gebhart/patrepeval huggingface dataset:
The Beta-Glucan Receptor Dectin-1 Recognizes Specific Morphologies of Aspergillus fumigatus (2005)

Alveolar macrophages represent a first-line innate host defense mechanism for clearing inhaled Aspergillus fumigatus from the lungs, yet contradictory data exist as to which alveolar macrophage recognition receptor is critical for innate immunity to A. fumigatus. Acknowledging that the A. fumigatus cell wall contains a high beta-1,3-glucan content, we questioned whether the beta-glucan receptor dectin-1 played a role in this recognition process. Monoclonal antibody, soluble receptor, and competitive carbohydrate blockage indicated that the alveolar macrophage inflammatory response, specifically the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1alpha (IL-1alpha), IL-1beta, IL-6, CXCL2/macrophage inflammatory protein-2 (MIP-2), CCL3/macrophage inflammatory protein-1alpha (MIP-1alpha), granulocyte-colony stimulating factor (G-CSF), and granulocyte monocyte-CSF (GM-CSF), to live A. fumigatus was dependent on recognition via the beta-glucan receptor dectin-1. The inflammatory response was triggered at the highest level by A. fumigatus swollen conidia and early germlings and correlated to the levels of surface-exposed beta glucans, indicating that dectin-1 preferentially recognizes specific morphological forms of A. fumigatus. Intratracheal administration of A. fumigatus conidia to mice in the presence of a soluble dectin-Fc fusion protein reduced both lung proinflammatory cytokine/chemokine levels and cellular recruitment while modestly increasing the A. fumigatus fungal burden, illustrating the importance of beta-glucan-initiated dectin-1 signaling in defense against this pathogen. Collectively, these data show that dectin-1 is centrally required for the generation of alveolar macrophage proinflammatory responses to A. fumigatus and to our knowledge provides the first in vivo evidence for the role of dectin-1 in fungal innate defense.
Functional Characterization of Human Receptors for Short Chain Fatty Acids and Their Role in Polymorphonuclear Cell Activation (2003)

Short chain fatty acids (SCFAs), including acetate, propionate, and butyrate, are produced at high concentration by bacteria in the gut and subsequently released in the bloodstream. Basal acetate concentrations in the blood (about 100 microm) can further increase to millimolar concentrations following alcohol intake. It was known previously that SCFAs can activate leukocytes, particularly neutrophils. In the present work, we have identified two previously orphan G protein-coupled receptors, GPR41 and GPR43, as receptors for SCFAs. Propionate was the most potent agonist for both GPR41 and GPR43. Acetate was more selective for GPR43, whereas butyrate and isobutyrate were more active on GPR41. The two receptors were coupled to inositol 1,4,5-trisphosphate formation, intracellular Ca2+ release, ERK1/2 activation, and inhibition of cAMP accumulation. They exhibited, however, a differential coupling to G proteins; GPR41 coupled exclusively though the Pertussis toxin-sensitive Gi/o family, whereas GPR43 displayed a dual coupling through Gi/o and Pertussis toxin-insensitive Gq protein families. The broad expression profile of GPR41 in a number of tissues does not allow us to infer clear hypotheses regarding its biological functions. In contrast, the highly selective expression of GPR43 in leukocytes, particularly polymorphonuclear cells, suggests a role in the recruitment of these cell populations toward sites of bacterial infection. The pharmacology of GPR43 matches indeed the effects of SCFAs on neutrophils, in terms of intracellular Ca2+ release and chemotaxis. Such a neutrophil-specific SCFA receptor is potentially involved in the development of a variety of diseases characterized by either excessive or inefficient neutrophil recruitment and activation, such as inflammatory bowel diseases or alcoholism-associated immune depression. GPR43 might therefore constitute a target allowing us to modulate immune responses in these pathological situations.
Randomized BioBrick Assembly: A Novel DNA Assembly Method for Randomizing and Optimizing Genetic Circuits and Metabolic Pathways (2013)

