gebhart/patrepeval huggingface dataset:
Protease‐activated receptor 2 sensitizes TRPV1 by protein kinase Cɛ‐ and A‐dependent mechanisms in rats and mice (2006)

Proteases that are released during inflammation and injury cleave protease-activated receptor 2 (PAR2) on primary afferent neurons to cause neurogenic inflammation and hyperalgesia. PAR2-induced thermal hyperalgesia depends on sensitization of transient receptor potential vanilloid receptor 1 (TRPV1), which is gated by capsaicin, protons and noxious heat. However, the signalling mechanisms by which PAR2 sensitizes TRPV1 are not fully characterized. Using immunofluorescence and confocal microscopy, we observed that PAR2 was colocalized with protein kinase (PK) Cepsilon and PKA in a subset of dorsal root ganglia neurons in rats, and that PAR2 agonists promoted translocation of PKCepsilon and PKA catalytic subunits from the cytosol to the plasma membrane of cultured neurons and HEK 293 cells. Subcellular fractionation and Western blotting confirmed this redistribution of kinases, which is indicative of activation. Although PAR2 couples to phospholipase Cbeta, leading to stimulation of PKC, we also observed that PAR2 agonists increased cAMP generation in neurons and HEK 293 cells, which would activate PKA. PAR2 agonists enhanced capsaicin-stimulated increases in [Ca2+]i and whole-cell currents in HEK 293 cells, indicating TRPV1 sensitization. The combined intraplantar injection of non-algesic doses of PAR2 agonist and capsaicin decreased the latency of paw withdrawal to radiant heat in mice, indicative of thermal hyperalgesia. Antagonists of PKCepsilon and PKA prevented sensitization of TRPV1 Ca2+ signals and currents in HEK 293 cells, and suppressed thermal hyperalgesia in mice. Thus, PAR2 activates PKCepsilon and PKA in sensory neurons, and thereby sensitizes TRPV1 to cause thermal hyperalgesia. These mechanisms may underlie inflammatory pain, where multiple proteases are generated and released.
An open label study of the effects of rituximab in neuromyelitis optica (2005)

Eight patients with worsening neuromyelitis optica were treated with rituximab to achieve B cell depletion. Treatment was well tolerated. Six of eight patients were relapse free and median attack rate declined from 2.6 attacks/patient/year to 0 attacks/patient/year (p = 0.0078). Seven of eight patients experienced substantial recovery of neurologic function over 1 year of average follow-up. The pretreatment median Expanded Disability Status Scale score was 7.5, and at follow-up examination was 5.5 (p = 0.013).
Rocket observation of atomic oxygen and night airglow: Measurement of concentration with an improved resonance fluorescence technique (1996)

<strong class="journal-contentHeaderColor">Abstract.</strong> An improved resonant fluorescence instrument for measuring atomic oxygen concentration was developed to avoid the Doppler effect and the aerodynamic shock effect due to the supersonic motion of a rocket. The shock effect is reduced by adopting a sharp wedge-shaped housing and by scanning of the detector field of view to change the distance between the scattering volume and the surface of the housing. The scanning enables us to determine absolute values of atomic oxygen concentration from relative variation of the scattered light signal due to the self-absorption. The instrument was calibrated in the laboratory, and the numerical simulation reproduced the calibration result. Using the instrument, the altitude profile of atomic oxygen concentration was observed by a rocket experiment at Uchinoura (31Â°N) on 28 January 1992. The data obtained from the rocket experiment were not perfectly free from the shock effect, but errors due to the effect were reduced by the data analysis procedure. The observed maximum concentration was 3.8Ã 10<sup>11</sup> cm<sup>â3</sup> at altitudes around 94 km. The systematic error is estimated to be less than Â±0.7Ã10<sup>11</sup> cm<sup>â3</sup> and the relative random error is less thanÂ±0.07Ã 10<sup>11</sup> cm<sup>â3</sup>at the same altitudes. The altitude profile of the OI 557.7-nm airglow was also observed in the same rocket experiment. The maximum volume emission rate was found to be 150 photons cm<sup>â3</sup> s<sup>â1</sup> at 94 km. The observed altitude profiles are compared with the MSIS model and other in situ observations.
Continuous time realization of time-stretch ADC (2006)

