gebhart/patrepeval huggingface dataset:
Understanding the Physical Interactions in the FGF21/FGFR/β‐Klotho Complex: Structural Requirements and Implications in FGF21 Signaling (2012)

The endocrine fibroblast growth factor 21 (FGF21) requires both fibroblast growth factor receptor (FGFR) and β-Klotho for signaling. In this study, we sought to understand the inter-molecular physical interactions in the FGF21/FGFR/β-Klotho complex by deleting key regions in FGFR1c or FGF21. Deletion of the D1 and the D1-D2 linker (the D1/linker region) from FGFR1c led to β-Klotho-independent receptor activation by FGF21, suggesting that there may be a direct interaction between FGF21 and the D1/linker region-deficient FGFR1c. Consistent with this, the extracellular portion of FGFR1c lacking the D1/linker region blocked FGF21 action in a reporter assay, presumably by binding to and sequestering FGF21 from acting on cell surface receptor complex. In addition, the D1/linker region-deficient FGFR1c had enhanced interaction with β-Klotho. Further, we demonstrated that deletion of the D1/linker region enhanced the formation of the FGF21/β-Klotho/FGFR1c ternary complex in both Biacore and asymmetrical flow field flow fractionation studies. Finally, we found that the N-terminus of FGF21 is involved in the interaction with FGFR1c and FGF21/β-Klotho/FGFR1c ternary complex formation. Taken together, our data suggest that the D1/linker region regulates both the FGF21/FGFR1c and FGFR1c/β-Klotho interaction, and a direct interaction of FGF21 with FGFR1c may be an important step in receptor-mediated FGF21 signaling.
Palladium-Catalyzed Synthesis of 9-Fluorenylidenes through Aryne Annulation (2009)

The palladium-catalyzed annulation of arynes by substituted o-halostyrenes produces substituted 9-fluorenylidenes in good yields. This methodology provides this important carbocyclic ring system in a single step, which involves the generation of two new carbon-carbon bonds, occurs under relatively mild reaction conditions, and tolerates a variety of functional groups, including cyano, ester, aldehyde, and ketone groups.
Genes controlling gp25/30 cell-surface molecules map to chromosomes X and Y and escape X-inactivation. (1985)

The monoclonal antibody AbO13 defines a cell-surface antigen that is expressed on most cultured human cells, but not on rodent cells. AbO13 precipitates glycoproteins of 25,000 and 30,000 mol. wt. from lysates of [3H]glucosamine-labeled human cells. Results of the serological typing of a panel of 25 rodent-human somatic cell hybrid clones show that reactivity with AbO13 segregates with the human X and Y chromosomes. The presence of either of these chromosomes is sufficient for O13 expression on the hybrid cell surface. Analysis of hybrid clones containing human X chromosomes with karyotypically defined deletions permitted the regional assignment of the X-linked gene locus controlling the expression of O13 to Xp22-pter. In addition, AbO13 is reactive with Chinese hamster-human hybrids derived from fibroblasts of a 49,XXXXX individual that contained only inactivated copies of the human X chromosome. These results suggest that the X-linked locus determining the expression of O13 is not subject to X-inactivation.
Successful PBSC Mobilization with High-Dose G-CSF for Patients Failing a First Round of Mobilization (1999)

