gebhart/patrepeval huggingface dataset:
Neurotensin activation of the NTR1 on spinally-projecting serotonergic neurons in the rostral ventromedial medulla is antinociceptive (2005)

Microinjection of neurotensin (NT) in the rostral ventromedial medulla (RVM) produces dose-dependent antinociception. The NTR1 (Neurotensin Receptor Subtype 1) may mediate part of this response, however definitive evidence is lacking, and the spinal mediators of NTR1-induced antinociception are unknown. In the present study, we used immunohistochemical techniques to show that the NTR1, but not the NTR2 is expressed by spinally projecting serotonergic neurons of the RVM. We also show that microinjection of NT or the NTR1-selective agonist PD149163 in the RVM both produce dose-dependent antinociception in the tail-flick test that is blocked by the NTR1-selective antagonist SR48692. The antinociception produced by NT or PD149163 is also blocked by intrathecal administration of the non-selective serotonergic receptor antagonist methysergide. The results of these experiments provide anatomical and behavioral evidence that activation of NTR1-expressing spinally projecting neurons in the RVM produces antinociception through release of serotonin in the spinal dorsal horn. These results support the conclusion that the NTR1 plays an important role in the central modulation of nociception.
Dectin-1 Regulates Hepatic Fibrosis and Hepatocarcinogenesis by Suppressing TLR4 Signaling Pathways (2015)

Dectin-1 is a C-type lectin receptor critical in anti-fungal immunity, but Dectin-1 has not been linked to regulation of sterile inflammation or oncogenesis. We found that Dectin-1 expression is upregulated in hepatic fibrosis and liver cancer. However, Dectin-1 deletion exacerbates liver fibro-inflammatory disease and accelerates hepatocarcinogenesis. Mechanistically, we found that Dectin-1 protects against chronic liver disease by suppressing TLR4 signaling in hepatic inflammatory and stellate cells. Accordingly, Dectin-1(-/-) mice exhibited augmented cytokine production and reduced survival in lipopolysaccharide (LPS)-mediated sepsis, whereas Dectin-1 activation was protective. We showed that Dectin-1 inhibits TLR4 signaling by mitigating TLR4 and CD14 expression, which are regulated by Dectin-1-dependent macrophage colony stimulating factor (M-CSF) expression. Our study suggests that Dectin-1 is an attractive target for experimental therapeutics in hepatic fibrosis and neoplastic transformation. More broadly, our work deciphers critical cross-talk between pattern recognition receptors and implicates a role for Dectin-1 in suppression of sterile inflammation, inflammation-induced oncogenesis, and LPS-mediated sepsis.
Change of bacterial communities in sediments along Songhua River in Northeastern China after a nitrobenzene pollution event (2008)

More than 100 tons of nitrobenzene and related compounds were released into Songhua River due to the explosion of an aniline production factory in November, 2005. Sediment samples were taken from the heavily polluted drainage canal, one upstream and three downstream river sites. The change of bacterial community structures along the river was studied by denaturing gradient gel electrophoresis (DGGE) and cloning and sequencing of 16S rRNA genes with five clone libraries constructed and 101 sequences acquired representing 172 clones. Both DGGE profiles and sequences of 16S rRNA genes from clone libraries demonstrated that the contaminated drainage canal and three downstream river sites were similar in that all had Betaproteobacteria, mainly grouped into Comamonadaceae, as the dominant group of bacteria, and all had Firmicutes, primarily as Clostridium spp. These results suggest that these latter two groups of bacteria may play potential roles in degradation and detoxification of nitrobenzene in the present contaminated river environments.
Rat liver aromatic L-amino acid decarboxylase: Spectroscopic and kinetic analysis of the coenzyme and reaction intermediates (1993)

