gebhart/patrepeval huggingface dataset:
gC1qR/p33 Blockade ReducesStaphylococcus aureusColonization of Target Tissues in an Animal Model of Infective Endocarditis (2006)

gC1qR/p33 (gC1qR) is a ubiquitously expressed cellular protein that is also found in plasma and the extracellular matrix. In addition to its role in modulating the activation of complement and kinin cascades, gC1qR has been identified as a putative host ligand for endovascular pathogens, including Staphylococcus aureus. The present study provides evidence of the ability of soluble gC1qR to enhance S. aureus-fibrinogen interactions via simultaneously binding fibrinogen and S. aureus. This interaction was inhibited in vitro by two monoclonal antibodies (MAbs 74.5.2 and 60.11) recognizing distinct structural and functional domains of gC1qR. To evaluate the in vivo role of gC1qR, MAbs 74.5.2 and 60.11 were used in an experimental rat model of S. aureus endocarditis. Each MAb (100 mg/kg of body weight, given intraperitoneally) reached sustained (>60 h) and high (100 to 200 microg/ml) serum levels. Prophylaxis with MAb 60.11 or 74.5.2 caused substantial reductions in S. aureus colonization of aortic valves, kidneys, and the spleen compared to untreated controls. However, only MAb 74.5.2 prophylaxis therapy reached statistical significance, and only sera from animals protected with MAb 74.5.2 inhibited gC1qR-mediated S. aureus interactions with fibrinogen. Although not statistically significant, the reductions in bacterial colonization achieved with MAb 60.11 alone and in combination with MAb 74.5.2 (versus MAb 74.5.2 alone) suggest that there are effects of gC1qR blockade on S. aureus infective endocarditis in addition to blocking gC1qR-mediated S. aureus binding to fibrinogen. Such impacts may include direct modulation of complement (MAb 60.11) and kinin cascades (MAb 74.5.2) and/or activation of immune and inflammatory responses via localized immune complex formation.
Regulation of TNF‐α‐induced eotaxin release from cultured human airway smooth muscle cells by β 2 ‐agonists and corticosteroids (2001)

Eotaxin is a potent eosinophil chemoattractant that contributes to the eosinophilia seen in asthma and other allergic disorders. Recent studies have identified human airway smooth muscle (HASM) as a rich source of eotaxin, but the factors regulating its production are poorly understood. Here we describe for the first time that beta2-agonists can inhibit cytokine-induced eotaxin release. We found that TNF-alpha stimulated eotaxin release (assayed by ELISA) from HASM cells and that the release was partially inhibited by salbutamol and salmeterol. The effect of beta2-agonists was mimicked by forskolin and 8-bromo-cAMP and potentiated by the cAMP-dependent phosphodiesterase inhibitor rolipram, suggesting that it is cAMP dependent. We also found that the cAMP inhibition was likely at the transcription stage, although experiments with the PKA inhibitors H-89 and Rp-cAMP or the PKG inhibitor KT5823 suggested that none of these kinases was involved. Partial inhibition of eotaxin release was also seen with the corticosteroids dexamethasone and fluticasone. The combined use of beta2-agonists, rolipram, and steroids abolished TNF-alpha-induced eotaxin release. These results suggest that the combination of a beta2-agonist, PDE inhibitor, and a corticosteroid may have additive beneficial effects in the treatment of the eosinophilia associated with asthma and other allergic diseases.
Considerations for patients with obstructive sleep apnea undergoing ambulatory surgery (2011)

The recent publications indicated that the majority of OSA patients may be done as ambulatory surgical patients with few adverse events. However, it may not be safe to do patients with severe OSA requiring postoperative narcotics as ambulatory surgical patients.
The future of microprocessors (1996)

Before making statements about microprocessor trends 10 years out-Micro 2006-it might be useful to revisit our past statements (Gelsinger et al. (1989, 1991)) about the microprocessor of today and the microprocessor of 2000. Then we can see where we have been right and where wrong. This retrospective will reveal important trends that promise to give some insight into the microprocessor of the next decade.
Structure of plant and fungal peroxidases (1992)

