gebhart/patrepeval huggingface dataset:
Unitary hypothesis for multiple triggers of the pain and strain of migraine (2005)

Migraine headache is triggered by and associated with a variety of hormonal, emotional, nutritional, and physiological changes. The perception of migraine headache is formed when nociceptive signals originating in the meninges are conveyed to the somatosensory cortex through the trigeminal ganglion, medullary dorsal horn, and thalamus. Is there a common descending pathway accounting for the activation of meningeal nociceptors by different migraine triggers? We propose that different migraine triggers activate a wide variety of brain areas that impinge on parasympathetic neurons innervating the meninges. According to this hypothesis, migraine triggers such as perfume, stress, or awakening activate multiple hypothalamic, limbic, and cortical areas, all of which contain neurons that project to the preganglionic parasympathetic neurons in the superior salivatory nucleus (SSN). The SSN, in turn, activates postganglionic parasympathetic neurons in the sphenopalatine ganglion, resulting in vasodilation and local release of inflammatory molecules that activate meningeal nociceptors. Are there ascending pathways through which the trigeminovascular system can induce the wide variety of migraine symptoms? We propose that trigeminovascular projections from the medullary dorsal horn to selective areas in the midbrain, hypothalamus, amygdala, and basal forebrain are functionally positioned to produce migraine symptoms such as irritability, loss of appetite, fatigue, depression, or the quest for solitude. Bidirectional trafficking by which the trigeminovascular system can activate the same brain areas that have triggered its own activity in the first place provides an attractive network of perpetual feedback that drives a migraine attack for many hours and even days.
I-131 tositumomab (2010)

I-131 tositumomab is a safe and effective option for patients with recurrent, refractory, or transformed FL and carries promise in the upfront treatment of FL, aggressive B-NHL, and as a transplant conditioning regimen.
The shape of a marine streamer in a cross current (1989)

Abstract A serious problem in marine data collection (particularly 3-D) is the necessity to assign to each hydrophone a precise location on the surface of the earth. The data available for this purpose can come from the vessel's navigation system, a radio beacon (at the tail buoy), an acoustic transponder (at the head of the streamer and occasionally elsewhere), and magnetic compasses distributed over the length of the cable. The shape of the streamer is commonly reconstructed by fitting a curve's tangents to the compass readings. The shape deduced in this fashion is highly sensitive to compass errors.As an alternative to the ad hoc numerical fit, we have derived the shape of the streamer in a cross current from physical principles. The mechanical equilibrium of tension and drag forces leads to differential equations which we integrate analytically to obtain a formal solution for the tension. A further analytic integration yields an equation (containing two integration constants) that relates arc length along the cable to the tangent angle. This equation can be matched to compass readings (for stability and minimum error) by a least-squares estimation of the integration constants. A satisfactory fit is obtained with a representative data set. Parametric equations are also obtained for x and y along the cable (with the x-axis in the fluid flow direction), as functions of the tangent angle; they contain the same integration constants (evaluated by the previous procedure). Elimination of the angle between the two parametric equations yields the equation of the cable shape in Cartesian coordinates.
Mechanical discoordination rather than dyssynchrony predicts reverse remodeling upon cardiac resynchronization (2008)