The physiochemical properties of the coenzyme in rat liver aromatic L-amino acid decarboxylase (AADC) expressed in Escherichia coli have been studied by spectroscopic analysis of the enzyme, its reaction intermediates, and its complexes with substrate analogs. The enzyme, having one pyridoxal 5'-phosphate (PLP) per subunit, shows a prominent absorption maximum at 335 nm and a weaker one at 425 nm. The spectrum did not essentially change in the pH range of 6.0-8.0. When the coenzyme was excited at 335 nm, it emitted fluorescence primarily at 520 nm. The structure for the absorption at 335 nm was ascribed to the enolimine form of the PLP-lysine Schiff base. On the reaction of AADC with L-3,4-dihydroxyphenylalanine (L-dopa), the absorption of PLP showed biphasic changes before reaching a steady-state. Results of both pre-steady-state and steady-state kinetic analyses were consistent with the model that the reaction proceeds as shown in the equation: E + S<==>X1<==>X2-->E + P. The rate constant was determined for each step, and the Km value for L-dopa was obtained as 0.086 mM. The absorption spectra of the two intermediates, X1 and X2, were postulated from the calculation of the absorption changes during the first and the second steps of the reaction in which X1 and X2 showed an absorption maximum at 425 and 380 nm, respectively, with a concomitant decrease in absorbance at 335 nm. These predicted absorption spectra of X1 and X2 showed striking resemblances to those of AADC complexed with dihydroxyphenylacetic acid (DOPAc) and L-dopa methyl ester (DopaOMe), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Nucleosides. I. 5'-Amino-5'-deoxyuridine and 5'-Amino-5'-deoxythymidine1a,b (1962)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNucleosides. I. 5'-Amino-5'-deoxyuridine and 5'-Amino-5'-deoxythymidine1a,bJerome P. Horwitz, Arthur J. Tomson, Joyce A. Urbanski, and Jonathan ChuaCite this: J. Org. Chem. 1962, 27, 9, 3045–3048Publication Date (Print):September 1, 1962Publication History Published online1 May 2002Published inissue 1 September 1962https://doi.org/10.1021/jo01056a013RIGHTS & PERMISSIONSArticle Views393Altmetric-Citations74LEARN 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 InReddit PDF (480 KB) Get e-Alerts Get e-Alerts
Ultrafast Probing and Control of Molecular Dynamics: Beyond the Pump‐Probe Method (2001)

Introduction Four-Wave Mixing Techniques Differences Between the Pump-Probe Method and Four-Wave Mixing Off-Resonance FWM On-Resonance FWM Controlling Ground or Excited-State Observation Inhomogeneous Broadening and Photon-Echo Measurements Experimental Methods Results Off-Resonance Measurements Resonance Measurements Coherent Control with FWM Discussion Off-Resonance FWM and Time-Resolved Measurements of Ground-State Dynamics Resonance FWM, Ground and Excited-State Dynamics
Human IgG1 antibodies suppress angiogenesis in a target-independent manner (2016)

Aberrant angiogenesis is implicated in diseases affecting nearly 10% of the world's population. The most widely used anti-angiogenic drug is bevacizumab, a humanized IgG1 monoclonal antibody that targets human VEGFA. Although bevacizumab does not recognize mouse Vegfa, it inhibits angiogenesis in mice. Here we show bevacizumab suppressed angiogenesis in three mouse models not via Vegfa blockade but rather Fc-mediated signaling through FcγRI (CD64) and c-Cbl, impairing macrophage migration. Other approved humanized or human IgG1 antibodies without mouse targets (adalimumab, alemtuzumab, ofatumumab, omalizumab, palivizumab and tocilizumab), mouse IgG2a, and overexpression of human IgG1-Fc or mouse IgG2a-Fc, also inhibited angiogenesis in wild-type and FcγR humanized mice. This anti-angiogenic effect was abolished by Fcgr1 ablation or knockdown, Fc cleavage, IgG-Fc inhibition, disruption of Fc-FcγR interaction, or elimination of FcRγ-initated signaling. Furthermore, bevacizumab's Fc region potentiated its anti-angiogenic activity in humanized VEGFA mice. Finally, mice deficient in FcγRI exhibited increased developmental and pathological angiogenesis. These findings reveal an unexpected anti-angiogenic function for FcγRI and a potentially concerning off-target effect of hIgG1 therapies.
A neutron diffraction study of 2,6-diaminopyridine at 20 K (1987)