We present computational and experimental results for the time-stretch photonic ADC that show this technology can be used to compress bandwidth and digitize continuous-time RF signals. The key to continuous time operation is our demonstration that novel low-loss dispersive elements, such as chirp fiber Bragg gratings, can replace lossy dispersion compensation fiber in the time stretch ADC. Carrier-to-noise ratio calculations are presented showing the impact of CFBGs on design of a high-resolution continuous-time ADC
Mechanism of intestinal absorption and brain uptake of L-5-hydroxytryptophan in rats, as compared to those of L-3,4-dihydroxyphenylalanine. (1977)

L-5-Hydroxytryptophan (5-HTP) and L-3, 4-dihydroxyphenylalanine (DOPA) were comparatively investigated of their mechanisms of intestinal absorption, metabolism in the intestine and liver tissues and mechanisms of passage through the blood-brain barriers, by means of in vitro and/or in situ techniques using rat tissues. The corresponding D-isomers were also investigated for comparison. L-5-HTP, but not the D-isomer, was found to be absorbed from the intestine by an active transport mechanism in the same way as L-DOPA. In vitro studies using rat brain cortex slices proved that both L-5-HTP and L-DOPA, but not their D-isomers, are taken up by the brain tissues by an active transport mechanism which is saturable, energy-dependent and competitive. There was no substantial difference between L-5-HTP and L-DOPA in the rate of intestinal absorption and that of brain uptake. It was indicated, however, that L-5-HTP was decarboxylated in the intestine to a much less extent than L-DOPA during the absorption and the decarboxylation activity of rat intestine and liver homogenates was found to be about four and seven times higher for L-DOPA than for L-5-HTP, respectively. The latter results suggest that the oral dose of L-5-HTP can be much more easily transferred into the circulating blood without being suffered from decarboxylation in the peripheral organs than L-DOPA, resulting in a more efficient penetration of L-5-HTP into the brain as a serotonine precursor.
Environmental chamber for in situ dynamic control of temperature and relative humidity during x-ray scattering (2012)

We have designed, constructed, and evaluated an environmental chamber that has in situ dynamic control of temperature (25 to 90 °C) and relative humidity (0% to 95%). The compact specimen chamber is designed for x-ray scattering in transmission with an escape angle of 2θ = ±30°. The specimen chamber is compatible with a completely evacuated system such as the Rigaku PSAXS system, in which the specimen chamber is placed inside a larger evacuated chamber (flight path). It is also compatible with x-ray systems consisting of evacuated flight tubes separated by small air gaps for sample placement. When attached to a linear motor (vertical displacement), the environmental chamber can access multiple sample positions. The temperature and relative humidity inside the specimen chamber are controlled by passing a mixture of dry and saturated gas through the chamber and by heating the chamber walls. Alternatively, the chamber can be used to control the gaseous environment without humidity. To illustrate the value of this apparatus, we have probed morphology transformations in Nafion(®) membranes and a polymerized ionic liquid as a function of relative humidity in nitrogen.
Template-assisted electrodeposition of SixGe1−x nanowires with varying length and composition from two different ionic liquids (2009)

We have recently reported that “luminescent” SixGe1−x can be electrodeposited from 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)amide ([Py1,4]Tf2N) at room temperature. Interestingly, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide ([EMIm]Tf2N) ionic liquid delivers a germanium-rich SixGe1−x showing also a quantum-size effect, as revealed in the present study. These results led us to evaluate the possibility of obtaining high quality SixGe1−xnanowires from two different ionic liquids by the simple and inexpensive template-assisted electrochemical pathway. Herein, we report for the first time on the room temperature template synthesis of SixGe1−xnanowires by potentiostatic electrochemical deposition from the air- and water-stable ionic liquids [Py1,4]Tf2N and [EMIm]Tf2N containing (each) GeCl4 and SiCl4 as precursors. As a first step, a commercially available track-etched polycarbonate membrane (PC) with an average nominal pore diameter of 90 nm was used as template. SixGe1−xnanowires with an average diameter corresponding to the nanopores' diameter and lengths of 1 to 2.5 µm were reproducibly obtained. [EMIm]Tf2N delivers longer SixGe1−xnanowires than [Py1,4]Tf2N under the same parameters and reaction conditions. Characterization of the nanowires was performed by EDX and HR-SEM.
Translational control of malignancy: the mRNA cap-binding protein, eIF-4E, as a central regulator of tumor formation, growth, invasion and metastasis. (2000)

