gebhart/patrepeval huggingface dataset:
Radiation-Induced Pulmonary Fibrosis: Examination of Chemokine and Chemokine Receptor Families (2002)

Fibrosis is a common outcome of chronic inflammation or injury. Pulmonary fibrosis may be the result of abnormal repair after an acute inflammatory response. The process of repair initiated by a tissue insult is largely a function of the activation of cells to produce important biological mediators such as cytokines, growth factors and chemokines, which orchestrate most aspects of the inflammatory response. Consequently, altered regulation of the production of inflammatory cell cytokines and chemokines after injury and repair likely contributes to the fibrosis. Our hypothesis is that chronic expression of specific chemokine and chemokine receptors during the fibrotic phase induced by thoracic irradiation may perpetuate the recruitment and activation of lymphocytes and macrophages, which may contribute to the development of fibrosis. Fibrosis-sensitive (C57BL/6) and fibrosis-resistant (C3H/HeJ) mice were irradiated with a single dose of 12.5 Gy to the thorax. Total lung RNA was prepared and hybridized using microarray analysis and RNase protection assays. At 26 weeks postirradiation, messages encoding the chemokines BLC (now known as Scyb13), C10 (now known as Scya6), IP-10 (now known as Scyb10), MCP-1 (now known as Scya2), MCP-3 (now known as Scya7), MIP-1gamma (now known as Scya9), and RANTES (now known as Scya5) and the chemokine receptors Ccr1, Ccr2, Ccr5 and Ccr6 were elevated in fibrosis-sensitive (C57BL/6) mice. In contrast, only the messages encoding SDF-1alpha (now known as Sdf1) and Ccr1 were elevated 26 weeks postirradiation in fibrosis-resistant (C3H/HeJ) mice. Our results point to the CC and CCR family members as the predominant chemokine responders during the development of fibrosis. These studies suggest that monocyte/macrophage and lymphocyte recruitment and activation are key components of radiation-induced fibrosis.
Protein Interaction Domains of the Ubiquitin-specific Protease, USP7/HAUSP (2003)

USP7 or HAUSP is a ubiquitin-specific protease in human cells that regulates the turnover of p53 and is bound by at least two viral proteins, the ICP0 protein of herpes simplex type 1 and the EBNA1 protein of Epstein-Barr virus. We have overexpressed and purified USP7 and shown that the purified protein is monomeric and is active for cleaving both a linear ubiquitin substrate and conjugated ubiquitin on EBNA1. Using partial proteolysis of USP7 coupled with matrix-assisted laser desorption ionization time-of-flight mass spectrometry, we showed that USP7 comprises four structural domains; an N-terminal domain known to bind p53, a catalytic domain, and two C-terminal domains. By passing a mixture of USP7 domains over EBNA1 and ICP0 affinity columns, we showed that the N-terminal p53 binding domain was also responsible for the EBNA1 interaction, while the ICP0 binding domain mapped to a C-terminal domain between amino acids 599-801. Tryptophan fluorescence assays showed that an EBNA1 peptide mapping to residues 395-450 was sufficient to bind the USP7 N-terminal domain and did so with a dissociation constant of 0.9-2 microM, whereas p53 peptides spanning the USP7-binding region gave dissociation constants of 9-17 microM in the same assay. In keeping with these relative affinities, gel filtration analyses of the complexes showed that the EBNA1 peptide efficiently competed with the p53 peptide for USP7 binding, suggesting that EBNA1 could affect p53 function in vivo by competing for USP7.
The Treponema pallidum tro Operon Encodes a Multiple Metal Transporter, a Zinc-dependent Transcriptional Repressor, and a Semi-autonomously Expressed Phosphoglycerate Mutase (2003)