Conference Article| May 01 1992 Structure of plant and fungal peroxidases Karen G. Welinder; Karen G. Welinder 1Institute of Biochemical Genetics, University of Copenhagen, Øster Farimagsgade 2A, DK-1353 Copenhagen K, Denmark Search for other works by this author on: This Site PubMed Google Scholar J. Matthew Mauro; J. Matthew Mauro 2Center for Advanced Research in Biotechnology, 9600 Gudelsky Drive, Rockville MD 20850, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar Leif Nørskov-Lauritsen Leif Nørskov-Lauritsen 3Novo Nordisk A/S, Novo Alle, 2880 Bagsværd, Denmark Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1992) 20 (2): 337–340. https://doi.org/10.1042/bst0200337 Article history Received: December 18 1991 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation Karen G. Welinder, J. Matthew Mauro, Leif Nørskov-Lauritsen; Structure of plant and fungal peroxidases. Biochem Soc Trans 1 May 1992; 20 (2): 337–340. doi: https://doi.org/10.1042/bst0200337 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: CCP, cytochrome c peroxidase, HRP, horseradish peroxidase This content is only available as a PDF. © 1992 Biochemical Society1992 Article PDF first page preview Close Modal You do not currently have access to this content.
Bax directly induces release of cytochrome c from isolated mitochondria (1998)

Bax is a pro-apoptotic member of the Bcl-2 protein family that resides in the outer mitochondrial membrane. It is controversial whether Bax promotes cell death directly through its putative function as a channel protein versus indirectly by inhibiting cellular regulators of the cell death proteases (caspases). We show here that addition of submicromolar amounts of recombinant Bax protein to isolated mitochondria can induce cytochrome c (Cyt c) release, whereas a peptide representing the Bax BH3 domain was inactive. When placed into purified cytosol, neither mitochondria nor Bax individually induced proteolytic processing and activation of caspases. In contrast, the combination of Bax and mitochondria triggered release of Cyt c from mitochondria and induced caspase activation in cytosols. Supernatants from Bax-treated mitochondria also induced caspase processing and activation. Recombinant Bcl-XL protein abrogated Bax-induced release of Cyt c from isolated mitochondria and prevented caspase activation. In contrast, the broad-specificity caspase inhibitor benzyloxycarbonyl-valinyl-alaninyl-aspartyl-(0-methyl)- fluoromethylketone (zVAD-fmk) and the caspase-inhibiting protein X-IAP had no effect on Bax-induced release of Cyt c from mitochondria in vitro but prevented the subsequent activation of caspases in cytosolic extracts. Unlike Ca2+, a classical inducer of mitochondrial permeability transition, Bax did not induce swelling of mitochondria in vitro. Because the organellar swelling caused by permeability transition causes outer membrane rupture, the findings, therefore, dissociate these two events, implying that Bax uses an alternative mechanism for triggering release of Cyt c from mitochondria.
Toll-like receptor 9–induced type I IFN protects mice from experimental colitis (2005)

Experimental colitis is mediated by inflammatory or dysregulated immune responses to microbial factors of the gastrointestinal tract. In this study we observed that administration of Toll-like receptor 9 (TLR9) agonists suppressed the severity of experimental colitis in RAG1-/- but not in SCID mice. This differential responsiveness between phenotypically similar but genetically distinct animals was related to a partial blockade in TLR9 signaling and defective production of type I IFN (i.e., IFN-alpha/beta) in SCID mice upon TLR9 stimulation. The addition of neutralization antibodies against type I IFN abolished the antiinflammatory effects induced by TLR9 agonists, whereas the administration of recombinant IFN-beta mimicked the antiinflammatory effects induced by TLR9 agonists in this model. Furthermore, mice deficient in the IFN-alpha/beta receptor exhibited more severe colitis than wild-type mice did upon induction of experimental colitis. These results indicate that TLR9-triggered type I IFN has antiinflammatory functions in colitis. They also underscore the important protective role of type I IFN in intestinal homeostasis and suggest that strategies to modulate innate immunity may be of therapeutic value for the treatment of intestinal inflammatory conditions.
A Deep Hierarchical Approach to Lifelong Learning in Minecraft (2017)

