate and characterized the levels of acetylation at DNA-bound histones H3 and H4 by ChIP-chip along the ENCODE regions. In contrast to the global increases of histone acetylation, many genomic regions close to transcription start sites were deacetylated after butyrate exposure. In order to validate these findings, we found that both butyrate and trichostatin A treatment resulted in histone deacetylation at selected regions, while nucleosome loss or changes in histone H3 lysine 4 trimethylation (H3K4me3) did not occur in such locations. Furthermore, similar histone deacetylation events were observed when colon adenocarcinoma HT-29 cells were treated with butyrate. In addition, genes with deacetylated promoters were down-regulated by butyrate, and this was mediated at the transcriptional level by affecting RNA polymerase II (POLR2A) initiation/elongation. Finally, the global increase in acetylated histones was preferentially localized to the nuclear periphery, indicating that it might not be associated to euchromatin. Our results are significant for the evaluation of HDACi as anti-tumourogenic drugs, suggesting that previous models of action might need to be revised, and provides an explanation for the frequently observed repression of many genes during HDACi treatment.
Differential regulation of interleukin 12 and interleukin 23 production in human dendritic cells (2008)

We analyzed interleukin (IL) 12 and IL-23 production by monocyte-derived dendritic cells (mono-DCs). Mycobacterium tuberculosis H37Rv and zymosan preferentially induced IL-23. IL-23 but not IL-12 was efficiently induced by the combination of nucleotide-binding oligodimerization domain and Toll-like receptor (TLR) 2 ligands, which mimics activation by M. tuberculosis, or by the human dectin-1 ligand beta-glucan alone or in combination with TLR2 ligands, mimicking induction by zymosan. TLR2 ligands inhibited IL-12 and increased IL-23 production. DC priming with interferon (IFN) gamma strongly increased IL-12 production, but was not required for IL-23 production and inhibited IL-23 production induced by beta-glucan. The pattern of IL-12 and IL-23 induction was reflected in accumulation of the IL-12p35 and IL-23p19 transcripts, respectively, but not IL-12/23p40. Although IL-23, transforming growth factor beta, and IL-6 contained in the supernatants of activated mono-DCs played a role in the induction of IL-17 by human CD4(+) T cells, IL-1beta, in combination with one or more of those factors, was required for IL-17 production, and its production determined the differential ability of the stimuli used to elicit mono-DCs to produce soluble factors directing IL-17 production. Thus, the differential ability of pathogens to induce antigen-presenting cells to produce cytokines regulates the immune response to infection.
Ultrasound affects distribution of plasminogen and tissuetype plasminogen activator in whole blood clots in vitro (2004)

Summary Ultrasound of 2 MHz frequency and 1.2 W/cm2 acoustic intensity was applied to examine the effect of sonication on recombinant tissue-type plasminogen activator (rt-PA)-induced thrombolysis as well as on the distribution of plasminogen and t-PA within whole blood clots in vitro. Thrombolysis was evaluated quantitatively by measuring clot weight reduction and the level of fibrin degradation product D-dimer (FDP-DD) in the supernatant. Weight reduction in the group of clots treated both with ultrasound and rt-PA was 35.2% ± 6.9% which is significantly higher (p&lt;0.0001) than in the group of clots treated with rt-PA only (19.9% ± 4.3%). FDP-DD level in the supernatants of the group treated with ultrasound and rt-PA increased sevenfold compared to the group treated with rt-PA alone, (14895 ± 2513 ng/ml vs. 2364 ± 725 ng/ml). Localization of fibrinolytic components within the clots was accomplished by using gel-entrapping technique and immunohistochemistry. Spatial distributions of t-PA and plasminogen showed clearly that ultrasound promoted the penetration of rt-PA into thrombi significantly (p&lt;0.0001), and broadened the zone of lysis from 8.9 ± 2.6 µm to 21.2 ± 7.2 µm. We speculate that ultrasound enhances thrombolysis by affecting the distribution of rt-PA within the clot.
Immune tolerance improves the efficacy of enzyme replacement therapy in canine mucopolysaccharidosis I (2008)

