gebhart/patrepeval huggingface dataset:
A key angiogenic role of monocyte chemoattractant protein-1 in hemangioendothelioma proliferation (2004)

Angiomatous lesions are common in infants and children. Hemangioendotheliomas (HE) represent one type of these lesions. Endothelial cell proliferation and the development of vascular/blood cell-filled spaces are inherent in the growth of HE. Therefore, understanding mechanisms that regulate the proliferation of these lesions should provide key insight into mechanisms regulating angiogenesis. A murine model was used to test the significance of monocyte chemoattractant protein (MCP)-1 in HE proliferation. EOMA cells, a cell line derived from a spontaneously arising murine HE, generate these lesions with 100% efficiency when injected subcutaneously into syngeneic mice. MCP-1 produced by EOMA cells recruit macrophages, which were shown to induce angiogenic behavior in EOMA cells by stimulating transwell migration and inducing sprout formation on type I collagen gels. When EOMA cells were injected into MCP-1(-/-) mice, only 50% of the mice developed tumors, presumably because the low levels of MCP-1 expressed by the injected EOMA cells were enough to overcome any host deficits of this chemokine. When EOMA cells were coinjected with a neutralizing antibody to MCP-1, tumors failed to develop in any of the treated mice, including syngeneic 129P3, C57Bl/6 (wild type), and MCP-1(-/-). These results present the first evidence that MCP-1 is required for HE proliferation and may promote the growth of these lesions by stimulating angiogenic behavior of endothelial cells. This study has produced the first in vivo evidence of a complete response for any neoplasm, specifically a vascular proliferative lesion, to anti-MCP-1 therapy in animals with intact immune systems.
Rat blood neutrophils express very late antigen 4 and it mediates migration to arthritic joint and dermal inflammation. (1996)

Blood neutrophils contribute to joint injury in human and experimental models of arthritis. Neutrophil migration out of the blood in joint inflammation involves both the CD18 (beta2) integrins and a CD18 integrin-independent pathway. To investigate this migration, radiolabeled rat blood neutrophils were used to measure neutrophil accumulation in the inflamed joints of rats with adjuvant arthritis and the role of leukocyte integrins in migration to these joints and to dermal inflammation was determined. Neutrophils migrated rapidly (<2 h) to the inflamed joints 14-18 d after immunization with adjuvant. Blocking monoclonal antibodies (mAbs) to both LFA-1 and Mac-1 together, as well as a mAb to CD18, inhibited neutrophil accumulation in the inflamed joints by 50-75%. However, migration to dermal inflammation induced by C5a(des Arg)' tumor necrosis factor alpha, lipopolysaccharide, and poly-inosine:cytosine was inhibited by approximately 90%. Flow cytometry revealed the expression of low levels of very late antigen 4 (VLA-4) on nearly all rat blood neutrophils. Treatment with anti-VLA-4 plus anti-LFA-1 but neither mAb alone, strongly (60-75%) inhibited neutrophil accumulation in arthritic joints. This mAb combination also inhibited neutrophil migration to dermal inflammatory reactions by 30-70%. Blocking VLA-4 together with the CD18 integrins inhibited neutrophil accumulation by 95-99%, virtually abolishing neutrophil accumulation in cutaneous inflammation. A similar blockade of VLA-4 and CD18 decreased neutrophil accumulation in the inflamed joints by 70-83%, but a significant portion of the neutrophil accumulation to these joints still remained. In conclusion, rat blood neutrophils express functional VLA-4 that can mediate neutrophil migration to both inflamed joints and dermal inflammatory sites. VLA-4 appears to be able to substitute for LFA-1 in this migration and is particularly important for accumulation in inflamed joints. However, there exists an additional CD18- and VLA-4-independent pathway of neutrophil migration to arthritic joints that is not involved in acute dermal inflammation.
Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by αvβ3 and α5β1 integrins (2003)