C 5 NH 3 (NH 2 ) 2 cristallise dans le systeme orthorhombique avec le groupe d'espace P2 1 2 1 2 1 . Affinement de la structure jusqu'a 0,093
Tyrosine 112 of Latent Membrane Protein 2A Is Essential for Protein Tyrosine Kinase Loading and Regulation of Epstein-Barr Virus Latency (1998)

Latent membrane protein 2A (LMP2A) of Epstein-Barr virus (EBV) is expressed on the plasma membrane of B lymphocytes latently infected with EBV and blocks B-cell receptor (BCR) signal transduction in EBV-immortalized B cells in vitro. The LMP2A amino-terminal domain that is essential for the LMP2A-mediated block on BCR signal transduction contains eight tyrosine residues. Association of Syk protein tyrosine kinase (PTK) with LMP2A occurs at the two tyrosines of the LMP2A immunoreceptor tyrosine-based activation motif, and it is hypothesized that Lyn PTK associates with the YEEA amino acid motif at LMP2A tyrosine 112 (Y112). To examine the specific association of Lyn PTK to LMP2A, a panel of LMP2A cDNA expression vectors containing LMP2A mutations were transfected into an EBV-negative B-cell line and analyzed for Lyn and LMP2A coimmunoprecipitation. Lyn associates with wild-type LMP2A and other LMP2A mutant constructs, but Lyn association is lost in the LMP2A construct containing a tyrosine (Y)-to-phenylalanine (F) mutation at LMP2A residue Y112 (LMP2AY112F). Next, the LMP2AY112F mutation was recombined into the EBV genome to generate stable lymphoblastoid cell lines (LCLs) transformed with the LMP2AY112F mutant virus. Analysis of BCR-mediated signal transduction in the LMP2AY112F LCLs revealed loss of the LMP2A-mediated block in BCR signal transduction. In addition, LMP2A was not tyrosine phosphorylated in LMP2AY112F LCLs. Together these data indicate the importance of the LMP2A Y112 residue in the ability of LMP2A to block BCR-mediated signal transduction and place the role of this residue and its interaction with Lyn PTK as essential to LMP2A phosphorylation, PTK loading, and down-modulation of PTKs involved in BCR-mediated signal transduction.
tRNA-Derived Fragments Target the Ribosome and Function as Regulatory Non-Coding RNA inHaloferax volcanii (2012)

Nonprotein coding RNA (ncRNA) molecules have been recognized recently as major contributors to regulatory networks in controlling gene expression in a highly efficient manner. These RNAs either originate from their individual transcription units or are processing products from longer precursor RNAs. For example, tRNA-derived fragments (tRFs) have been identified in all domains of life and represent a growing, yet functionally poorly understood, class of ncRNA candidates. Here we present evidence that tRFs from the halophilic archaeon Haloferax volcanii directly bind to ribosomes. In the presented genomic screen of the ribosome-associated RNome, a 26-residue-long fragment originating from the 5' part of valine tRNA was by far the most abundant tRF. The Val-tRF is processed in a stress-dependent manner and was found to primarily target the small ribosomal subunit in vitro and in vivo. As a consequence of ribosome binding, Val-tRF reduces protein synthesis by interfering with peptidyl transferase activity. Therefore this tRF functions as ribosome-bound small ncRNA capable of regulating gene expression in H. volcanii under environmental stress conditions probably by fine tuning the rate of protein production.
Actinide chelation: biodistribution andin vivocomplex stability of the targeted metal ions (2012)