By current guidelines a considerable part of the patients selected for cardiac resynchronization therapy (CRT) do not respond to the therapy. We hypothesized that mechanical discoordination [opposite strain within the left ventricular (LV) wall] predicts reversal of LV remodeling upon CRT better than mechanical dyssynchrony. MRI tagging images were acquired in CRT candidates (n = 19) and in healthy control subjects (n = 9). Circumferential strain (epsilon(cc)) was determined in 160 regions. From epsilon(cc) signals we derived 1) an index of mechanical discoordination [internal stretch fraction (ISF), defined as the ratio of stretch to shortening during ejection] and 2) indexes of mechanical dyssynchrony: the 10-90% width of time to onset of shortening, time to peak shortening, and end-systolic strain. LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), and ejection fraction (LVEF) were determined before and after 3 mo of CRT. Responders were defined as those patients in whom LVESV decreased by >15%. In responders (n = 10), CRT increased LVEF and decreased LVEDV and LVESV (11 +/- 6%, 21 +/- 16%, and 30 +/- 16%, respectively) significantly more (P < 0.05) than in nonresponders (1 +/- 6%, 3 +/- 4%, and 5 +/- 10%, respectively). Among mechanical indexes, only ISF was different between responders and nonresponders (0.53 +/- 0.25 vs. 0.31 +/- 0.16; P < 0.05). In patients with ISF >0.4 (n = 10), LVESV decreased by 31 +/- 18% vs. 5 +/- 11% in patients with ISF <0.4 (P < 0.05). We conclude that mechanical discoordination, as estimated from ISF, is a better predictor of reverse remodeling after CRT than differences in time to onset and time to peak shortening. Therefore, discoordination rather than dyssynchrony appears to reflect the reserve contractile capacity that can be recruited by CRT.
Comprehensive Binary Interaction Mapping of SH2 Domains via Fluorescence Polarization Reveals Novel Functional Diversification of ErbB Receptors (2012)

First-generation interaction maps of Src homology 2 (SH2) domains with receptor tyrosine kinase (RTK) phosphosites have previously been generated using protein microarray (PM) technologies. Here, we developed a large-scale fluorescence polarization (FP) methodology that was able to characterize interactions between SH2 domains and ErbB receptor phosphosites with higher fidelity and sensitivity than was previously achieved with PMs. We used the FP assay to query the interaction of synthetic phosphopeptides corresponding to 89 ErbB receptor intracellular tyrosine sites against 93 human SH2 domains and 2 phosphotyrosine binding (PTB) domains. From 358,944 polarization measurements, the affinities for 1,405 unique biological interactions were determined, 83% of which are novel. In contrast to data from previous reports, our analyses suggested that ErbB2 was not more promiscuous than the other ErbB receptors. Our results showed that each receptor displays unique preferences in the affinity and location of recruited SH2 domains that may contribute to differences in downstream signaling potential. ErbB1 was enriched versus the other receptors for recruitment of domains from RAS GEFs whereas ErbB2 was enriched for recruitment of domains from tyrosine and phosphatidyl inositol phosphatases. ErbB3, the kinase inactive ErbB receptor family member, was predictably enriched for recruitment of domains from phosphatidyl inositol kinases and surprisingly, was enriched for recruitment of domains from tyrosine kinases, cytoskeletal regulatory proteins, and RHO GEFs but depleted for recruitment of domains from phosphatidyl inositol phosphatases. Many novel interactions were also observed with phosphopeptides corresponding to ErbB receptor tyrosines not previously reported to be phosphorylated by mass spectrometry, suggesting the existence of many biologically relevant RTK sites that may be phosphorylated but below the detection threshold of standard mass spectrometry procedures. This dataset represents a rich source of testable hypotheses regarding the biological mechanisms of ErbB receptors.
Analysis of the Mechanism of Action of Anti‐human Interleukin‐6 and Anti‐human Interleukin‐6 Receptor‐neutralising Monoclonal Antibodies (1997)

Anti-human interleukin-6 (human IL-6) and anti-human IL-6 receptor (IL-6R)-neutralising monoclonal antibodies (mAbs) are among the most promising human IL-6-specific inhibitors and have been shown to exert short-term beneficial effects in clinical trials. Simultaneous treatment with different anti-human IL-6 or anti-human IL-6R mAbs was recently suggested to be a potent way to inhibit the action of the cytokine in vivo. Although some of these mAbs are already used, their mechanisms of action and the location of their epitopes on the surface of human IL-6 and human IL-6R are still unknown. Here, we analysed the capacity of several anti-human IL-6 and anti-human IL-6R mAbs to inhibit the interaction between human IL-6, human IL-6R, and human glycoprotein 130 (gp130). We mapped the epitopes of several of these mAbs by studying their binding to human IL-6 and human IL-6R mutant proteins. Our results show that several anti-human IL-6 and anti-human IL-6R-neutralising mAbs block the binding between human IL-6 and human IL-6R, whereas others block the binding to gp130. We provide evidence that some of the latter mAbs inhibit interaction with gp130beta1, whereas others interfere with the binding to gp130beta2. Our results suggest that residues included in the C'D' loop of human IL-6R interact with gp130beta2.
TIAM1 Antagonizes TAZ/YAP Both in the Destruction Complex in the Cytoplasm and in the Nucleus to Inhibit Invasion of Intestinal Epithelial Cells (2017)