We propose a lifelong learning system that has the ability to reuse and transfer knowledge from one task to another while efficiently retaining the previously learned knowledge-base. Knowledge is transferred by learning reusable skills to solve tasks in Minecraft, a popular video game which is an unsolved and high-dimensional lifelong learning problem. These reusable skills, which we refer to as Deep Skill Networks, are then incorporated into our novel Hierarchical Deep Reinforcement Learning Network (H-DRLN) architecture using two techniques: (1) a deep skill array and (2) skill distillation, our novel variation of policy distillation (Rusu et. al. 2015) for learning skills. Skill distillation enables the H-DRLN to efficiently retain knowledge and therefore scale in lifelong learning, by accumulating knowledge and encapsulating multiple reusable skills into a single distilled network. The H-DRLN exhibits superior performance and lower learning sample complexity compared to the regular Deep Q Network (Mnih et. al. 2015) in sub-domains of Minecraft.
List of Drugs in Development for Neurodegenerative Diseases (2004)

Background/Aims: Alzheimer’s disease (AD) is characterized by extracellular Aβ peptide deposition originating from amyloid precursor protein cleavage and intracellular neurofibrilla
An Ephrin Mimetic Peptide That Selectively Targets the EphA2 Receptor (2002)

Eph receptor tyrosine kinases represent promising disease targets because they are differentially expressed in pathologic versus normal tissues. The EphA2 receptor is up-regulated in transformed cells and tumor vasculature where it likely contributes to cancer pathogenesis. To exploit EphA2 as a therapeutic target, we used phage display to identify two related peptides that bind selectively to EphA2 with high affinity (submicromolar K(D) values). The peptides target the ligand-binding domain of EphA2 and compete with ephrin ligands for binding. Remarkably, one of the peptides has ephrin-like activity in that it stimulates EphA2 tyrosine phosphorylation and signaling. Furthermore, this peptide can deliver phage particles to endothelial and tumor cells expressing EphA2. In contrast, peptides corresponding to receptor-interacting portions of ephrin ligands bind weakly and promiscuously to many Eph receptors. Bioactive ephrin mimetic peptides could be used to selectively deliver agents to Eph receptor-expressing tissues and modify Eph signaling in therapies for cancer, pathological angiogenesis, and nerve regeneration.
Summary of the Workshop on Future Directions in Discovery and Development of Therapeutic Agents for Opportunistic Infections Associated with AIDS (1991)

Journal Article Summary of the Workshop on Future Directions in Discovery and Development of Therapeutic Agents for Opportunistic Infections Associated with AIDS Get access Barbara E. Laughon, Barbara E. Laughon Search for other works by this author on: Oxford Academic PubMed Google Scholar H. S. Allaudeen, H. S. Allaudeen Search for other works by this author on: Oxford Academic PubMed Google Scholar Jeffrey M. Becker, Jeffrey M. Becker Search for other works by this author on: Oxford Academic PubMed Google Scholar William L. Current, William L. Current Search for other works by this author on: Oxford Academic PubMed Google Scholar Judith Feinberg, Judith Feinberg Search for other works by this author on: Oxford Academic PubMed Google Scholar Jacob K. Frenkel, Jacob K. Frenkel Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard Hafner, Richard Hafner Search for other works by this author on: Oxford Academic PubMed Google Scholar Walter T. Hughes, Walter T. Hughes Search for other works by this author on: Oxford Academic PubMed Google Scholar Catherine A. Laughlin, Catherine A. Laughlin Search for other works by this author on: Oxford Academic PubMed Google Scholar Joel D. Meyers, Joel D. Meyers Search for other works by this author on: Oxford Academic PubMed Google Scholar ... Show more Lewis K. Schrager, Lewis K. Schrager Search for other works by this author on: Oxford Academic PubMed Google Scholar Lowell S. Young Lowell S. Young Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 164, Issue 2, August 1991, Pages 244–251, https://doi.org/10.1093/infdis/164.2.244 Published: 01 August 1991 Article history Revision received: 09 April 1990 Received: 26 November 1990 Published: 01 August 1991
Screening and application of ATRP catalysts utilizing an automated synthesizer (2002)