The optimization of genetic circuits and metabolic pathways often involves constructing various iterations of the same construct or using directed evolution to achieve the desired function. Alternatively, a method that randomizes individual parts in the same assembly reaction could be used for optimization by allowing for the ability to screen large numbers of individual clones expressing randomized circuits or pathways for optimal function. Here we describe a new assembly method to randomize genetic circuits and metabolic pathways from modular DNA fragments derived from PCR-amplified BioBricks. As a proof-of-principle for this method, we successfully assembled CMY (Cyan-Magenta-Yellow) three-gene circuits using Gibson Assembly that express CFP, RFP, and YFP with independently randomized promoters, ribosome binding sites, transcriptional terminators, and all parts randomized simultaneously. Sequencing results from 24 CMY circuits with various parts randomized show that 20/24 circuits are distinct and expression varies over a 200-fold range above background levels. We then adapted this method to randomize the same parts with enzyme coding sequences from the lycopene biosynthesis pathway instead of fluorescent proteins, designed to independently express each enzyme in the pathway from a different promoter. Lycopene production is improved using this randomization method by about 30% relative to the highest polycistronic-expressing pathway. These results demonstrate the potential of generating nearly 20,000 unique circuit or pathway combinations when three parts are permutated at each position in a three-gene circuit or pathway, and the methodology can likely be adapted to other circuits and pathways to maximize products of interest.
Wavelength bistability based on optical injection in a novel tunable dual mode laser (2016)

A novel tunable dual mode laser is proposed based on a double-layer Bragg grating structure, named double-layer grating distributed Bragg reflector (DLG-DBR) laser. With controlling the gain saturation condition, different oscillating states can be observed. The nonlinear dynamics characteristics including bifurcation of the laser under optical injection with two different start-up sequences are analyzed with numerical simulations. Furthermore, we investigate the lasing wavelength bistability of the laser combined with its tuning characteristics theoretically. Optical memory operation based on the external optical injection locking bistability of the dual mode device is proposed. The memory operation can be achieved in the whole wavelength window with a 10 nm tuning range. A mode suppression ratio (MSR) of more than 45 dB is achieved between the two bistable states.
Oral GPIIb / IIIa Antagonists: What Went Wrong? (2004)

GPIIb/IIIa receptor antagonists block fibrinogen binding to platelets and as a result inhibit platelet aggregation. They are very potent inhibitors due to the critical role fibrinogen binding plays in platelet aggregation. When given intravenously these drugs have been shown to be very effective as adjuvant therapy in percutaneous coronary intervention and in acute coronary syndromes. However, despite being as potent as their intravenous counterparts, all of the oral inhibitors showed no benefit or even increased mortality in clinical trials. There are a number of reasons for their failure. The target was different, chronic treatment to prevent thrombotic events as opposed to short-term treatment to prevent acute events and as a result, different dosing regimens were used. The acute use aims for a high level of inhibition (80-90%) while the chronic use produced lower levels of inhibition. Many of the oral inhibitors had low bioavailability that led to a large peak-trough difference. Most GPIIb/IIIa antagonists have the ability to activate platelets through a GPIIb/IIIa-mediated process. This is known as partial agonism. In the presence of high drug levels, such as during an infusion this is not a problem, however combined with the low trough levels with oral inhibitors this can lead to an increase in platelet aggregation. Other problems include drug-induced conformational changes in GPIIb/IIIa (ligand-regulated binding sites) and possible pharmacogenomics effects in the response to the drugs, in particular the Pl(A) polymorphism in GPIIb/IIIa. By addressing these issues it is possible for a new generation of oral GPIIb/IIIa antagonist to be developed.
Carboxylation of Terminal Alkynes with Carbon Dioxide Catalyzed by Poly(N‐Heterocyclic Carbene)‐Supported Silver Nanoparticles (2012)

Abstract An N‐heterocyclic carbene (NHC) polymer supported silver nanoparticle catalyst system was developed. The novel nano‐composite catalyst demonstrated very high activity and excellent stability and reusability in the carboxylation of terminal alkynes with carbon dioxide at ambient conditions. The unique N‐heterocyclic carbene polymer and silver nanoparticle composite structure provided a synergistic effect on activation of terminal alkynes and carbon dioxide that contributed to the high catalytic activity. The poly‐NHC‐silver catalyst exhibited excellent substrate generality and tolerance to various functionalities. In addition, the catalyst is stable to air and moisture and can be easily recovered and reused.
Yeast artificial chromosome contigs reveal that distal variable-region genes reside at least 3 megabases from the joining regions in the murine immunoglobulin kappa locus. (1995)

The immunoglobulin kappa gene locus encodes 95% of the light chains of murine antibody molecules and is thought to contain up to 300 variable (V kappa)-region genes generally considered to comprise 20 families. To delineate the locus we have isolated 29 yeast artificial chromosome genomic clones that form two contigs, span > 3.5 megabases, and contain two known non-immunoglobulin kappa markers. Using PCR primers specific for 19 V kappa gene families and Southern analysis, we have refined the genetically defined order of these V kappa gene families. Of these, V kappa 2 maps at least 3.0 Mb from the joining (J kappa) region and appears to be the most distal V kappa gene segment.
La senda del jaguar (2009)