Tumstatin and endostatin are two inhibitors of angiogenesis derived from precursor human collagen molecules known as alpha 3 chain of type IV collagen and alpha1 chain of type XVIII collagen, respectively. Although both these inhibitors are noncollagenous (NC1) domain fragments of collagens, they only share a 14% amino acid homology. In the present study we evaluated the functional receptors, mechanism of action, and intracellular signaling induced by these two collagen-derived inhibitors. Human tumstatin prevents angiogenesis via inhibition of endothelial cell proliferation and promotion of apoptosis with no effect on migration, whereas human endostatin prevents endothelial cell migration with no effect on proliferation. We demonstrate that human tumstatin binds to alpha v beta 3 integrin in a vitronectin/fibronectin/RGD cyclic peptide independent manner, whereas human endostatin competes with fibronectin/RGD cyclic peptide to bind alpha 5 beta 1 integrin. The activity of human tumstatin is mediated by alpha v beta 3 integrin, whereas the activity of human endostatin is mediated by alpha 5 beta 1 integrin. Additionally, although human tumstatin binding to alpha v beta 3 integrin leads to the inhibition of Cap-dependent translation (protein synthesis) mediated by focal adhesion kinase/phosphatidylinositol 3-kinase/Akt/mTOR/4E-BP1 pathway, human endostatin binding to alpha 5 beta 1 integrin leads to the inhibition of focal adhesion kinase/c-Raf/MEK1/2/p38/ERK1 mitogen-activated protein kinase pathway, with no effect on phosphatidylinositol 3-kinase/Akt/mTOR/4E-BP1 and Cap-dependent translation. Collectively, such distinct properties of human tumstatin and human endostatin provide the first insight into their diverse antiangiogenic actions and argue for combining them for targeting tumor angiogenesis.
The Effect and Timing of Food on the Pharmacokinetics and Pharmacodynamics of TAK-390MR (Modified Release): Evidence for Dosing Flexibility (2007)

Purpose: TAK-390MR is a proton pump inhibitor that employs a modified release technology designed to provide prolonged plasma concentrations of TAK-390 following once daily oral dosing. This study evaluated the effect and timing of food on the pharmacokinetics (PK) and pharmacodynamics (PD) of TAK-390 after a single 90 mg dose of TAK-390MR. Methods: Phase 1, open-label, single-dose, randomized, 4-way crossover study. Forty-eight healthy subjects (18–55 years) received a single oral dose of TAK-390MR 90 mg in the fasted state (A) and 3 fed states (30 minutes after the start of a high-fat breakfast [B], 5 and 30 minutes before a high-fat breakfast [C, D]). Serial blood samples were obtained for up to 24 hours postdose. To adjust for the effect of food on pH, baseline as well as postdose 24-h intragastric pH monitoring was performed for each regimen. Plasma concentrations of TAK-390 were determined using a validated LC-MS/MS assay; PK parameters were estimated using noncompartmental methods. PD parameters were calculated as the mean pH and% time pH > 4 over 24-h. The effect of food and the timing of food on TAK-390 PK and PD were assessed and pairwise comparisons were conducted between the fasting and fed regimens. The 90% confidence intervals (CI) for relative bioavailability between 2 regimens were computed and a conclusion of no difference was made if the 90% CI for the ratios of TAK-390 Cmax and AUCs from 2 regimens were within 0.80 and 1.25. Changes in PD parameters from baseline to postdose were also assessed and pairwise comparisons between the fed regimens to the fasting regimen were also performed, with a test deemed statistically significant if the P-value was ≤0.05. Results: Forty-six subjects completed all regimens. TAK-390MR given under 3 fed conditions resulted in a modest and statistically significant increase in Cmax and AUCs (9–31%) relative to fasting. No statistically significant difference for mean intragastric pH was observed among the dosing regimens in change from baseline over the total 24-h postdose interval. Although a statistically significant greater change from baseline was seen in% time pH > 4 for both regimens A and D compared to regimen B, the small differences are not likely to be relevant. Conclusion: Although TAK-390MR administered under various fed conditions compared to the fasted state had a statistically significant effect on the PK of TAK-390, the intragastric pH results indicate that TAK-390MR can be administered without regard to food.
Peptide transporter (TAP-1 and TAP-2)-independent endogenous processing of Epstein-Barr virus (EBV) latent membrane protein 2A: implications for cytotoxic T-lymphocyte control of EBV-associated malignancies (1996)