PBSC are the preferred source of stem cells for autologous transplantation. However, regardless of the mobilization procedure used, 10%-20% of patients fail to collect an adequate number to ensure prompt engraftment. There is as yet no standard mobilization procedure for patients who fail a first mobilization attempt. Here, we describe a highly efficient strategy to obtain an adequate number of stem cells for patients who failed a first mobilization attempt. Seventy-four patients with various hematologic malignancies underwent initial mobilization with various regimens including hematopoietic growth factors with or without chemotherapy. In 72% of patients, > or =2 x 10(6) CD34+ stem cells/kg were collected in the initial mobilization attempt, and patients engrafted in a median of 10 days for neutrophils and 12 days for platelets. Eighteen patients failed to mobilize adequate numbers of stem cells, defined as the inability to collect 0.2 x 10(6) CD34+ stem cells/kg/day in the first 2-3 days. These patients had their apheresis halted. Patients were immediately given G-CSF (32 microg/kg/day) for 4 days as a second attempt at mobilization. Eighty-eight percent of these patients achieved the target of > or =2 x 10(6) CD34+ cells/kg, with a median duration of apheresis of 5 days (including the first and second mobilizations). The mean CD34+ cells/kg/day increased after administration of high-dose G-CSF from 0.16 after the first mobilization attempt to 0.61 (p = 0.0002) after the second mobilization. All patients engrafted in a median of 11 and 13 days for neutrophils and platelets, respectively. We conclude that patients whose apheresis yield is <0.4 x 10(6) CD34+ cells/kg after the first two apheresis collections can be successfully mobilized if high-dose G-CSF is administered immediately and continued until achieving > or =2 x 10(6) CD34+ stem cells/kg.
Mechanism of activation of bovine factor X (Stuart factor) by intrinsic and extrinsic pathways (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMechanism of activation of bovine factor X (Stuart factor) by intrinsic and extrinsic pathwaysKazuo Fujikawa, Michael H. Coan, Mark E. Legaz, and Earl W. DavieCite this: Biochemistry 1974, 13, 26, 5290–5299Publication Date (Print):December 1, 1974Publication History Published online1 May 2002Published inissue 1 December 1974https://pubs.acs.org/doi/10.1021/bi00723a006https://doi.org/10.1021/bi00723a006research-articleACS PublicationsRequest reuse permissionsArticle Views139Altmetric-Citations110LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
The basicities of substituted N-trimethylammoniophenylacetamidates and N-trimethylammoniocinnamamidates. The hammett correlations and the thermodynamics of protonation (1978)

The pKa values of a number of substituted N-trimethylammoniophenylacetamidates and N-trimethylammoniocinnamamidates have been determined over a range of temperature and the thermodynamic functions of protonation (ΔH° and ΔS°) derived. Both reaction series obey the Hammett equation very well, the ρ values at 25 °C being 0.639 ± 0.026 and 0.709 ± 0.049, respectively. It is found that the ratio of these ρ values to the ρ values for the ionization of the corresponding carboxylic acids is constant at 1.50 ± 0.04, regardless of the structure of the rest of the molecule, and is thus a characteristic of the amidate group. An analysis of the pKa data for these acid–base series and comparison with the pKa data for the corresponding carboxylic acid series leads to the conclusion that mesomeric electron donation by the benzene ring to the basic groups (a) and (b) is more important in the carboxylates than in the amidates, consistent with the greater overall electronegativity of the carboxylate group. The thermodynamic functions of protonation, ΔH° and ΔS°, broadly show a similar behaviour to that of the N-trimethylammoniobenzamidate series, although the entropies of protonation are more positive.
Neural network architecture for control (1988)

Two important computational features of neural networks are associative storage and retrieval of knowledge, and uniform rate of convergence of network dynamics independent of network dimension. It is indicated how these properties can be used for adaptive control through the use of neural network computation algorithms, and resulting computational advantages are outlined. The neuromorphic control approach is compared to model reference adaptive control on a specific example. It is shown that the utilization of neural networks for adaptive control offers definite speed advantages over traditional approaches for very-large-scale systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Approaches to Dispersing Medical Biofilms (2017)

Biofilm-associated infections pose a complex problem to the medical community, in that residence within the protection of a biofilm affords pathogens greatly increased tolerances to antibiotics and antimicrobials, as well as protection from the host immune response. This results in highly recalcitrant, chronic infections and high rates of morbidity and mortality. Since as much as 80% of human bacterial infections are biofilm-associated, many researchers have begun investigating therapies that specifically target the biofilm architecture, thereby dispersing the microbial cells into their more vulnerable, planktonic mode of life. This review addresses the current state of research into medical biofilm dispersal. We focus on three major classes of dispersal agents: enzymes (including proteases, deoxyribonucleases, and glycoside hydrolases), antibiofilm peptides, and dispersal molecules (including dispersal signals, anti-matrix molecules, and sequestration molecules). Throughout our discussion, we provide detailed lists and summaries of some of the most prominent and extensively researched dispersal agents that have shown promise against the biofilms of clinically relevant pathogens, and we catalog which specific microorganisms they have been shown to be effective against. Lastly, we discuss some of the main hurdles to development of biofilm dispersal agents, and contemplate what needs to be done to overcome them.
Comparative teratological investigation of compounds structurally and pharmacologically related to thalidomide. (1981)