Recent studies have implicated the mRNA cap-binding protein, eIF-4E, as a key regulator of malignant progression. Indeed, the major intracellular signaling pathways involved in tumor growth and malignancy, the MAP kinase and PI3 kinase pathways, induce eIF-4E activity. Furthermore, immunohistochemical analyses have revealed that eIF-4E is overexpressed and related to disease progression in human cancers of the colon, head and neck, and breast. In experimental tumors, manipulation of eIF-4E function profoundly affects not only tumorigenesis but also tumor invasion and metastasis. While increasing global protein synthesis rates, the increased activity of eIF-4E that typifies both human and experimental tumors disproportionately enhances the translation of a specific array of potent growth regulatory and malignancy-related proteins, including c-myc, cyclin D1, ornithine decarboxylase, vascular endothelial growth factor, basic fibroblast growth factor and others. Herein, we review the data supporting the notion that, by coordinately upregulating the translation of numerous malignancy-related proteins, eIF-4E plays a pivotal role in regulating not only tumor growth, but also invasion and metastasis.
Distinctive patterns of DNA methylation associated with Parkinson disease (2013)

Parkinson disease (PD) is a multifactorial neurodegenerative disorder with high incidence in the elderly, where environmental and genetic factors are involved in etiology. In addition, epigenetic mechanisms, including deregulation of DNA methylation have been recently associated to PD. As accurate diagnosis cannot be achieved pre-mortem, identification of early pathological changes is crucial to enable therapeutic interventions before major neuropathological damage occurs. Here we investigated genome-wide DNA methylation in brain and blood samples from PD patients and observed a distinctive pattern of methylation involving many genes previously associated to PD, therefore supporting the role of epigenetic alterations as a molecular mechanism in neurodegeneration. Importantly, we identified concordant methylation alterations in brain and blood, suggesting that blood might hold promise as a surrogate for brain tissue to detect DNA methylation in PD and as a source for biomarker discovery.
Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia A (2013)

Neutralizing antibodies (inhibitors) toward factor VIII form a severe complication in nonsevere hemophilia A, profoundly aggravating the bleeding pattern. Identification of high-risk patients is hampered by lack of data that take exposure days to therapeutic factor VIII concentrates into account. In the INSIGHT study, we analyzed the association between F8 mutation and inhibitor development in patients with nonsevere hemophilia A (factor VIII 2-40 IU/dL). This analysis included 1112 nonsevere hemophilia A patients from 14 centers in Europe and Australia that had genotyped at least 70% of their patients. Inhibitor risk was calculated as Kaplan-Meier incidence with cumulative number of exposure days as the time variable. During 44 800 exposure days (median, 24 exposure days per patient; interquartile range [IQR], 7-90), 59 of the 1112 patients developed an inhibitor; cumulative incidence of 5.3% (95% confidence interval [CI], 4.0-6.6) after a median of 28 exposure days (IQR, 12-71). The inhibitor risk at 50 exposure days was 6.7% (95% CI, 4.5-8.9) and at 100 exposure days the risk further increased to 13.3% (95% CI, 9.6-17.0). Among a total of 214 different F8 missense mutations 19 were associated with inhibitor development. These results emphasize the importance of F8 genotyping in nonsevere hemophilia A.
Inhibitory effect of amygdalin on lipopolysaccharide-inducible TNF-alpha and IL-1beta mRNA expression and carrageenan-induced rat arthritis. (2008)

Amygdalin is a cyanogenic glycoside plant compound found in the seeds of rosaceous stone fruits. We evaluated the antiinflammatory and analgesic activities of amygdalin, using an in vitro lipopolysaccharide (LPS)-induced cell line and a rat model with carrageenan-induced ankle arthritis. One mM amygdalin significantly inhibited the expression of TNF-alpha and IL-1beta mRNAs in LPS-treated RAW 264.7 cells. Amygdalin (0.005, 0.05, and 0.1 mg/kg) was intramuscularly injected immediately after the induction of carrageenan-induced arthritic pain in rats, and the anti-arthritic effect of amygdalin was assessed by measuring the weight distribution ratio of the bearing forces of both feet and the ankle circumference, and by analyzing the expression levels of three molecular markers of pain and inflammation (c-Fos, TNF-alpha, and IL-1beta) in the spinal cord. The hyperalgesia of the arthritic ankle was alleviated most significantly by the injection of 0.005 mg/kg amygdalin. At this dosage, the expressions of c-Fos, TNF-alpha, and IL-1beta in the spinal cord were significantly inhibited. However, at dosage greater than 0.005 mg/kg, the painrelieving effect of amygdalin was not observed. Thus, amygdalin treatment effectively alleviated responses to LPStreatment in RAW 264.7 cells and carrageenan-induced arthritis in rats, and may serve as an analgesic for relieving inflammatory pain.
Fluorometric method for phenylalanine microplate assay adapted for phenylketonuria screening. (1989)