Major histocompatibility [correction of histocampatability] complex (MHC) class I-restricted cytotoxic T lymphocytes (CTLs) recognizing Epstein-Barr virus (EBV) latent antigens play a pivotal role in restricting the proliferation of EBV-infected normal B cells. However, it is now well established that most of the EBV-associated malignancies escape this potent CTL response in vivo. This resistance to immune surveillance is not due to an obvious CTL dysfunction but has been partly attributed to the down-regulation of the peptide transporters, TAP-1 and TAP-2, thus restricting the endogenous loading of MHC class I molecules with peptides derived from viral nuclear antigens. In the present study we have explored the possibility that EBV latent membrane protein 2A (LMP2A), which is often expressed in many of the EBV-associated malignancies, such as nasopharyngeal carcinoma and Hodgkin's disease tumors, can be endogenously processed through an alternative, TAP-1- and TAP-2-independent pathway. The data presented in this study clearly demonstrate not only that LMP2A can be processed by a TAP-independent mechanism but also that tumor cells with down-regulated TAP expression can be efficiently recognized by LMP2A-specific T cells following infection with recombinant vaccinia virus encoding this protein. We propose that since LMP2A is a membrane protein, it is directly translocated into the secretory pathway and the processing enzymes present in the endoplasmic reticulum are capable of generating the relevant peptide epitopes for MHC binding. The present finding of TAP-1- and TAP-2-independent presentation of LMP2A epitopes suggests a novel mechanism for immune targeting of EBV-positive malignancies, such as nasopharyngeal carcinoma and Hodgkin's disease tumors.
Freeform drop-on-demand laser printing of 3D alginate and cellular constructs (2015)

Laser printing is an orifice-free printing approach and has been investigated for the printing of two-dimensional patterns and simple three-dimensional (3D) constructs. To demonstrate the potential of laser printing as an effective bioprinting technique, both straight and Y-shaped tubes have been freeform printed using two different bioinks: 8% alginate solution and 2% alginate-based mouse fibroblast suspension. It has been demonstrated that 3D cellular tubes, including constructs with bifurcated overhang structures, can be adequately fabricated under optimal printing conditions. The post-printing cell viabilities immediately after printing as well as after 24 h incubation are above 60% for printed straight and Y-shaped fibroblast tubes. During fabrication, overhang and spanning structures can be printed using a dual-purpose crosslinking solution, which also functions as a support material. The advancement distance of gelation reaction front after a cycle time of the receiving platform downward motion should be estimated for experimental planning. The optimal downward movement step size of receiving platform should be chosen to be equal to the height of ungelled portion of a previously printed layer.
On Multiplicative Integration with Recurrent Neural Networks (2016)

We introduce a general and simple structural design called Multiplicative Integration (MI) to improve recurrent neural networks (RNNs). MI changes the way in which information from difference sources flows and is integrated in the computational building block of an RNN, while introducing almost no extra parameters. The new structure can be easily embedded into many popular RNN models, including LSTMs and GRUs. We empirically analyze its learning behaviour and conduct evaluations on several tasks using different RNN models. Our experimental results demonstrate that Multiplicative Integration can provide a substantial performance boost over many of the existing RNN models.
Human CD34+ HLA-DR- bone marrow cells contain progenitor cells capable of self-renewal, multilineage differentiation, and long-term in vitro hematopoiesis. (1991)