Compounds differing from thalidomide in either the phthalimide or the 2,6-dioxopiperidine moiety of the molecule were synthetized and tested for teratogenic potency in White New Zealand rabbits. Both the 2,6-dioxopiperidine and 2-oxopiperidine derivatives of phthalimide and phthalimidine were found to be highly teratogenic. A somewhat higher teratogenic potential appeared to be associated with the 2,6-dioxopiperidine derivatives. The most potent teratogen investigated was clearly 3-(1,3-dihydro-1-oxo2H-isoindol-2-yl)-2,6-dioxopiperidine (EM12). Compounds in which the phthalimide ring was replaced by 2,3-dihydro-1,1-dioxido-3-oxo-1,2-benzisothiazol, did not induce any embryopathic effect differing from control data. No consistent correlation between teratogenic activity and sedative properties of the compounds was detected. The results are discussed in respect to current views of the molecular mechanism leading to thalidomide embryopathy.
Fanconi Anemia Repair Pathway Dysfunction, a Potential Therapeutic Target in Lung Cancer (2014)

The Fanconi anemia (FA) pathway is a major mechanism of homologous recombination DNA repair. The functional readout of the pathway is activation through mono-ubiquitination of FANCD2 leading to nuclear foci of repair. We have recently developed an FA triple-staining immunofluorescence based method (FATSI) to evaluate FANCD2 foci formation in formalin fixed paraffin-embedded (FFPE) tumor samples. DNA-repair deficiencies have been considered of interest in lung cancer prevention, given the persistence of damage produced by cigarette smoke in this setting, as well as in treatment, given potential increased efficacy of DNA-damaging drugs. We screened 139 non-small cell lung cancer (NSCLC) FFPE tumors for FANCD2 foci formation by FATSI analysis. Among 104 evaluable tumors, 23 (22%) were FANCD2 foci negative, thus repair deficient. To evaluate and compare novel-targeted agents in the background of FA deficiency, we utilized RNAi technology to render several lung cancer cell lines FANCD2 deficient. Successful FANCD2 knockdown was confirmed by reduction in the FANCD2 protein. Subsequently, we treated the FA defective H1299D2-down and A549D2-down NSCLC cells and their FA competent counterparts (empty vector controls) with the PARP inhibitors veliparib (ABT-888) (5 μM) and BMN673 (0.5 μM), as well as the CHK1 inhibitor Arry-575 at a dose of 0.5 μM. We also treated the FA defective small cell lung cancer cell lines H719D2-down and H792D2-down and their controls with the BCL-2/XL inhibitor ABT-263 at a dose of 2 μM. The treated cells were harvested at 24, 48, and 72 h post treatment. MTT cell viability analysis showed that each agent was more cytotoxic to the FANCD2 knock-down cells. In all tests, the FA defective lung cancer cells had less viable cells as comparing to controls 72 h post treatment. Both MTT and clonogenic analyses comparing the two PARP inhibitors, showed that BMN673 was more potent compared to veliparib. Given that FA pathway plays essential roles in response to DNA damage, our results suggest that a subset of lung cancer patients are likely to be more susceptible to DNA cross-link based therapy, or to treatments in which additional repair mechanisms are targeted. These subjects can be identified through FATSI analysis. Clinical trials to evaluate this therapeutic concept are needed.
Path specification and path coherence (1982)