The Treponema pallidum tro operon encodes an ABC transporter (TroABCD), a transcriptional repressor (TroR), and the essential glycolytic enzyme phosphoglycerate mutase (Gpm). The apparently discordant observations that the solute binding protein (TroA) binds Zn2+, whereas DNA binding by TroR in vitro is Mn2+-dependent, have generated uncertainty regarding the identities of the ligand(s) and co-repressor(s) of the permease. Moreover, this operonic structure suggests that Gpm expression, and hence glycolysis, the sole source of ATP for the bacterium, would be suspended during TroR-mediated repression. To resolve these discrepancies, we devised an experimental strategy permitting a more direct assessment of Tro operon function and regulation. We report that (i) apo-TroA has identical affinities for Zn2+ and Mn2+; (ii) the Tro transporter expressed in Escherichia coli imports Zn2+, Mn2+, and possibly iron; (iii) TroR represses transporter expression in E. coli at significantly lower concentrations of Zn2+ than of Mn2+; and (iv) TroR-mediated repression causes a disproportionately greater down-regulation of the transporter genes than of gpm. The much higher concentrations of Zn2+ than of Mn2+ in human body fluids suggests that Zn2+ is both the primary substrate and co-repressor of the permease in vivo. Our data also indicate that Gpm expression and, therefore, glycolysis would not be abrogated when T. pallidum encounters high Zn2+ levels.
Transcription factor CP2 is essential for lens‐specific expression of the chicken αA‐crystallin gene (1998)

We have shown that the tetrameric transcription factor cCP2 is essential for lens-specific transcription of the chicken alphaA-crystallin gene, although it is ubiquitously expressed. We propose a model where cCP2 cooperates with a putative lens-specific factor which binds to LSE.
Nasal vaccination with a proteosome-based adjuvant and glatiramer acetate clears β-amyloid in a mouse model of Alzheimer disease (2005)

Amyloid beta-peptide (Abeta) appears to play a key pathogenic role in Alzheimer disease (AD). Immune therapy in mouse models of AD via Abeta immunization or passive administration of Abeta antibodies markedly reduces Abeta levels and reverses behavioral impairment. However, a human trial of Abeta immunization led to meningoencephalitis in some patients and was discontinued. Here we show that nasal vaccination with a proteosome-based adjuvant that is well tolerated in humans plus glatiramer acetate, an FDA-approved synthetic copolymer used to treat multiple sclerosis, potently decreases Abeta plaques in an AD mouse model. This effect did not require the presence of antibody, as it was observed in B cell-deficient (Ig mu-null) mice. Vaccinated animals developed activated microglia that colocalized with Abeta fibrils, and the extent of microglial activation correlated strongly with the decrease in Abeta fibrils. Activation of microglia and clearing of Abeta occurred with the adjuvant alone, although to a lesser degree. Our results identify a novel approach to immune therapy for AD that involves clearing of Abeta through the utilization of compounds that have been safely tested on or are currently in use in humans.
The role of chemokines in inflammatory joint disease (1996)

Rheumatoid arthritis (RA) is an autoimmune disease characterized by the elicitation and activation of a number of leukocyte populations within both the synovial space and joint tissue. The recruited leukocytes subsequently play an instrumental role in synovial cell proliferation, pannus formation, and bone erosion. Although it is know that leukocytes are important participants in the evolving joint pathology, the mechanism responsible for the successful elicitation of cells to the joint is not clear. A number of studies have identified an association of specific cytokines, including chemokines, with active arthritis, but longitudinal analyses of cytokine expression and the causal role of these mediators have not been defined. Animal models and cell culture systems have proved useful in identifying the expression of various cytokines during the maintenance of chronic joint inflammation. In addition, animal models have provided important information regarding the kinetic production and contribution of specific mediators to the development of experimental arthritis. These studies provide insights into the potential mechanisms for leukocyte involvement in inflammatory joint disease.
Core Commitment Concerns (2012)