Human bone marrow cells expressing CD34 but not HLA-DR were isolated by immunofluorescence flow cytometric cell sorting. These cells contained a hematopoietic cell (CFU-B1) capable of producing, in an in vitro semisolid culture system, blast-cell-containing colonies, which possessed the capacity for self-renewal and commitment to multipotential differentiation. In addition, CD34+ HLA-DR- marrow cells contained primitive megakaryocyte progenitor cells, the burst-forming unit-megakaryocyte (BFU-MK). A subset of CD34+ HLA-DR- marrow cells lacking the expression of CD15 and CD71 was obtained by flow cytometric cell sorting and was capable of sustaining in vitro hematopoiesis in suspension culture for up to 8 weeks in the absence of a preestablished adherent marrow cell layer. The combination of IL-3 + IL-1 alpha and IL-3 + IL-6 sustained proliferation of these cells for 8 weeks, induced maximal cellular expansion, and increased the numbers of assayable progenitor cells. These studies demonstrate that human CD34+ HLA-DR- marrow cells and their subsets contain primitive multipotential hematopoietic cells capable of self-renewal and of differentiation into multiple hematopoietic lineages.
Bayes estimation on parameters of the single-class classifier (1976)

Normal procedures used for designing a Bayes classifier to classify wheat as the major crop of interest require not only training samples of wheat but also those of nonwheat. Therefore, ground truth must be available for the class of interest plus all confusion classes. The single-class Bayes classifier classifies data into the class of interest or the class "other" but requires training samples only from the class of interest. This paper will present a procedure for Bayes estimation on the µi, Σi, qi (i.e., mean vector, covariance matrix, and a priori probability) of the single-class classifier using labeled samples from the class of interest and unlabeled samples drawn from p(x). The procedure used to derive µi, Σi, and qi is to minimize mL', which is the mean square error of the Bayes decision function of the single-class classifier.
A two-sensor array blind beamformer for direct sequence spread spectrum communications (1999)

We present an efficient blind beamformer dedicated to the problem of interference mitigation in direct sequence spread spectrum (DSSS) communication systems using a two-sensor array. A closed-form solution for the blind identification of the communication channel is derived by exploiting the temporal properties of the desired signal and the interference. The optimal beamformer is derived from the maximization of the signal-to-interference and noise ratio (SINR) at the output of the receiver in terms of the blindly estimated channel coefficients. Three structures of the DSSS receiver are presented. One structure consists of the blind beamformer followed by the spread spectrum demodulator. The other two structures consist of the spread spectrum demodulator followed by the blind beamformer. The performance of these structures is discussed in terms of the achieved SINR and the computational cost. Simulation results are provided to illustrate the effectiveness of the proposed blind beamformers in interference excision.
A gene for episodic ataxia/myokymia maps to chromosome 12p13. (1994)

Episodic ataxia (EA) is a rare, familial disorder producing attacks of generalized ataxia, with normal or near-normal neurological function between attacks. Families with autosomal dominant EA represent at least two distinct clinical syndromes. One clinical type of EA (MIM 160120) includes individuals who have episodes of ataxia and dysarthria lasting seconds to minutes. In addition, myokymia (rippling of muscles, diagnosable by electromyography) is evident during and between attacks. Since K+ channel genes are candidate genes for EA, we tested markers near known K+ channel genes for linkage. Using a group of Genethon markers from one such region--chromosome 12p--we found evidence of linkage in four EA/myokymia families. A maximum combined lod score of 13.6 was obtained at theta = 0, with the marker D12S99. A human Ca++ channel gene, CACNL1A1, and three human K+ channel genes--KCNA5, KCNA6, and KCNA1--map close to D12S99, but the Ca++ channel gene is unlikely to be the site of the defect, because crossovers have been observed to occur between the disease gene and a CA-repeat marker located close to this gene. Studies of a large EA family with a different clinical phenotype (MIM 108500), which lacks myokymia but is associated with nystagmus, have excluded the gene causing that disease from the chromosome 12p locus.
Interfused semiconductor nanocrystals: brilliant blue photoluminescence and electroluminescence (2005)