Mucopolysaccharidoses (MPSs) are lysosomal storage diseases caused by a deficit in the enzymes needed for glycosaminoglycan (GAG) degradation. Enzyme replacement therapy with recombinant human alpha-L-iduronidase successfully reduces lysosomal storage in canines and humans with iduronidase-deficient MPS I, but therapy usually also induces antibodies specific for the recombinant enzyme that could reduce its efficacy. To understand the potential impact of alpha-L-iduronidase-specific antibodies, we studied whether inducing antigen-specific immune tolerance to iduronidase could improve the effectiveness of recombinant iduronidase treatment in canines. A total of 24 canines with MPS I were either tolerized to iduronidase or left nontolerant. All canines received i.v. recombinant iduronidase at the FDA-approved human dose or a higher dose for 9-44 weeks. Nontolerized canines developed iduronidase-specific antibodies that proportionally reduced in vitro iduronidase uptake. Immune-tolerized canines achieved increased tissue enzyme levels at either dose in most nonreticular tissues and a greater reduction in tissue GAG levels, lysosomal pathology, and urinary GAG excretion. Tolerized MPS I dogs treated with the higher dose received some further benefit in the reduction of GAGs in tissues, urine, and the heart valve. Therefore, immune tolerance to iduronidase improved the efficacy of enzyme replacement therapy with recombinant iduronidase in canine MPS I and could potentially improve outcomes in patients with MPS I and other lysosomal storage diseases.
Semi-Supervised Support Vector Machines (1998)

We introduce a semi-supervised support vector machine (S3yM) method. Given a training set of labeled data and a working set of unlabeled data, S3YM constructs a support vector machine us-ing both the training and working sets. We use S3YM to solve the transduction problem using overall risk minimization (ORM) posed by Yapnik. The transduction problem is to estimate the value of a classification function at the given points in the working set. This contrasts with the standard inductive learning problem of estimating the classification function at all possible values and then using the fixed function to deduce the classes of the working set data. We propose a general S3YM model that minimizes both the misclassification error and the function capacity based on all the available data. We show how the S3YM model for I-norm lin-ear support vector machines can be converted to a mixed-integer program and then solved exactly using integer programming. Re-sults of S3YM and the standard I-norm support vector machine approach are compared on ten data sets. Our computational re-sults support the statistical learning theory results showing that incorporating working data improves generalization when insuffi-cient training information is available. In every case, S3YM either improved or showed no significant difference in generalization com-pared to the traditional approach. Semi-Supervised Support Vector Machines 369 1
OCT4 Expression Enhances Features of Cancer Stem Cells in a Mouse Model of Breast Cancer (2011)

The cancer stem cell (CSC) hypothesis proposes that CSCs are responsible for metastasis and disease recurrence. Therefore, targeting CSCs has the potential to significantly improve outcomes for cancer patients. The OCT4 transcription factor gene is a master gene that plays a key role in the self-renewal and pluripotency of stem cells. In this study, we introduced an OCT4 reporting vector into 4T1 mouse breast cancer cells and sorted OCT4 high and OCT4 low cell populations. We then determined whether OCT4 expression is associated with maintenance and expansion of CSCs. We found that OCT4(high) 4T1 cells have an increased ability to form tumorsphere and a high expression of stem cell markers such as Sca-1, CD133, CD34, and ALDH1, when compared with OCT4(low) 4T1 cells. In addition, OCT4(high) 4T1 cells have greater tumorigenic potential in vivo. These findings suggest that OCT4 expression may be a useful target for stem cell-specific cancer therapy.
Transmembrane Signaling by G Protein-Coupled Receptors (2006)

G protein-coupled receptors (GPCRs) make up the largest and most diverse family of membrane receptors in the human genome, relaying information about the presence of diverse extracellular stimuli to the cell interior. All known GPCRs share a common architecture of seven membrane-spanning helices connected by intra- and extracellular loops. Most GPCR-mediated cellular responses result from the receptor acting as a ligand-activated guanine nucleotide exchange factor for heterotrimeric guanine nucleotide-binding (G) proteins whose dissociated subunits activate effector enzymes or ion channels. GPCR signaling is subject to extensive negative regulation through receptor desensitization, sequestration, and down regulation, termination of G protein activation by GTPase-activation proteins, and enzymatic degradation of second messengers. Additional protein-protein interactions positively modulate GPCR signaling by influencing ligand-binding affinity and specificity, coupling between receptors, G proteins and effectors, or targeting to specific subcellular locations. These include the formation of GPCR homo- and heterodimers, the interaction of GPCRs with receptor activity-modifying proteins, and the binding of various scaffolding proteins to intracellular receptor domains. In some cases, these processes appear to generate signals in conjunction with, or even independent of, G protein activation.
Stimulus Generalization and Representation in Adaptive Network Models of Category Learning (1991)

An exponential-decay relationship between the probability of generalization and psychological distance has received considerable support from studies of stimulus generalization ( Shepard, 1958 ) and categorization ( Nosofsky, 1984 ). It is shown here how an approximate exponential generalization gradient emerges from stimulus representation assumptions isomorphic to a special case of Shepard's (1987) theory of stimulus generalization in a “configuralcue” network model of human learning that represents stimulus patterns in terms of elementary features and pairwise conjunctions of features ( Gluck &amp; Bower, 1988b ; Gluck, Bower, &amp; Hee, 1989 ). The network model can be viewed as a combination of Shepard's theory and an associative learning rule derived from Rescorla and Wagner's (1972) theory of classical conditioning.
Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody (2010)