Because of the continuing use of nuclear fuel sources and heightened threats of nuclear weapon use, the amount of produced and released radionuclides is increasing daily, as is the risk of larger human exposure to fission product actinides. A rodent model was used to follow the in vivo distribution of representative actinides, administered as free metal ions or complexed with chelating agents including diethylenetriamine pentaacetic acid (DTPA) and the hydroxypyridinonate ligands 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO). Different metabolic pathways for the different metal ions were evidenced, resulting in intricate ligand- and metal-dependent decorporation mechanisms. While the three studied chelators are known for their unrivaled actinide decorporation efficiency, the corresponding metal complexes may undergo in vivo decomposition and release metal ions in various biological pools. This study sets the basis to further explore the metabolism and in vivo coordination properties of internalized actinides for the future development of viable therapeutic chelating agents.
Wound bed score and its correlation with healing of chronic wounds (2006)

Adequate wound bed preparation is essential for healing of leg ulcers, and consists of controlling exudate and edema, decreasing the bacterial burden, promoting healthy granulation tissue, and removing necrotic tissue. Currently, there is no classification system for wound bed preparation that has predictive value. Based on past work and the authors' experience, we have now developed and tested a new classification system that scores the following parameters: healing edges (wound edge effect), presence of eschar, greatest wound depth/granulation tissue, amount of exudate amount, edema, peri-wound dermatitis, peri-wound callus and or fibrosis, and a pink/red wound bed. Each parameter receives a score from 0 (worst score) to 2 (best score), and all the parameter scores are added for a total score. Each wound can have a maximum score of 16 (the best score possible), to a minimum score of 0 (the worst score possible). We used this wound bed score (WBS) system in a study of 177 patients with venous ulcers who had been prospectively treated with and randomized to either conventional therapy (compression alone) or a living bilayered skin construct (BSC). We evaluated serial photographs at baseline to determine whether the results would be predictive of complete wound closure and could validate the WBS. We found that wounds that ultimately achieved full closure had a statistically significant higher WBS than those that did not heal (p = 0.0012). This was also true when separating wounds by treatment modality: standard therapy (p = 0.044) and treatment with a BSC (p = 0.011). When dividing the WBS in the following quartile groups: scores 4-10, 10-12, 12-13, and 13-16, the percentage of healed wounds correlated with the WBS (p = 0.0008). For all wounds, a one unit increase in total WBS resulted on average in a 22.8% increase in odds of healing (OR = 1.228). This WBS seems to have validity in predicting complete wound closure in wounds treated with either standard therapy or advanced modalities, such as BSC. If confirmed and widely adopted in this and other types of wounds, it could be a useful tool in both the clinical and research setting.
Rho Kinase (ROCK) Inhibitors and Their Therapeutic Potential (2015)

Rho kinases (ROCKs) belong to the serine-threonine family, the inhibition of which affects the function of many downstream substrates. As such, ROCK inhibitors have potential therapeutic applicability in a wide variety of pathological conditions including asthma, cancer, erectile dysfunction, glaucoma, insulin resistance, kidney failure, neuronal degeneration, and osteoporosis. To date, two ROCK inhibitors have been approved for clinical use in Japan (fasudil and ripasudil) and one in China (fasudil). In 1995 fasudil was approved for the treatment of cerebral vasospasm, and more recently, ripasudil was approved for the treatment of glaucoma in 2014. In this Perspective, we present a comprehensive review of the physiological and biological functions for ROCK, the properties and development of over 170 ROCK inhibitors as well as their therapeutic potential, the current status, and future considerations.
COX-2 inhibition is neither necessary nor sufficient for celecoxib to suppress tumor cell proliferation and focus formation in vitro (2008)