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Biosynthesis of the human transferrin receptor in cultured cells. (1981)

The biosynthesis and degradation of the cell surface transferrin receptor has been investigated. The receptor is a glycoprotein, and evidence is presented that the mature receptor contains both complex and high mannose N-asparagine-linked oligosaccharides that are synthesized via a common high mannose intermediate as previously described for other glycoproteins. It is shown that fatty acid is associated with only the mature form of the receptor and that addition of fatty acid to the receptor and that addition of fatty acid to the receptor can occur as long as 48 h after synthesis. Glycosylation is not an absolute requirement for the receptor to act as acceptor for fatty acid, nor for transport to the cell surface, although the efficiency of both processes may be reduced in tunicamycin-treated cells. The protein moiety of the transferrin receptor is degraded with a half-life of approximately 60 h.
A Doppler parameters estimation technique for squint SAR imaging (2008)

An essential part of SAR processing is the estimation of the Doppler parameters of the received data-the Doppler centroid and the Doppler frequency rate. This paper proposes a Doppler parameters estimation technique for squint SAR imaging, where the estimation of the Doppler frequency rate is dependent on that of the Doppler centroid. It estimates the Doppler centroid based on the relationship of the Doppler centroid and the range cell migration (RCM), and estimates the Doppler frequency rate using an improved Radon ambiguity transform (RAT) method based on the data aligned according to the RCM trajectory. This technique needs no prior knowledge of the radar platform velocity and the beam squint angle, and shows good performance of estimating the Doppler parameters. Simulation results demonstrate the validity of the method.
Relationship between Folding and Function in a Sequence-Specific Miniature DNA-Binding Protein (2005)

Previously, we have described a miniature protein-based approach to the design of molecules that bind DNA or protein surfaces with high affinity and specificity. In this approach, the small, well-folded protein avian pancreatic polypeptide acts as a scaffold to present and stabilize an alpha-helical or PPII-helical recognition epitope. The first miniature protein designed in this way, a molecule called p007, presents the alpha-helical recognition epitope found on the bZIP protein GCN4 and binds DNA with nanomolar affinity and exceptional specificity. In this work we use alanine-scanning mutagenesis to explore the contributions of 29 p007 residues to DNA affinity, specificity, and secondary structure. Virtually every residue within the p007 alpha-helix, and most residues within the p007 PPII helix, contribute to both DNA affinity and specificity. These residues include those introduced to make specific and nonspecific DNA contacts, as well as those that complete the miniature protein core. Moreover, there exists a direct correlation between the affinity of a p007 variant for specific DNA and the ability of that variant to select for specific DNA over nonspecific DNA. Although we observe no correlation between alpha-helicity and affinity, we observe a limited correlation between alpha-helicity and sequence specificity that emphasizes the role of coupled binding/folding in the function of p007. Our results imply that formation of a highly evolved set of protein.DNA contacts in the context of a well-packed hydrophobic core, and not the extent of intrinsic alpha-helical structure, is the primary determinant of p007 function.
Lysyl oxidase gene expression in the stromal reaction to in situ and invasive ductal breast carcinoma. (1997)

Lysyl oxidase is involved in the main pathway of collagen and elastin cross-linking: it has a role in the maturation of fibrillar matrix proteins in fibrosing processes and dictates their stability against metalloproteases. The stromal reaction patterns in ductal breast carcinoma are known to be morphologically varied. This has raised the hypothesis that there might be a differential expression of the lysyl oxidase gene as a function of stromal reaction pattern. The present study investigates this potential correlation and the role of matrix protein cross-linking in stromal differentiation. Lysyl oxidase was detected by immunohistochemistry and lysyl oxidase gene expression by in situ hybridization. Maximal expression was observed in myofibroblasts and myoepithelial cells around in situ tumors and in the reactive fibrosis facing the invasion front of infiltrating tumors. The lysyl oxidase substrates were observed in parallel, resulting in the stabilization of a scar-like peritumor barrier. In contrast, a lack of lysyl oxidase was associated with the loose or scirrhous stroma accompanying invading tumors; here, in situ hybridization revealed type I collagen synthesis, resulting in the deposition of non-cross-linked matrix proteins susceptible to degradation. The early development of a cross-linked matrix around ductal breast carcinoma suggests a possible bost defense mechanism, whereas the synchronous or late stromal reaction lacking lysyl oxidase favors tumor dispersion.
A Reversible Defect in Natural Killer T Cell Function Characterizes the Progression of Premalignant to Malignant Multiple Myeloma (2003)