Sclerostin, an osteocyte-secreted protein, negatively regulates osteoblasts and inhibits bone formation. In this first-in-human study, a sclerostin monoclonal antibody (AMG 785) was administered to healthy men and postmenopausal women. In this phase I, randomized, double-blind, placebo-controlled, ascending, single-dose study, 72 healthy subjects received AMG 785 or placebo (3:1) subcutaneously (0.1, 0.3, 1, 3, 5, or 10 mg/kg) or intravenously (1 or 5 mg/kg). Depending on dose, subjects were followed for up to 85 days. The effects of AMG 785 on safety and tolerability (primary objectives) and pharmacokinetics, bone turnover markers, and bone mineral density (secondary objectives) were evaluated. AMG 785 generally was well tolerated. One treatment-related serious adverse event of nonspecific hepatitis was reported and was resolved. No deaths or study discontinuations occurred. AMG 785 pharmacokinetics were nonlinear with dose. Dose-related increases in the bone-formation markers procollagen type 1 N-propeptide (P1NP), bone-specific alkaline phosphatase (BAP), and osteocalcin were observed, along with a dose-related decrease in the bone-resorption marker serum C-telopeptide (sCTx), resulting in a large anabolic window. In addition, statistically significant increases in bone mineral density of up to 5.3% at the lumbar spine and 2.8% at the total hip compared with placebo were observed on day 85. Six subjects in the higher-dose groups developed anti-AMG 785 antibodies, 2 of which were neutralizing, with no discernible effect on the pharmacokinetics or pharmacodynamics. In summary, single doses of AMG 785 generally were well tolerated, and the data support further clinical investigation of sclerostin inhibition as a potential therapeutic strategy for conditions that could benefit from increased bone formation.
NF-κB Signaling Differentially Regulates Influenza Virus RNA Synthesis (2008)

The NF-kappaB signaling pathway has previously been shown to be required for efficient influenza A virus replication, although the molecular mechanism is not well understood. In this study, we identified a specific step of the influenza virus life cycle that is influenced by NF-kappaB signaling by using two known NF-kappaB inhibitors and a variety of influenza virus-specific assays. The results of time course experiments suggest that the NF-kappaB inhibitors Bay11-7082 and ammonium pyrrolidinedithiocarbamate inhibited an early postentry step of viral infection, but they did not appear to affect the nucleocytoplasmic trafficking of the viral ribonucleoprotein complex. Instead, we found that the levels of influenza virus genomic RNA (vRNA), but not the corresponding cRNA or mRNA, were specifically reduced by the inhibitors in virus-infected cells, indicating that NF-kappaB signaling is intimately involved in the vRNA synthesis. Furthermore, we showed that the NF-kappaB inhibitors specifically diminished influenza virus RNA transcription from the cRNA promoter but not from the vRNA promoter in a reporter assay, a result which is consistent with data obtained from virus-infected cells. The overexpression of the p65 NF-kappaB molecule could not only eliminate the inhibition but also activate influenza virus RNA transcription from the cRNA promoter. Finally, using p65-specific small interfering RNA, we have shown that p65 knockdown reduced the levels of influenza virus replication and vRNA synthesis. In summary, we have provided evidence showing, for the first time, that the NF-kappaB host signaling pathway can differentially regulate influenza virus RNA synthesis, which may also offer some new perspectives into understanding the host regulation of RNA synthesis by other RNA viruses.
Numerical techniques for microwave and millimeter-wave passive structures (1989)

The Finite Element Method (J. Davies). Integral Equation Technique (J. Mosig). Planar Circuit Analysis (K. Gupta & M. Abouzahra). Spectral Domain Approach (T. Uwaro & T. Itoh). The Method of Lines (R. Pregla & W. Pascher). The Waveguide Model for the Analysis of Microstrip Discontinuities (I. Wolff). The Transmission Line Matrix (TLM) Method (W. Hoefer). The Mode--Matching Method (Y. Shih). Generalized Scattering Matrix Technique (T. Itoh). Transverse Resonance Technique (R. Sorrentino). Index.
Peptide display on filamentous phage capsids An new powerful tool to study protein—ligand interaction (1992)

Peptides can be displayed on the surface of filamentous bacteriophages by fusion to phage coat proteins. It was recently shown that vast (10(8)) collections of phages, each exposing a variant of the original peptide, can be constructed and utilized as a general source of peptide ligands. By panning these libraries on a target molecule linked to a solid support it is possible to select, out of the hundreds of millions of clones, those few phages that display a peptide that binds the target molecule. Searching these libraries is a powerful tool to be applied in many areas of fundamental and applied biology.
Neuroendocrine mechanisms regulating food intake and body weight (2000)