You have accessThe ASHA LeaderInbox1 May 2012Core Commitment Concerns Melissa Petersen Melissa Petersen Google Scholar More articles by this author https://doi.org/10.1044/leader.IN2.17062012.2 SectionsAbout ToolsAdd to favorites ShareFacebookTwitterLinked In I am deeply disturbed after reading “Core Commitment” in the April 3ASHA Leader, and seeing ASHA’s uncritical acceptance of the statement that disability accommodations, including IEPs, are supposed “to facilitate a student’s attainment of grade-level academic standards.” Is ASHA aware of the partisan politics surrounding these mandates, or the lunacy of declaring that all children, with the help of an IEP and a teacher held “accountable” to core standards, can achieve grade-level academics? May I introduce you to my students with profound communication disabilities? These kids may never achieve “grade level,” but that does not mean they are not learning or being challenged. The purpose of special education, and IEPs in particular, is to create individual education programs based on the needs of the student. Each plan considers curriculum standards appropriate for that student, but that does not mean expecting grade-level academics from students with profound disabilities. That’s not just unreasonable; it’s downright mean. Students with disabilities learn differently and at different speeds. They deserve to be educated as individuals, not as data-points in our test-crazy quest for the educational master race. Uncritical acceptance of the “core standards” dogma leads to labeling these children as failures if they do not achieve grade level. It is the antithesis of individualized education, and it is wrong. ASHA should be advocating against unrealistic educational policies that label our most vulnerable clients as failures because of their disabilities—not mindlessly validating those dangerous policies in our professional literature. Melissa Petersen Seattle, Washington *Editor’s note: The reader raises important concerns about how the Common Core State Standards apply to students with severe disabilities. The authors plan to address these and similar issues in a subsequent article. Advertising Disclaimer | Advertise With Us Advertising Disclaimer | Advertise With Us Additional Resources FiguresSourcesRelatedDetails Volume 17Issue 6May 2012 Get Permissions Add to your Mendeley library History Published in print: May 1, 2012 Metrics Downloaded 55 times Topicsasha-topicsleader_do_tagleader-topicsasha-article-typesCopyright & Permissions© 2012 American Speech-Language-Hearing AssociationLoading ...
The Catalytic Pathway of Cytochrome P450cam at Atomic Resolution (2000)

Members of the cytochrome P450 superfamily catalyze the addition of molecular oxygen to nonactivated hydrocarbons at physiological temperature-a reaction that requires high temperature to proceed in the absence of a catalyst. Structures were obtained for three intermediates in the hydroxylation reaction of camphor by P450cam with trapping techniques and cryocrystallography. The structure of the ferrous dioxygen adduct of P450cam was determined with 0.91 angstrom wavelength x-rays; irradiation with 1.5 angstrom x-rays results in breakdown of the dioxygen molecule to an intermediate that would be consistent with an oxyferryl species. The structures show conformational changes in several important residues and reveal a network of bound water molecules that may provide the protons needed for the reaction.
Glomerular Endothelial Cell Injury Mediated by Shiga-Like Toxin-1 (1998)

The hemolytic uremic syndrome is an important cause of acute renal failure and is often associated with prior infection with enterotoxigenic strains of Escherichia coli. Significant pathologic changes in the glomerulus include endothelial cell swelling, detachment, and intravascular coagulation. We investigated the potential pathogenetic mechanisms of this disease by exposing cultured rat glomerular endothelial cells to shiga-like toxin 1 (SLT-1). Glomerular endothelial cell viability and protein synthesis were not affected by 10(-9) M SLT-1. Synthesis and release of thromboxane (Tx) A2, measured as the stable metabolite TxB2, and of 12-(S)-HETE were each increased 1.6 +/- 0.1 fold (p < 0.05). No change was observed in the production of PGE2 or 6-keto-PGF1 alpha, the active metabolite of PGI2. SLT-1 (10(-9) M) significantly increased cell retraction and the formation of gaps in the glomerular endothelial cell monolayer for up to 6 h following exposure. A similar effect was seen with 0.1 microM 12-(S)-HETE. SLT-1 and 0.01 microM 12-(S)-HETE also significantly decreased adhesion of glomerular endothelial cells to fibronectin (75 +/- 4 and 65 +/- 2% of control, respectively; p < 0.001) and laminin (81 +/- 5 and 67 +/- 4% of control, respectively; p < 0.01). These results support a role for SLT-1 in the production of the pathologic changes seen in the hemolytic uremic syndrome through stimulation of production of procoagulant, vasoconstrictor arachidonic acid metabolites with potential to produce endothelial injury and through alterations in glomerular endothelial cell adhesion to components of the glomerular basement membrane.
Synaptic plasticity and learning: selective impairment of learning rats and blockade of long-term potentiation in vivo by the N-methyl-D- aspartate receptor antagonist AP5 (1989)