We studied the function of antitumor T and natural killer T (NKT) cells from the blood and tumor bed in 23 patients with premalignant gammopathy, nonprogressive myeloma, or progressive multiple myeloma. We show that antitumor killer T cells can be detected in patients with both progressive or nonprogressive myeloma. V alpha 24+V beta 11+ invariant NKT cells are detectable in the blood and tumor bed of all cohorts. However, freshly isolated NKT cells from both the blood and tumor bed of patients with progressive disease, but not nonprogressive myeloma or premalignant gammopathy, have a marked deficiency of ligand-dependent interferon-gamma production. This functional defect can be overcome in vitro using dendritic cells pulsed with the NKT ligand, alpha-galactosylceramide (alpha-GalCer). Fresh myeloma cells express CD1d, and can be efficiently killed by autologous NKT cells. We hypothesize that presentation of tumor derived glycolipids by myeloma cells leads to NKT dysfunction in vivo. These data demonstrate that clinical progression in patients with monoclonal gammopathies is associated with an acquired but potentially reversible defect in NKT cell function and support the possibility that these innate lymphocytes play a role in controlling the malignant growth of this incurable B cell tumor in patients.
Dendritic cells exposed in vitro to TGF-beta1 ameliorate experimental autoimmune myasthenia gravis (2002)

Experimental autoimmune myasthenia gravis (EAMG) is an animal model for human myasthenia gravis (MG), characterized by an autoaggressive T-cell-dependent antibody-mediated immune response directed against the acetylcholine receptor (AChR) of the neuromuscular junction. Dendritic cells (DC) are unique antigen-presenting cells which control T- and B-cell functions and induce immunity or tolerance. Here, we demonstrate that DC exposed to TGF-β1 in vitro mediate protection against EAMG. Freshly prepared DC from spleen of healthy rats were exposed to TGF-β1 in vitro for 48 h, and administered subcutaneously to Lewis rats (2 × 106DC/rat) on day 5 post immunization with AChR in Freund’s complete adjuvant. Control EAMG rats were injected in parallel with untreated DC (naive DC) or PBS. Lewis rats receiving TGF-β1-exposed DC developed very mild symptoms of EAMG without loss of body weight compared with control EAMG rats receiving naive DC or PBS. This effect of TGF-β1-exposed DC was associated with augmented spontaneous and AChR-induced proliferation, IFN-γ and NO production, and decreased levels of anti-AChR antibody-secreting cells. Autologous DC exposed in vitro to TGF-β1 could represent a new opportunity for DC-based immunotherapy of antibody-mediated autoimmune diseases.
High-throughput data compressor designs using content addressable memory (2002)

This paper presents a novel VLSI architecture for high-speed data compressor designs which implement the well-known LZ77 algorithm. The architecture mainly consists of three units, namely content addressable memory, match logic, and output stage. The content address memory generates a set of hit signals which identify those positions whose symbols in a specified window are the same as input symbol. These hits signals are then passed to the match logic which determines one matched stream and its match length and location in the window to form the kernel of compressed data. These two items are then passed to the output stage for packetization before sent out. By trading off hardware complexity and compression ratio, 2KB window size and adjustable maximum match length are considered in our proto-type VLSI chip. Simulation results show that, based on a 0.8 /spl mu/m CMOS process technology, clock speed up to 50 MHz can be achieved. This implies that the developing data compressor chip can handle many real-life applications such as in video coding and high-speed data storage systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Various factors (allergen nature, mouse strain, CpG/recombinant protein expressed) influence the immune response elicited by genetic immunization (2003)

Immune responses after genetic immunization are strongly influenced by the nature of the allergen, the mouse strain, and the ratio of CpG to recombinant protein expressed.