Aberrant WNT signaling drives colorectal cancer (CRC). Here, we identify TIAM1 as a critical antagonist of CRC progression through inhibiting TAZ and YAP, effectors of WNT signaling. We demonstrate that TIAM1 shuttles between the cytoplasm and nucleus antagonizing TAZ/YAP by distinct mechanisms in the two compartments. In the cytoplasm, TIAM1 localizes to the destruction complex and promotes TAZ degradation by enhancing its interaction with βTrCP. Nuclear TIAM1 suppresses TAZ/YAP interaction with TEADs, inhibiting expression of TAZ/YAP target genes implicated in epithelial-mesenchymal transition, cell migration, and invasion, and consequently suppresses CRC cell migration and invasion. Importantly, high nuclear TIAM1 in clinical specimens associates with increased CRC patient survival. Together, our findings suggest that in CRC TIAM1 suppresses tumor progression by regulating YAP/TAZ activity.
Near-Infrared Optical Imaging of Protease Activity for Tumor Detection (1999)

Tumor proteases can be used as molecular targets, allowing visualization of millimeter-sized tumors. The development of this technology, probe design, and optical imaging systems hold promise for molecular imaging, cancer detection, and evaluation of treatment.
Determination of molecular asymmetry in the phosphatidylethanolamine surface distribution in mixed phospholipid vesicles (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDetermination of molecular asymmetry in the phosphatidylethanolamine surface distribution in mixed phospholipid vesiclesBurton J. LitmanCite this: Biochemistry 1974, 13, 14, 2844–2848Publication Date (Print):July 1, 1974Publication History Published online1 May 2002Published inissue 1 July 1974https://pubs.acs.org/doi/10.1021/bi00711a010https://doi.org/10.1021/bi00711a010research-articleACS PublicationsRequest reuse permissionsArticle Views136Altmetric-Citations76LEARN 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
SIL: Modeling and Measuring Scalable Peer-to-Peer Search Networks (Extended version) (2002)

Abstract. The popularity of peer-to-peer search networks continues to grow, even as the limitations to the scalability of existing systems become apparent. We pro-pose a simple model for search networks, called the Search/Index Links (SIL) model. The SIL model describes existing networks while also yielding organiza-tions not previously studied. Using analytical and simulation results, we argue that one new organization, parallel search clusters, is superior to existing supernode networks in many cases. 1
Economic impact of biofouling on a naval surface ship (2010)

In the present study, the overall economic impact of hull fouling on a mid-sized naval surface ship (Arleigh Burke-class destroyer DDG-51) has been analyzed. A range of costs associated with hull fouling was examined, including expenditures for fuel, hull coatings, hull coating application and removal, and hull cleaning. The results indicate that the primary cost associated with fouling is due to increased fuel consumption attributable to increased frictional drag. The costs related to hull cleaning and painting are much lower than the fuel costs. The overall cost associated with hull fouling for the Navy's present coating, cleaning, and fouling level is estimated to be $56M per year for the entire DDG-51 class or $1B over 15 years. The results of this study provide guidance as to the amount of money that can be reasonably spent for research, development, acquisition, and implementation of new technologies or management strategies to combat hull fouling.
ZIF-8@PBI-BuI composite membranes: elegant effects of PBI structural variations on gas permeation performance (2014)