La perdida de habitat esta poniendo en peligro al gran felino de America, al dejarlo aislado en areas fragmentarias. Un proyecto multinacional se propone crear una vasta red de corredores que conecten las poblaciones de 18 paises, desde Mexico hasta Argentina.
Persistent Pain as a Disease Entity: Implications for Clinical Management (2004)

Pain has often been regarded merely as a symptom that serves as a passive warning signal of an underlying disease process. Using this model, the goal of treatment has been to identify and address the pathology causing pain in the expectation that this would lead to its resolution. However, there is accumulating evidence to indicate that persistent pain cannot be regarded as a passive symptom. Continuing nociceptive inputs result in a multitude of consequences that impact on the individual, ranging from changes in receptor function to mood dysfunction, inappropriate cognitions, and social disruption. These changes that occur as a consequence of continuing nociceptive inputs argue for the consideration of persistent pain as a disease entity in its own right. As with any disease, the extent of these changes is largely determined by the internal and external environments in which they occur. Thus genetic, psychological and social factors may all contribute to the perception and expression of persistent pain. Optimal outcomes in the management of persistent pain may be achieved not simply by attempting to remove the cause of the pain, but by addressing both the consequences and contributors that together comprise the disease of persistent pain.
Expression of Dicer and Drosha in triple-negative breast cancer (2012)

These findings indicate that Dicer and Drosha expression is deregulated in triple-negative breast cancers.
An approach to interpreting spirometry. (2004)

Spirometry is a powerful tool that can be used to detect, follow, and manage patients with lung disorders. Technology advancements have made spirometry much more reliable and relatively simple to incorporate into a routine office visit. However, interpreting spirometry results can be challenging because the quality of the test is largely dependent on patient effort and cooperation, and the interpreter's knowledge of appropriate reference values. A simplified and stepwise method is key to interpreting spirometry. The first step is determining the validity of the test. Next, the determination of an obstructive or restrictive ventilatory patten is made. If a ventilatory pattern is identified, its severity is graded. In some patients, additional tests such as static lung volumes, diffusing capacity of the lung for carbon monoxide, and bronchodilator challenge testing are needed. These tests can further define lung processes but require more sophisticated equipment and expertise available only in a pulmonary function laboratory.
Efficient polymer white-light-emitting diodes with a phosphorescent dopant (2006)

Efficient polymer white-light-emitting diodes (WPLEDs) with an active polymer layer have been demonstrated. The white emission consists of two emission bands in the blue and yellow ranges. The blue polymer is a host (PFO) and the yellow dopant is a phosphorescent dye of Ir(CzBPPF)2(PZ), i.e. Iridium(III) bis(2,4-diflurophenyl-2-pyridine-4-phenyl-p-carbarzole)(2-(4H-1,2,4-triazol-3-yl)-pyridine). When the doping concentration of Ir(CzBPPF)2(PZ) is 2 wt%, pure white light is obtained, which possesses stable white light CIE coordinates, efficiency of 5.6 cd A−1 (9.5 V) and luminance of 7656 cd m−2 (14 V). The EL process in the device was proved mainly to be the charge trap mechanism.
The interphase thickness of linear polyethylene (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe interphase thickness of linear polyethyleneLeo Mandelkern, R. G. Alamo, and M. A. KennedyCite this: Macromolecules 1990, 23, 21, 4721–4723Publication Date (Print):October 1, 1990Publication History Published online1 May 2002Published inissue 1 October 1990https://pubs.acs.org/doi/10.1021/ma00223a034https://doi.org/10.1021/ma00223a034research-articleACS PublicationsRequest reuse permissionsArticle Views393Altmetric-Citations77LEARN 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
Tauopathies with parkinsonism: clinical spectrum, neuropathologic basis, biological markers, and treatment options (2009)

Tauopathies with parkinsonism represent a spectrum of disease entities unified by the pathologic accumulation of hyperphosphorylated tau protein fragments within the central nervous system. These pathologic characteristics suggest shared pathogenetic pathways and possible molecular targets for disease-modifying therapeutic interventions. Natural history studies, for instance, in progressive supranuclear palsy, frontotemporal dementia with parkinsonism linked to chromosome 17, corticobasal degeneration, and Niemann-Pick disease type C as well as in amyotrophic lateral sclerosis/Parkinson-dementia complex permit clinical characterization of the disease phenotypes and are crucial to the development and validation of biological markers for differential diagnostics and disease monitoring, for example, by use of neuroimaging or proteomic approaches. The wide pathologic and clinical spectrum of the tauopathies with parkinsonism is reviewed in this article, and perspectives on future advances in the understanding of the pathogenesis are given, together with potential therapeutic strategies.
Dietary supplementation with fish oil rich in omega-3 polyunsaturated fatty acids in children with bronchial asthma (2000)