We adapted the method of McCaman and Robins for fluorometry of phenylalanine to a microplate assay for routine phenylketonuria screening. Sensitivity is 15 mumol/L for the plasma assay and 30 mumol/L for the dried blood-spot assay, with CV less than 10% for both assays. Results for human plasma by microplate assay correlated well (r = 0.99) with results of amino acid analyzer determination of phenylalanine. When measurements are performed in an automated reader, the microplate assay has considerable advantages over conventional measurements in cuvettes: smaller volumes of reagents and automation enabling high throughput and convenience. Because the described method is a quantitative one, we can postulate that, compared with the semiquantitative Guthrie inhibition bioassay, this microplate assay is more reliable, easier to perform, and about twofold less costly.
Histopathological studies on the local reactions induced by complete fReund's adjuvant (CFA), bacterial lipopolysaccharide (LPS), and synthetic lipopeptide (P3C) conjugates (1991)

The inflammatory reactions following subcutaneous application of adjuvants revealed characteristic pathological patterns. The injection of complete Freund's adjuvant (CFA) resulted in the formation of large lipid deposits encircled by an inflammatory reaction and concentrically arranged collagen bundles. Bacterial lipopolysaccharide (LPS) caused granulomatous aggregations of mononuclear cells with thrombotic vessel occlusions. Inoculation of the lipopeptide adjuvants induced accumulation of mononuclear cells with only minimal fibrotic changes which were resolved after day 28. Lipopeptide conjugates based on the head group tripalmitoyl-S-glyceryl-cysteinyl-serin (P3CS) can thus be used as effective immunogens and adjuvants without long-term tissue damage.
The Serotonin 1a Receptor Gene Contains a TATA-less Promoter that Responds to MAZ and Sp1 (1996)

The structure and function of the 5'-flanking region of the mouse and human serotonin 1a receptor gene have been analyzed by RNA 5' end mapping, DNA-protein interaction, and transient expression assays. A large number of mRNA 5' termini, detected by mapping 5' ends from mouse brain RNA, were found dispersed over a region of about 700 base pairs flanking the receptor coding sequence. Consistent with the apparently heterogeneous pattern of transcription initiation, the flanking DNA sequence lacked typical TATA box elements and was rich in guanine and cytosine. The mouse and human 5'-flanking sequences were 63% homologus and similarly organized. A guanine-cytosine-rich DNA sequence motif related to the sequence 5'-GGGG(C/A)GGGG-3' was repeated within the 5'-flanking region and located at or near several mRNA 5' ends. This DNA sequence motif bound to proteins in a crude HeLa cell nuclear extract. A cDNA encoding a protein that interacts with this sequence was cloned and found to be the MAZ (Pur-1, Zif87) protein. The interaction between MAZ and the receptor gene 5'-flanking region proximal to the protein coding sequence was examined by DNase I footprinting, and four sites of MAZ interaction were identified. Three of the four MAZ binding sites also were shown to interact with transcription factor Sp1. Overproduction of MAZ or Sp1 in transient transfection assays increased expression directed by the human 5'-flanking sequence, although MAZ was substantially more effective. This result suggests that MAZ and Sp1 both participate in regulating expression from the serotonin 1a receptor gene promoter, and it raises the possibility that MAZ may act at a variety of promoters through the guanosine-cytosine-rich sequences generally thought to serve as binding sites for the Sp1 family of transcription factors. Analysis of one of the guanosine-cytosine-rich DNA sequences also revealed that it can serve as a transcription initiator sequence in vitro. This initiator sequence differs from previously characterized initiators and may represent a new class of this transcriptional control sequence.
Protein Splicing and Auto-cleavage of Bacterial Intein-like Domains Lacking a C′-flanking Nucleophilic Residue (2004)