This paper presents an interactive method for specifying a path in space and time through a three-dimensional environment. A sequence is generated by showing the series of views along the path. The sequence is previewed on a vector scope, and after it is interactively refined, each frame is rendered on a raster device. The path is represented by a B-spline to provide smooth, continuous motion. The timing along the path is also defined by a B-spline so that changes in velocity are smooth. The use of “path coherence” is introduced. The utilization of the available data from the a priori temporal and spatial path definition holds great promise for frame to frame coherence. The path coherence can be used to reduce the number of polygons which need to be considered in a viewed environment. This reduction makes the previewing of complex environments appear less cluttered. Furthermore, the computational expense of the culling and sorting operations in the visible line/surface determination is reduced. One sample usage of this is a tree-structured partitioned environment where the priority ordering of the environment must be changed only when the path crosses a partition boundary.
Tunable Hydrogels for External Manipulation of Cellular Microenvironments through Controlled Photodegradation (2009)

A photocleavable, poly(ethylene-glycol)-based hydrogel is presented in which predictable, user-defined gradients in the network's structure can be fabricated in real time under cytocompatible conditions. This platform provides new opportunities to investigate how material structure influences cell function. Here, cell morphology is directed spatially by degradation-induced gradients in the local polymer density (see figure, scale bars: 50 μm). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Viral Evolution as a Tool to Improve the Tetracycline-regulated Gene Expression System (2004)

We present viral evolution as a novel and powerful method to optimize non-viral proteins. We used this approach to optimize the tetracycline (Tc)-regulated gene expression system (Tet system) for its function in mammalian cells. The components of the Tet system were incorporated in the human immunodeficiency virus (HIV)-1 virus such that viral replication is controlled by this regulatory system. Upon long term replication of this HIV-rtTA virus in human T cells, we obtained a virus variant with an enhanced replication potential resulting from an improved rtTA component of the introduced Tet system. We identified a single amino acid exchange, F86Y, which enhances the transcriptional activity and doxycycline (dox) sensitivity of rtTA. We generated a new rtTA variant that is 5-fold more active at high dox levels than the initial rtTA, and 25-fold more sensitive to dox, whereas the background activity in the absence of dox is not increased. This new rtTA variant will be very useful in biological applications that require a more sensitive or active Tet system. Our results demonstrate that the viral evolution strategy can be used to improve the activity of genes by making them an integral and essential part of the virus.
REGULATION OF THE EXPRESSION OF LIPOGENIC ENZYME GENES BY CARBOHYDRATE (1997)

Diets high in simple carbohydrates and low in fats lead in the mammalian liver to induction of a set of enzymes involved in lipogenesis. This induction occurs, in part, through transcriptional mechanisms that lead to elevated levels of the mRNA for these enzymes. For most of the lipogenic enzymes, an increase in glucose metabolism is required to trigger the transcriptional response. The intracellular mediator of this signaling pathway is unknown, although evidence suggests either glucose-6-phosphate or xylulose-5-phosphate. Studies to map the regulatory sequences of lipogenic enzyme genes involved in the transcriptional response have been performed for the L-type pyruvate kinase, S14, and acetyl-coenzyme A carboxylase genes. These studies have identified the DNA sequences necessary to link the signal generated by carbohydrate metabolism to specific nuclear transcription factors.
Biological formation of caproate and caprylate from acetate: fuel and chemical production from low grade biomass (2010)

This research introduces an alternative mixed culture fermentation technology for anaerobic digestion to recover valuable products from low grade biomass. In this mixed culture fermentation, organic waste streams are converted to caproate and caprylate as precursors for biodiesel or chemicals. It was found that acetate, as the main intermediate of anaerobic digestion, can be elongated to medium chain fatty acids with six and eight carbon atoms. Mixed microbial communities were able to produce 8.17 g l−1 caproate and 0.32 g l−1 caprylate under methanogenesis-suppressed conditions in a stable batch reactor run. The highest production rate was 25.6 mM C caproate per day with a product yield of 0.6 mol C per mol C. This elongation process occurred with both ethanol and hydrogen as electron donors, demonstrating the flexibility of the process. Microbial characterization revealed that the microbial populations were stable and dominated by relatives of Clostridium kluyveri.
NMR Spectroscopic Analysis of the First Two Steps of the Pentose-Phosphate Pathway Elucidates the Role of 6-Phosphogluconolactonase (2001)