This paper reports a series of 5 experiments concerned with a possible role for N-methyl-D-aspartate (NMDA) receptors in certain types of learning. The results show that chronic intraventricular infusion of the NMDA receptor antagonist D,L-2-amino-5-phosphonopentanoic acid (D,L-AP5) caused an impairment of spatial but not of visual discrimination learning in rats. Such selectivity of the learning impairment occurred despite widespread distribution of the drug throughout the CNS. AP5 sometimes caused a disturbance of sensorimotor function during learning, but one experiment addressing whether this disturbance could be responsible for the spatial learning impairment established that it was statistically independent. Another experiment showed that AP5 did not affect the retention of previously acquired spatial information. These behavioral effects were all obtained with a concentration of AP5 that, in a final study, was found to be sufficient to block hippocampal long-term potentiation (LTP) in vivo without affecting normal synaptic transmission. Taken together, these observations (1) implicate NMDA receptors in certain types of learning, and (2) extend recent work showing that saturation of LTP causes an anterograde spatial amnesia (McNaughton et al., 1986). A preliminary report of parts of this work has been published (Morris et al., 1986a).
Practical protein chemistry : a handbook (1986)

Protein chemistry is a wide field embracing the analysis, synthesis, sequencing and separation of peptides, proteins and individual amino acids. As research work in this subject area increases, an authoritative survey of proven techniques is required. Practical Protein Chemistry is just such a book, designed primarily to be a laboratory handbook for research workers involved with proteins, it will also be of use to undergraduates and their tutors. Each chapter commences with an authoritative introduction to the subject with an account of the practical problems involved. The authors then provide full practical details of methods which they have found to work well, and references to each technique so that they can be researched in the literature with ease. Space necessarily limits the methodologies described - essentially the purification of proteins and peptides, separation of mixtures, determination, sequencing, amino acid analysis, and chemical and enzymatic degradation are all covered. Physico- chemical techniques are largely omitted - but mass spectrometry, X-ray crystallography and electron microscopy which are all important tools for structural studies are included in detail. The final chapter concerns itself with the prediction of peptide and protein structure which may be made from sequencing data.
Quantitative fluorescence imaging determines the absolute number of locked nucleic acid oligonucleotides needed for suppression of target gene expression (2018)

Locked nucleic acid based antisense oligonucleotides (LNA-ASOs) can reach their intracellular RNA targets without delivery modules. Functional cellular uptake involves vesicular accumulation followed by translocation to the cytosol and nucleus. However, it is yet unknown how many LNA-ASO molecules need to be delivered to achieve target knock down. Here we show by quantitative fluorescence imaging combined with LNA-ASO microinjection into the cytosol or unassisted uptake that ∼105 molecules produce >50% knock down of their targets, indicating that a substantial amount of LNA-ASO escapes from endosomes. Microinjected LNA-ASOs redistributed within minutes from the cytosol to the nucleus and remained bound to nuclear components. Together with the fact that RNA levels for a given target are several orders of magnitude lower than the amounts of LNA-ASO, our data indicate that only a minor fraction is available for RNase H1 mediated reduction of target RNA. When non-specific binding sites were blocked by co-administration of non-related LNA-ASOs, the amount of target LNA-ASO required was reduced by an order of magnitude. Therefore, dynamic processes within the nucleus appear to influence the distribution and activity of LNA-ASOs and may represent important parameters for improving their efficacy and potency.
Effect of mode conversion on ultrasonic heating at tissue interfaces (1992)