The composites of metal organic frameworks (MOFs) and polymers look promising as membrane materials for gas separation, provided benefits of both the components can be shown successfully. This work shows that the structural architecture of polybenzimidazole (PBI) is highly advantageous in offering attractive gas permeation properties of its composites with MOFs. PBI-BuI and its N-substituted (methyl and 4-tert-butylbenzyl) derivatives were blended with ZIF-8. In general, homogeneous blend formation of ZIF-8 was achieved with all three polymers, as supported by SEM. Wide angle X-ray diffraction, mechanical property analysis and density measurements of the composite membranes were performed in order to understand the effects of physical blending of MOFs and polymers. Gas permeability analysis of the composite membranes revealed that the properties of MOFs as well as those of polymers arising from their structural architecture are responsible for governing the permeability and selectivity of the resulting composites.
Demonstration of Dispersion-Canceled Quantum-Optical Coherence Tomography (2003)

We present an experimental demonstration of quantum-optical coherence tomography. The technique makes use of an entangled twin-photon light source to carry out axial optical sectioning. It is compared to conventional optical coherence tomography. The immunity of the quantum version to dispersion, as well as a factor of 2 enhancement in resolution, is experimentally demonstrated.
Accumulation of p53 Tumor Suppressor Gene Protein: An Independent Marker of Prognosis in Breast Cancers (1992)

Immunohistochemically detected p53 protein accumulation was an independent marker of shortened survival and was seen more often in familial than in sporadic carcinomas. Our findings also suggest a correlation between p53 protein accumulation and p53 gene mutation.
The colony-stimulating factors and collagen-induced arthritis: exacerbation of disease by M-CSF and G-CSF and requirement for endogenous M-CSF (2000)

There is increasing evidence that the colony-stimulating factors (CSFs) may play a part in chronic inflammatory autoimmune diseases, such as rheumatoid arthritis (RA). We examined the involvement of macrophage CSF (M-CSF or CSF-1) and granulocyte CSF (G-CSF) in collagen-induced arthritis (CIA), a murine model of RA. Daily injections of M-CSF or G-CSF, 20-24 days postprimary immunization with type II collagen, exacerbated disease symptoms in suboptimally immunized DBA/1 mice. Support for the involvement of endogenous M-CSF in CIA was obtained by studies in which neutralizing monoclonal antibody reduced the severity of established CIA and also by studies showing the resistance of M-CSF-deficient op/op mice to CIA induction. These studies show that M-CSF and G-CSF can be proinflammatory in CIA and provide evidence that macrophage- and granulocyte-lineage cells can exacerbate CIA. Our results also show that M-CSF-dependent cells are essential for CIA development, suggesting M-CSF may be a suitable target for therapeutic intervention in RA.
Siglec-8 (2000)

We describe the characterization of siglec-8, a novel sialic acid-binding immunoglobulin-like lectin that is expressed specifically by eosinophils. A full-length cDNA encoding siglec-8 was isolated from a human eosinophil cDNA library. Siglec-8 is predicted to contain three extracellular immunoglobulin-like domains, a transmembrane region, and a cytoplasmic tail of 47 amino acids. The siglec-8 gene mapped on chromosome 19q13.33-41, closely linked to genes encoding CD33 (siglec-3), siglec-5, siglec-6, and siglec-7. When siglec-8 was expressed on COS cells or as a recombinant protein fused to the Fc region of human IgG(1), it was able to mediate sialic acid-dependent binding to human erythrocytes and to soluble sialoglycoconjugates. Using specific monoclonal antibodies, siglec-8 could be detected only on eosinophils and hence appears to be the first example of an eosinophil-specific transmembrane receptor.
Myenteric Plexus of the Hind‐Gut: Developmental Abnormalities in Humans and Experimental Studies (1981)

