gebhart/patrepeval huggingface dataset:
Sialic Acid Blockade Suppresses Tumor Growth by Enhancing T-cell–Mediated Tumor Immunity (2018)

Sialic acid sugars on the surface of cancer cells have emerged as potent immune modulators that contribute to the immunosuppressive microenvironment and tumor immune evasion. However, the mechanisms by which these sugars modulate antitumor immunity as well as therapeutic strategies directed against them are limited. Here we report that intratumoral injections with a sialic acid mimetic Ac<sub>5</sub>3F<sub>ax</sub>Neu5Ac block tumor sialic acid expression <i>in vivo</i> and suppress tumor growth in multiple tumor models. Sialic acid blockade had a major impact on the immune cell composition of the tumor, enhancing tumor-infiltrating natural killer cell and CD8<sup>+</sup> T-cell numbers while reducing regulatory T-cell and myeloid regulatory cell numbers. Sialic acid blockade enhanced cytotoxic CD8<sup>+</sup> T-cell-mediated killing of tumor cells in part by facilitating antigen-specific T-cell-tumor cell clustering. Sialic acid blockade also synergized with adoptive transfer of tumor-specific CD8<sup>+</sup> T cells <i>in vivo</i> and enhanced CpG immune adjuvant therapy by increasing dendritic cell activation and subsequent CD8<sup>+</sup> T-cell responses. Collectively, these data emphasize the crucial role of sialic acids in tumor immune evasion and provide proof of concept that sialic acid blockade creates an immune-permissive tumor microenvironment for CD8<sup>+</sup> T-cell-mediated tumor immunity, either as single treatment or in combination with other immune-based intervention strategies.<b>Significance:</b> Sialic acid sugars function as important modulators of the immunosuppressive tumor microenvironment that limit potent antitumor immunity.<b>Graphical Abstract:</b> http://cancerres.aacrjournals.org/content/canres/78/13/3574/F1.large.jpg <i>Cancer Res; 78(13); 3574-88. ©2018 AACR</i>.
An approach for the analysis of relapse and marrow reconstitution after autologous marrow transplantation using retrovirus-mediated gene transfer (1992)

Autologous bone marrow transplantation (ABMT) is widely used as treatment for malignant disease. Although the major cause of treatment failure is relapse, it is unknown if this arises entirely because of residual disease in the patient or whether contaminating cells in the rescuing marrow contribute. Attempts to purge marrow of its putative residual malignant cells may delay hematopoietic reconstitution and are of uncertain efficacy. We now describe how retrovirus-mediated gene transfer may be used to elucidate the source of relapse after ABMT for acute myeloid leukemia and to evaluate the efficacy of purging. Clonogenic myeloid leukemic blast cells in patient marrow can be transduced with the NeoR gene-containing helper-free retrovirus, LNL6, with an efficacy of 0% to 23.5% (mean, 10.5%). Transduced colonies grow in selective media and the presence of the marker gene can be confirmed in individual malignant colonies by polymerase chain reaction. If such malignant cells remain in harvested "remission" marrow, they will therefore be marked after exposure to LNL6. Detection of the marker gene in the malignant cells present at any later relapse would be firm evidence that residual disease contributed to disease recurrence, and would permit rapid subsequent evaluation of purging techniques. The technique also marks normal marrow progenitors from patients with acute myeloblastic leukemia. These colony-forming cells can be detected in long-term marrow cultures at a frequency of 1% to 18% for up to 10 weeks after exposure to the vector. Animal models and analysis of probability tables both suggest that these levels of marking in vitro are sufficient to provide information about the mechanisms of relapse and the biology of marrow regeneration in vivo. These preclinical data form part of the basis for current clinical studies of gene transfer into marrow before ABMT.
Evaluation of protein C and other biomarkers as predictors of mortality in a rat cecal ligation and puncture model of sepsis* (2004)

The data from this study indicate that an early decrease in protein C concentration predicts poor outcome in a rat sepsis model. The data further indicate that increases in the CXC chemokines macrophage inflammatory protein-2 and KC precede poor outcome.
Fluoxetine and Fluvoxamine Combined with Individual Cognitive-Behaviour Therapy in Binge Eating Disorder: A One-Year Follow-Up Study (2001)

CBT was more effective than FLX or FLV in the treatment of BED. The addition of FLX to CBT does not seem to provide any clear advantage, while the addition of FLV could enhance the effects of CBT on eating behaviours. Modifications of eating behaviours are maintained at the 1-year follow-up, although the lost weight was partly regained.
Lignin: Occurrence, Biogenesis and Biodegradation (1990)