Omega-3 polyunsaturated fatty acids have anti-inflammatory effects in vitro, and high dietary levels are associated with a lower incidence of inflammatory diseases. However, only limited effects have been demonstrated in asthma. The effects of dietary supplementation with fish oil for 10 months in 29 children with bronchial asthma was investigated in a randomized controlled fashion. In order to minimize the effects of environmental inhaled allergens and diet, this study was performed in a long-term treatment hospital. Subjects received fish oil capsules containing 84 mg eicosapentaenoic acid (EPA) and 36 mg docosahexaenoic acid (DHA) or control capsules containing 300 mg olive oil. The daily dosages of EPA and DHA were 17.0-26.8 and 7.3-11.5 mg x kg body weight(-1), respectively. Asthma symptom scores decreased and responsiveness to acetylcholine decreased in the fish oil group but not in the control group. In addition, plasma EPA levels increased significantly only in the fish oil group (p<0.0088). No significant side-effects were observed. The present results suggest that dietary supplementation with fish oil rich in the omega-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid is beneficial for children with bronchial asthma in a strictly controlled environment in terms of inhalant allergens and diet.
Acyl carrier protein import into chloroplasts. Both the precursor and mature forms are substrates for phosphopantetheine attachment by a soluble chloroplast holo-acyl carrier protein synthase. (1991)

Recently a chloroplast holo-acyl carrier protein (holoACP) synthase activity was identified which attached the phosphopantetheine prosthetic group to acyl carrier protein, producing holoACP (Fernandez and Lamppa (1990) Plant Cell 2, 195-206). Here we show that the mature form of ACP (apoACP), after entry into the chloroplast and removal of the transit peptide, is a substrate for modification by the holoACP synthase. Modification occurs optimally at 37 degrees C and is inhibited by 5 mM 3',5'-ADP and 2 mM EDTA. An ACP construct (matACP) lacking the transit peptide was also converted to the holoACP form in an organelle-free assay, independent of precursor cleavage. The matACP construct was used to monitor the chromatographic separation of the holoACP synthase from the transit peptidase. Superose 12 gel filtration analysis indicates that the holoACP synthase has an apparent Mr of approximately 50,000. Using fractions enriched for the holoACP synthase it was demonstrated that the precursor of ACP is also modified in the presence of CoA and subsequently can be proteolytically processed directly to holoACP. Kinetic analysis, however, indicates that removal of the transit peptide is a much faster reaction than phosphopantetheine addition, suggesting that apoACP is the primary substrate for the chloroplast holoACP synthase in vivo.
Quantum Mechanical Continuum Solvation Models (2005)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTQuantum Mechanical Continuum Solvation ModelsJacopo Tomasi, Benedetta Mennucci, and Roberto CammiView Author Information Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via Risorgimento 35, 56126 Pisa, Italy, and Dipartimento di Chimica, Università di Parma, Viale delle Scienze 17/A, 43100 Parma, Italy Cite this: Chem. Rev. 2005, 105, 8, 2999–3094Publication Date (Web):July 26, 2005Publication History Received6 January 2005Published online26 July 2005Published inissue 1 August 2005https://pubs.acs.org/doi/10.1021/cr9904009https://doi.org/10.1021/cr9904009research-articleACS PublicationsCopyright © 2005 American Chemical SocietyRequest reuse permissionsArticle Views40539Altmetric-Citations13824LEARN 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 SUBJECTS:Cavities,Molecules,Solution chemistry,Solvation,Solvents Get e-Alerts
Discovery of a First-in-Class Receptor Interacting Protein 1 (RIP1) Kinase Specific Clinical Candidate (GSK2982772) for the Treatment of Inflammatory Diseases (2017)

RIP1 regulates necroptosis and inflammation and may play an important role in contributing to a variety of human pathologies, including immune-mediated inflammatory diseases. Small-molecule inhibitors of RIP1 kinase that are suitable for advancement into the clinic have yet to be described. Herein, we report our lead optimization of a benzoxazepinone hit from a DNA-encoded library and the discovery and profile of clinical candidate GSK2982772 (compound 5), currently in phase 2a clinical studies for psoriasis, rheumatoid arthritis, and ulcerative colitis. Compound 5 potently binds to RIP1 with exquisite kinase specificity and has excellent activity in blocking many TNF-dependent cellular responses. Highlighting its potential as a novel anti-inflammatory agent, the inhibitor was also able to reduce spontaneous production of cytokines from human ulcerative colitis explants. The highly favorable physicochemical and ADMET properties of 5, combined with high potency, led to a predicted low oral dose in humans.