Intraluminal pressure studies on patients with congenital aganglionosis showed that the aganglionic rectum contracted in an uncoordinated manner and failed to relax. Histochemical assessment of the innervation helped to explain the variable severity of the symptoms in this condition. It is concluded that (1) absence of ganglia prevents normal coordinated peristalsis and creates an obstructive element; (2) absence of reflex relaxation adds to the obstruction; (3) the degree of uncoordinated motor activity in distal aganglionic bowel probably relates to the number of cholinesterase-positive nerves in the circular muscle and adds another variable obstructive element; and (4) deficient innervation of distal ganglionic bowel probably creates a poor propulsive force and so accentuates more distal obstructive factors. Neurohistochemical and functional studies in the anorectum of cats reveal a somewhat different innervation pattern from that in humans but show that sphincteric tone is mainly due to alpha-adrenergic neural activity. Reflex relaxation of the internal anal sphincter is a complex function in which inhibitory responses override motor responses, and it involves an important non-adrenergic non-cholinergic component. The role of cholinergic nerves in the sphincter remains uncertain. Neurohistochemical assessment of full thickness biopsy specimens of rectal muscle from patients with disabling constipation shows that developmental neuronal dysplasias of the hind-gut may be divided into three main categories: (1) aganglionosis (Hirschsprung's disease), (2) hypoganglionosis and (3) hyperganglionosis, and that the different neuronal elements may be affected to differing degrees in individuals within each group. Resection of the aganglionic bowel is required in congenital aganglionosis but the combined diagnostic-therapeutic procedure of anorectal myotomy has been found beneficial in patients with hypoganglionosis.
Inactivation of E. Coli and S. Cerevisiae by Pulsed Electric Fields Under Controlled Temperature Conditions (1994)

To study the feasibility of high-voltage pulsed electric field treatment as a food pasteurization technique, a static treatment unit was constructed to process 25 mL batches of foods with electric field strengths up to 40 kV/cm. A heat transfer model was developed to predict fluid food temperatures during the application of pulsed electric fields in the microbial inactivation tests. The heat transfer model was verified by comparing model predictions with experimental measurements. While maintaining fluid food temperatures below 25 C, E. coli and S. cerevisiae suspensions were treated with pulsed electric fields. A three to four decimal reduction in microbial viability was observed.
Covalent agonists for studying G protein-coupled receptor activation (2014)

Structural studies on G protein-coupled receptors (GPCRs) provide important insights into the architecture and function of these important drug targets. However, the crystallization of GPCRs in active states is particularly challenging, requiring the formation of stable and conformationally homogeneous ligand-receptor complexes. Native hormones, neurotransmitters, and synthetic agonists that bind with low affinity are ineffective at stabilizing an active state for crystallogenesis. To promote structural studies on the pharmacologically highly relevant class of aminergic GPCRs, we here present the development of covalently binding molecular tools activating Gs-, Gi-, and Gq-coupled receptors. The covalent agonists are derived from the monoamine neurotransmitters noradrenaline, dopamine, serotonin, and histamine, and they were accessed using a general and versatile synthetic strategy. We demonstrate that the tool compounds presented herein display an efficient covalent binding mode and that the respective covalent ligand-receptor complexes activate G proteins comparable to the natural neurotransmitters. A crystal structure of the β2-adrenoreceptor in complex with a covalent noradrenaline analog and a conformationally selective antibody (nanobody) verified that these agonists can be used to facilitate crystallogenesis.
Overexpression of A1, an NF-κB–Inducible Anti-Apoptotic Bcl Gene, Inhibits Endothelial Cell Activation (1999)

A1 is an anti-apoptotic bcl gene that is expressed in endothelial cells (EC) in response to pro-inflammatory stimuli. We show that in addition to protecting EC from apoptosis, A1 inhibits EC activation and its associated expression of pro-inflammatory proteins by inhibiting the transcription factor nuclear factor (NF)-κB. This new anti-inflammatory function gives a broader dimension to the protective role of A1 in EC. We also show that activation of NF-κB is essential for the expression of A1. Taken together, our data suggest that A1 downregulates not only the pro-apoptotic and pro-inflammatory response, but also its own expression, thus restoring a quiescent phenotype to EC.
Generation of cloned adult muscular pigs with myostatin gene mutation by genetic engineering (2017)

Skeletal muscle is the most economically valuable tissue in meat-producing animals and enhancing muscle growth in these species may enhance the efficiency of meat production.