We describe a method for producing blue light-emitting interfused CdSe//ZnS (QE up to 60%) nanocrystals and report the good performance of an electroluminescent device which uses them (external quantum efficiency approximately 1.5 cd A(-1)).
Heterogeneous catalysis by solid superacids. 25. Antimony pentafluoride/graphite catalyzed oxidative carbonylation of methyl halides with carbon monoxide and copper oxides (or copper/oxygen) to methyl acetate (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHeterogeneous catalysis by solid superacids. 25. Antimony pentafluoride/graphite catalyzed oxidative carbonylation of methyl halides with carbon monoxide and copper oxides (or copper/oxygen) to methyl acetateGeorge A. Olah and Jozef BukalaCite this: J. Org. Chem. 1990, 55, 14, 4293–4297Publication Date (Print):July 1, 1990Publication History Published online1 May 2002Published inissue 1 July 1990https://pubs.acs.org/doi/10.1021/jo00301a017https://doi.org/10.1021/jo00301a017research-articleACS PublicationsRequest reuse permissionsArticle Views126Altmetric-Citations10LEARN 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
Crystal Structure of the Mycobacterium tuberculosis Enoyl-ACP Reductase, InhA, in Complex with NAD+ and a C16 Fatty Acyl Substrate (1999)

Enoyl-ACP reductases participate in fatty acid biosynthesis by utilizing NADH to reduce the trans double bond between positions C2 and C3 of a fatty acyl chain linked to the acyl carrier protein. The enoyl-ACP reductase from Mycobacterium tuberculosis, known as InhA, is a member of an unusual FAS-II system that prefers longer chain fatty acyl substrates for the purpose of synthesizing mycolic acids, a major component of mycobacterial cell walls. The crystal structure of InhA in complex with NAD+ and a C16 fatty acyl substrate, trans-2-hexadecenoyl-(N-acetylcysteamine)-thioester, reveals that the substrate binds in a general "U-shaped" conformation, with the trans double bond positioned directly adjacent to the nicotinamide ring of NAD+. The side chain of Tyr158 directly interacts with the thioester carbonyl oxygen of the C16 fatty acyl substrate and therefore could help stabilize the enolate intermediate, proposed to form during substrate catalysis. Hydrophobic residues, primarily from the substrate binding loop (residues 196-219), engulf the fatty acyl chain portion of the substrate. The substrate binding loop of InhA is longer than that of other enoyl-ACP reductases and creates a deeper substrate binding crevice, consistent with the ability of InhA to recognize longer chain fatty acyl substrates.
Reduced hepatitis B virus surface antigen-specific Th1 helper cell frequency of chronic HBV carriers is associated with a failure to produce antigen-specific antibodies in the Trimera mouse (2000)

In chronic hepatitis B virus (HBV) infection weak antiviral immune responses are associated with viral persistence. We studied possible immune deficits underlying the lack of serum antibodies of such patients against the HBV surface antigen (HBsAg) in a novel human/mouse chimeric model. A hepatitis B surface antigen (HBs) vaccination of Balb/c mice engrafted with peripheral blood mononuclear cells (PBMC) of naturally HBV-immunized donors induced high frequencies of human HBsAg-specific B and T helper 1 (Th1) cells. These responses were associated with high serum anti-HBs antibody levels of the subclasses immunoglobulin G1 (IgG1) and IgG2 that are driven by interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). In contrast, PBMC of chronic HBV carriers transplanted into the chimera failed to produce anti-HBs antibodies after vaccination with HBsAg and exhibited a deficit of antigen-specific Th1 cells. A possible influence of HBsAg or viremia was excluded by the lack of viral replication in such chimera. The observed T-cell defect was specific for HBsAg, as the B- and T-cell responses to tetanus toxoid (TT) were fully retained. Thus, our study shows that viral persistence in chronic HBV carriers is associated with an HBsAg-specific Th1 cell defect, which likely is responsible for the insufficient neutralizing anti-HBs-antibody response and is not reversed by HBs vaccination. Alternative approaches to induce HBs-specific Th1 cell responses might represent a future therapeutic option.
Clinical evolution of luminal and perianal Crohn's disease after inducing remission with infliximab: how long should patients be treated? (2005)

Short regimens of infliximab might be evaluated in patients with luminal Crohn's disease. However, infliximab discontinuation is not recommended in perianal Crohn's disease, because of a high rate of early relapse.