Bacterial intein-like (BIL) domains are newly identified homologs of intein protein-splicing domains. The two known types of BIL domains together with inteins and hedgehog (Hog) auto-processing domains form the Hog/intein (HINT) superfamily. BIL domains are distinct from inteins and Hogs in sequence, phylogenetic distribution, and host protein type, but little is known about their biochemical activity. Here we experimentally study the auto-processing activity of four BIL domains. An A-type BIL domain from Clostridium thermocellum showed both protein-splicing and auto-cleavage activities. The splicing is notable, because this domain has a native Ala C'-flanking residue rather than a nucleophilic residue, which is absolutely necessary for intein protein splicing. B-type BIL domains from Rhodobacter sphaeroides and Rhodobacter capsulatus cleaved their N' or C' ends. We propose an alternative protein-splicing mechanism for the A-type BIL domains. After an initial N-S acyl shift, creating a thioester bond at the N' end of the domain, the C' end of the domain is cleaved by Asn cyclization. The resulting amino end of the C'-flank attacks the thioester bond next at the N' end of the domain. This aminolysis step splices the two flanks of the domain. The B-type BIL domain cleavage activity is explained in the context of the canonical intein protein-splicing mechanism. Our results suggest that the different HINT domains have related biochemical activities of proteolytic cleavages, ligation and splicing. Yet the predominant reactions diverged in each HINT type according to their specific biological roles. We suggest that the BIL domain cleavage and splicing reactions are mechanisms for post-translationally generating protein variability, particularly in extracellular bacterial proteins.
Bayesian Model Combination (BAYCOM) for Improved Recognition (2006)

Combining the recognition outputs of multiple systems using methods such as ROVER or its extensions gives improved performance. However, previous approaches have been somewhat adhoc. We present BAYCOM, a Bayesian decision-theoretic approach to model combination that is optimal under given assumptions. We present recognition experiments showing that BAYCOM gives significant improvements over previous combination methods. In addition, we show that BAYCOM provides a confidence feature that gives very large improvements over previous methods for utterance rejection.
G Protein–Coupled Receptor Kinase 2 Ablation in Cardiac Myocytes Before or After Myocardial Infarction Prevents Heart Failure (2008)

Myocardial G protein-coupled receptor kinase (GRK)2 is a critical regulator of cardiac beta-adrenergic receptor (betaAR) signaling and cardiac function. Its upregulation in heart failure may further depress cardiac function and contribute to mortality in this syndrome. Preventing GRK2 translocation to activated betaAR with a GRK2-derived peptide that binds G(beta)gamma (betaARKct) has benefited some models of heart failure, but the precise mechanism is uncertain, because GRK2 is still present and betaARKct has other potential effects. We generated mice in which cardiac myocyte GRK2 expression was normal during embryonic development but was ablated after birth (alphaMHC-Cre x GRK2 fl/fl) or only after administration of tamoxifen (alphaMHC-MerCreMer x GRK2 fl/fl) and examined the consequences of GRK2 ablation before and after surgical coronary artery ligation on cardiac adaptation after myocardial infarction. Absence of GRK2 before coronary artery ligation prevented maladaptive postinfarction remodeling and preserved betaAR responsiveness. Strikingly, GRK2 ablation initiated 10 days after infarction increased survival, enhanced cardiac contractile performance, and halted ventricular remodeling. These results demonstrate a specific causal role for GRK2 in postinfarction cardiac remodeling and heart failure and support therapeutic approaches of targeting GRK2 or restoring betaAR signaling by other means to improve outcomes in heart failure.
Arbitrarily primed PCR fingerprinting of RNA (1992)

Fingerprinting of RNA populations was achieved using an arbitrarily selected primer at low stringency for first and second strand cDNA synthesis. PCR amplification was then used to amplify the products. The method required only a few nanograms of total RNA and was unaffected by low levels of genomic double stranded DNA contamination. A reproducible pattern of ten to twenty clearly visible PCR products was obtained from any one tissue. Differences in PCR fingerprints were detected for RNAs from the same tissue isolated from different mouse strains and for RNAs from different tissues from the same mouse. The strain-specific differences revealed are probably due to sequence polymorphisms and should be useful for genetic mapping of genes. The tissue-specific differences revealed may be useful for studying differential gene expression. Examples of tissue-specific differences were cloned. Differential expression was confirmed for these products by Northern analysis and DNA sequencing uncovered two new tissue-specific messages. The method should be applicable to the detection of differences between RNA populations in a wide variety of situations.