A number of investigators have observed localized heating by ultrasound beams near impedance discontinuities within tissues. It has been suggested that mode conversion to shear waves at impedance discontinuities and subsequent absorption of these waves in a very small distance was the explanation for this heating. A mathematical model for mode conversion at a plane interface between two viscoelastic media is presented. Longitudinal and shear properties are used to calculate the amount of mode conversion that occurs at muscle-air and muscle-bone interfaces. Shear waves in bone are found to be an important source of heating, but shear waves in the muscle provide a negligible effect on heating at the interface.
Improving Information Extraction by Acquiring External Evidence with Reinforcement Learning (2016)

Most successful information extraction systems operate with access to a large collection of documents. In this work, we explore the task of acquiring and incorporating external evidence to improve extraction accuracy in domains where the amount of training data is scarce. This process entails issuing search queries, extraction from new sources and reconciliation of extracted values, which are repeated until sufficient evidence is collected. We approach the problem using a reinforcement learning framework where our model learns to select optimal actions based on contextual information. We employ a deep Q-network, trained to optimize a reward function that reflects extraction accuracy while penalizing extra effort. Our experiments on two databases -- of shooting incidents, and food adulteration cases -- demonstrate that our system significantly outperforms traditional extractors and a competitive meta-classifier baseline.
Tunable filters using wideband elastic resonators (2013)

Currently, an ultra-wideband resonator is greatly needed to realize a tunable filter with a wide tunable range, because mobile phones with multiple bands and cognitive radio systems require such tunable filters to simplify their circuits. Although tunable filters have been studied using SAW resonators, their tunable range was insufficient for the filters even when wideband SAW resonators with a bandwidth of 17% were used. Therefore, the fabrication of wider-bandwidth resonators has been attempted with the goal of realizing tunable filters with wide tunable ranges. In this study, an SH0- mode plate wave resonator in a 27.5°YX-LiNbO3 plate with an ultra-wide bandwidth of 29.1%, a high impedance ratio of 98 dB, and a high Q (Q(r) = 700 and Q(a) = 720) was realized. Two types of tunable filters were constructed using such SH0-mode resonators and capacitors. As a result, tunable ranges (bands) of 13% to 19% were obtained. The possibility of applying the SH0-mode resonator in the high-frequency gigahertz range is discussed.
Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America (2008)

The Infectious Diseases Society of America (IDSA) continues to view with concern the lean pipeline for novel therapeutics to treat drug-resistant infections, especially those caused by gram-negative pathogens. Infections now occur that are resistant to all current antibacterial options. Although the IDSA is encouraged by the prospect of success for some agents currently in preclinical development, there is an urgent, immediate need for new agents with activity against these panresistant organisms. There is no evidence that this need will be met in the foreseeable future. Furthermore, we remain concerned that the infrastructure for discovering and developing new antibacterials continues to stagnate, thereby risking the future pipeline of antibacterial drugs. The IDSA proposed solutions in its 2004 policy report, "Bad Bugs, No Drugs: As Antibiotic R&D Stagnates, a Public Health Crisis Brews," and recently issued a "Call to Action" to provide an update on the scope of the problem and the proposed solutions. A primary objective of these periodic reports is to encourage a community and legislative response to establish greater financial parity between the antimicrobial development and the development of other drugs. Although recent actions of the Food and Drug Administration and the 110th US Congress present a glimmer of hope, significant uncertainly remains. Now, more than ever, it is essential to create a robust and sustainable antibacterial research and development infrastructure--one that can respond to current antibacterial resistance now and anticipate evolving resistance. This challenge requires that industry, academia, the National Institutes of Health, the Food and Drug Administration, the Centers for Disease Control and Prevention, the US Department of Defense, and the new Biomedical Advanced Research and Development Authority at the Department of Health and Human Services work productively together. This report provides an update on potentially effective antibacterial drugs in the late-stage development pipeline, in the hope of encouraging such collaborative action.