The pentose-phosphate pathway provides reductive power and nucleotide precursors to the cell through oxidative and nonoxidative branches, respectively. 6-Phosphogluconolactonase is the second enzyme of the oxidative branch and catalyzes the hydrolysis of 6-phosphogluconolactones, the products of glucose 6-phosphate oxidation by glucose-6-phosphate dehydrogenase. The role of 6-phosphogluconolactonase was still questionable, because 6-phosphogluconolactones were believed to undergo rapid spontaneous hydrolysis. In this work, nuclear magnetic resonance spectroscopy was used to characterize the chemical scheme and kinetic features of the oxidative branch. We show that 6-phosphogluconolactones have in fact a nonnegligible lifetime and are highly electrophilic compounds. The delta form (1-5) of the lactone is the only product of glucose 6-phosphate oxidation. Subsequently, it leads to the gamma form (1-4) by intramolecular rearrangement. However, only the delta form undergoes spontaneous hydrolysis, the gamma form being a "dead end" of this branch. The delta form is the only substrate for 6-phosphogluconolactonase. Therefore, 6-phosphogluconolactonase activity accelerates hydrolysis of the delta form, thus preventing its conversion into the gamma form. Furthermore, 6-phosphogluconolactonase guards against the accumulation of delta-6-phosphogluconolactone, which may be toxic through its reaction with endogenous cellular nucleophiles. Finally, the difference between activity of human, Trypanosoma brucei, and Plasmodium falciparum 6-phosphogluconolactonases is reported and discussed.
Transient expression of a tumor-specific single-chain fragment and a chimeric antibody in tobacco leaves (1999)

To evaluate the expression of different forms of a tumor-specific antibody in plants, we adapted a recently described Agrobacterium-mediated transient expression system. A recombinant single-chain Fv antibody (scFvT84.66) and a full-size mouse/human chimeric antibody (cT84.66) derived from the parental murine mAb T84. 66 specific for the human carcinoembryonic antigen were engineered into a plant expression vector. Chimeric T84.66 heavy and light chain genes were constructed by exchanging the mouse light and heavy chain constant domain sequences with their human counterparts and cloned into two independent plant expression vectors. In vivo assembly of full-size cT84.66 was achieved by simultaneous expression of the light and heavy chains after vacuum infiltration of tobacco leaves with two populations of recombinant Agrobacterium. Upscaling the transient system permitted purification of functional recombinant antibodies from tobacco leaf extracts within a week. His6-tagged scFvT84.66 was purified by immobilized metal affinity chromatography and cT84.66 by protein A affinity chromatography. Sufficient amounts of recombinant antibodies were recovered for detailed characterization by SDS/PAGE, Western blotting, and ELISA.
L1 neural cell adhesion molecule is a survival factor for fetal dopaminergic neurons (1998)

Cell adhesion molecules play a central role in neural development and are also critically involved in axonal regeneration and synaptic plasticity in the adult nervous system. We investigated whether the neural cell adhesion molecule L1 was capable of stimulating survival and differentiation in the mid-brain dopaminergic neurons which degenerate in Parkinson's disease. Monoclonal L1 antibodies, known to enhance neurite outgrowth, were substrate-coated or added at the time of plating to medium of cultures containing mid-brain dopaminergic neurons from 14-day-old fetal rats. Tritiated dopamine uptake per well and the number of tyrosine hydroxylase-immunopositive neurons increased in a dose-dependent manner with increasing concentrations of L1 antibody, suggesting that L1 acts directly or indirectly as a growth factor for dopaminergic neurons. A monoclonal L1 antibody not enhancing neurite outgrowth was ineffective. The growth-promoting effects of L1 antibodies on dopaminergic neurons in culture did not appear to be mediated by the cAMP-activated protein kinase A pathway, since combined treatment with a phosphodiesterase inhibitor had only additive effects on the L1-induced increase of dopamine uptake, and in addition, antibodies against L1 failed to protect cultures of dopaminergic neurons against the neurotoxin MPP+, whereas pretreatment with forskolin and phosphodiesterase type-IV inhibitors was strongly protective.