The antitumor activity of celecoxib in vitro did not involve the inhibition of COX-2. Rather, the drug's ability to trigger ERS, a known effector of cell death, might provide an alternative explanation for its acute cytotoxicity. In addition, the newly discovered ability of this drug to restore contact inhibition and block focus formation during chronic drug exposure, which involved neither ERS nor COX-2, suggests a novel, as yet unrecognized mechanism of celecoxib action.
Paramagnetic Polymerized Liposomes: Synthesis, Characterization, and Applications for Magnetic Resonance Imaging (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTParamagnetic Polymerized Liposomes: Synthesis, Characterization, and Applications for Magnetic Resonance ImagingRichard W. Storrs, Francois D. Tropper, Henry Y. Li, Curtis K. Song, Jeremy K. Kuniyoshi, Dorothy A. Sipkins, King C. P. Li, and Mark D. BednarskiCite this: J. Am. Chem. Soc. 1995, 117, 28, 7301–7306Publication Date (Print):July 1, 1995Publication History Published online1 May 2002Published inissue 1 July 1995https://pubs.acs.org/doi/10.1021/ja00133a001https://doi.org/10.1021/ja00133a001research-articleACS PublicationsRequest reuse permissionsArticle Views810Altmetric-Citations88LEARN 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
Camera calibration: a quick and easy way to determine the scale factor (1991)

The author presents a quick and easy solution to the camera calibration problem of finding the scale factor that arises because of a difference between the scanning frequency of the camera sensor plane and the scanning frequency of the image capture board frame buffer. The method presented is based on the observation that the scale factor is related to the distortion in an image of a circle: this is a distortion that can easily be measured by considering the occluding boundary of a precisely fabricated sphere, such as a ball bearing. Implementation results are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Algorithmic Composition (2013)

Composers have used formalized procedures to create music throughout history. With the advent of the computer, algorithmic composition allows composers not only to create and experiment with different formalisms, but to hear and evaluate results quickly. Often in algorithmic composition, the composer has only a vague idea how the output will sound, but because the input is highly automated, the composer can make adjustments to take advantage of happy accidents, program bugs, and other creative sources of sound. Algorithmic Composition: A Guide to Composing Music with Nyquist provides an overview of procedural approaches to music generation. It introduces programming concepts through many examples written using the Nyquist system for music composition and sound synthesis. Nyquist is freely available software, and over 100 program examples from this book are available in electronic form. Readers will be well equipped to develop their own algorithms for composition. Music students who are learning about computer music and electronic music will all be interested in this innovative book, as generative music becomes an important part of the future of the discipline. Students and scholars in computer science will also find much to interest them, in a straightforward and fun way.
Substrate Preferences of a Lysophosphatidylcholine Acyltransferase Highlight Its Role in Phospholipid Remodeling (2008)

An important enzyme involved in phospholipid turnover is the acyl-CoA: lysophosphatidylcholine acyltransferase (LPCAT). Here, we report characterization of a newly discovered human LPCAT (LPCAT3), which has distinct substrate preferences strikingly consistent with a role in phosphatidylcholine (PtdCho) remodeling and modulating fatty acid composition of PtdCho. LPCAT3 prefers lysophosphatidylcholine (lysoPtdCho) with saturated fatty acid at the sn-1 position and exhibits acyl donor preference towards linoleoyl-CoA and arachidonoyl-CoA. Furthermore, LPCAT3 is active in mediating 1-O-alkyl-sn-glycero-3-phosphocholine acylation with long chain fatty acyl-CoAs to generate 1-O-alkyl-phosphatidylcholine, another very important constitute of mammalian membrane systems. These properties are precisely the known attributes of LPCAT previously ascribed to the isoform involved in Lands' cycle, and thus strongly suggest that LPCAT3 is involved in phospholipids remodeling to achieve appropriate membrane lipid fatty acid composition.
Branhamella cattarhalis: Antigenic Determinants and the Development of the IgG Subclass Response in Childhood (1990)

A recently developed whole cell ELISA was used to investigate the development of IgG subclass antibodies to Branhamella catarrhalis in childhood. In addition, SDS-PAGE and immunoblotting were used to study the interaction between the outer membrane proteins (OMPs) of B. catarrhalis and IgG subclass antibodies. Specific IgG3 antibodies were undetectable or present only in low amounts in children less than 4 years old but were an important constituent of the response of older children. OMPs prepared from different isolates had similar molecular masses and bound IgG with identical immunoblotting patterns. Binding appeared subclass-specific, with IgG3 binding to the broadest range of OMPs. These findings should provide a better understanding of the pathogenic role of this organism and suggest possible strategies for the development of a vaccine.