In the field of obesity research, two separate lines of study have emerged which explore the mechanism by which food intake is regulated: short-term control of food intake, and the central regulation of energy balance. The former studies the satiety response during consumption of meals, whereby satiety signalling originating in the gut is transduced into a neural signal that modulates satiety pathways in the brainstem. This review describes a neuroanatomically based model in which leptin and insulin signalling in the hypothalamus governs long-term regulation of energy balance via mechanisms that are integrated with satiety hormone signalling in the brainstem. The functional outcome of this integration is a cumulative meal-to-meal regulation of food intake, that over relatively long intervals serves to maintain stable adipose stores. Our model provides a context within which continued investigation of neuroendocrine mechanisms that control food intake and body weight can be explored, and has potential application to our current understanding of clinical obesity and its treatment.
A Long-Chain Secondary Alcohol Dehydrogenase from Rhodococcus erythropolis ATCC 4277 (1995)

A NAD-dependent secondary alcohol dehydrogenase has been purified from the alkane-degrading bacterium, Rhodococcus erythropolis ATCC 4277. The enzyme was found to be active against a broad range of substrates, particularly long-chain secondary aliphatic alcohols. Although optimal activity was observed with linear 2-alcohols containing between 6 and 11 carbon atoms, secondary alcohols as long as 2-tetradecanol were oxidized at 25% of the rate seen with mid-range alcohols. The purified enzyme was specific for the S-(+) stereoisomer of 2-octanol and had a specific activity for 2-octanol of over 200 (mu)mol/min/mg of protein at pH 9 and 37(deg)C, 25-fold higher than that of any previously reported S-(+) secondary alcohol dehydrogenase. Linear primary alcohols containing between 3 and 13 carbon atoms were utilized 20- to 40-fold less efficiently than the corresponding secondary alcohols. The apparent K(infm) value for NAD(sup+) with 2-octanol as the substrate was 260 (mu)M, whereas the apparent K(infm) values for the 2-alcohols ranged from over 5 mM for 2-pentanol to less than 2 (mu)M for 2-tetradecanol. The enzyme showed moderate thermostability (half-life of 4 h at 60(deg)C) and could potentially be useful for the synthesis of optically pure stereoisomers of secondary alcohols.
A low jitter 0.3-165 MHz CMOS PLL frequency synthesizer for 3 V/5 V operation (1997)

This paper describes a phase-locked loop (PLL) based frequency synthesizer. The voltage-controlled oscillator (VCO) utilizing a ring of single-ended current-steering amplifiers (CSA) provides low noise, wide operating frequencies, and operation over a wide range of power supply voltage. A programmable charge pump circuit automatically configures the loop gain and optimizes it over the whole frequency range. The measured PLL frequency ranges are 0.3-165 MHz and 0.3-100 MHz at 5 V and 3 V supplies, respectively (the VCO frequency is twice PLL output). The peak-to-peak jitter is 81 ps (13 ps rms) at 100 MHz. The chip is fabricated with a standard 0.8-/spl mu/m n-well CMOS process.
Evaluation of 3D Printing and Its Potential Impact on Biotechnology and the Chemical Sciences (2014)

Nearing 30 years since its introduction, 3D printing technology is set to revolutionize research and teaching laboratories. This feature encompasses the history of 3D printing, reviews various printing methods, and presents current applications. The authors offer an appraisal of the future direction and impact this technology will have on laboratory settings as 3D printers become more accessible.
Morphometry of intracellularly labeled neurons of the auditory nerve: Correlations with functional properties (1984)

Single auditory-nerve fibers were injected with horseradish peroxidase after their tuning properties, characteristic frequencies, and spontaneous discharge rates were measured. From these functional properties virtually all other aspects of auditory-nerve response can be predicted. Labeled fibers were reconstructed from the point of peripheral termination on cochlear hair cells to the point at which they enter the cochlear nucleus. Several morphological properties were measured at the light-microscopic level, including axonal diameter, axonal length, internodal distances, cell-body area, and cell-body shape. All of these parameters were correlated, though some weakly, with characteristic frequency. However, only axonal diameter was correlated with spontaneous discharge rate.
Biodegradable, Polymeric Nanoparticle Delivery Systems for Cancer Therapy (2007)

Nanotechnology has the potential to impact the treatment of cancer significantly. This review will explore how this potential is beginning to be realized through the design of polymeric nanoparticle delivery systems. Current research is focused on developing biocompatible nanoparticles capable of targeting specific cancer markers and delivering imaging and therapeutic agents for the detection and treatment of cancer, resulting in a number of preclinical and clinical applications. More sophisticated nanoparticle designs are now in development, including particles able to release multiple drugs for enhanced treatment efficacy and targeted, multifunctional particles capable of combining imaging and drug release.