Crop loss due to soil salinization is an increasing threat to agriculture worldwide. This review provides an overview of cellular and physiological mechanisms in plant responses to salt. We place cellular responses in a time- and tissue-dependent context ...Read More
<title>QBIC project: querying images by content, using color, texture, and shape</title> (1993)

In the query by image content (QBIC) project we are studying methods to query large on-line image databases using the images' content as the basis of the queries. Examples of the content we use include color, texture, and shape of image objects and regions. Potential applications include medical (`Give me other images that contain a tumor with a texture like this one'), photo-journalism (`Give me images that have blue at the top and red at the bottom'), and many others in art, fashion, cataloging, retailing, and industry. Key issues include derivation and computation of attributes of images and objects that provide useful query functionality, retrieval methods based on similarity as opposed to exact match, query by image example or user drawn image, the user interfaces, query refinement and navigation, high dimensional database indexing, and automatic and semi-automatic database population. We currently have a prototype system written in X/Motif and C running on an RS/6000 that allows a variety of queries, and a test database of over 1000 images and 1000 objects populated from commercially available photo clip art images. In this paper we present the main algorithms for color texture, shape and sketch query that we use, show example query results, and discuss future directions.
Noncontact, low‐frequency ultrasound as an effective therapy against Pseudomonas aeruginosa–infected biofilm wounds (2013)

Bacterial biofilms, a critical chronic wound mediator, remain difficult to treat. Energy-based devices may potentially improve healing, but with no evidence of efficacy against biofilms. This study evaluates noncontact, low-frequency ultrasound (NLFU) in the treatment of biofilm-infected wounds. Six-millimeter dermal punch wounds in rabbit ears were inoculated with 10(7) colony-forming units of Pseudomonas aeruginosa or left as sterile controls. A biofilm was established in vivo using our published model. NLFU treatment was carried out every other day or every day, with contralateral ear wounds acting as internal, untreated controls. Wounds were harvested for several quantitative endpoints and scanning electron microscopy to evaluate the biofilm structure. The P. aeruginosa biofilm consistently impaired wound epithelialization and granulation. NLFU, both every other day and every day, improved healing and reduced bacterial counts relative to untreated controls (p < 0.05). Scanning electron microscopy confirmed a qualitative decrease in bacteria after both treatments. NLFU also reduced inflammatory cytokine expression (p < 0.05). Our study suggests that NLFU is an effective therapy against P. aeruginosa wound biofilm. This represents the first in vivo evidence of energy-based modalities' impact on wound biofilm, setting the foundation for future mechanistic studies. Continued wound care technology research is essential to improving our understanding, and treatment, of biofilm-infected chronic wounds.
Phospholipase A2 activation in human neutrophils requires influx of extracellular Ca2+ and leukotriene B4 (1995)

We have demonstrated that phospolipase A2 (PLA2) activation in human neutrophils requires both the influx of extracellular Ca2+ and leukotriene B4 (LTB4). Surprisingly, the eicosanoids (LTB4 and its omega-oxidation products) formed were quantitatively very similar in both thapsigargin (Thap)- and A-23187-stimulated neutrophils. In contrast, Thap had very little effect on the activation of PLA2 when 5-lipoxygenase (5-LO) was blocked by BW755C or MK-886, whereas A-23187 caused a substantial activation. The lack of PLA2 activation in Thap-stimulated neutrophils results from the inhibition of LTB4 formation in the presence of 5-LO inhibitors. It appears that A-23187 activates both LTB4-dependent and -independent PLA2, whereas Thap activates LTB4-dependent PLA2. Experiments with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid demonstrated that activation of Thap-sensitive PLA2 and 5-LO requires the influx of Ca2+. Neither the transient elevation of cytosolic Ca2+ from intracellular stores nor the sustained Ca2+ influx alone without LTB4 appears sufficient to cause the activation of LTB4-dependent PLA2. We suggest that the activation of LTB4-dependent PLA2 involves 1) a sustained elevation of cytosolic Ca2+ coupled to the influx of extracellular Ca2+ and 2) a coupling between LTB4 and its receptor. We conclude that LTB4-dependent PLA2 plays an important role in the poststimulatory formation of lipid mediators such as prostaglandins, leukotrienes, and platelet-activating factor.
Effect of Deep Eutectic Solvent Nanostructure on Phospholipid Bilayer Phases (2017)

Phospholipids are shown by solvent penetration experiments to form lamellar phases and spontaneously spawn vesicles in a wide range of deep eutectic solvents (DESs) composed of alkylammonium halide salts and glycerol or ethylene glycol, which are shown to be nanostructured by X-ray scattering. In contrast with molecular solvents, the chain melting temperature of each phospholipid, which determines the stability of the swellable bilayer phase, depends on the structure of the cation, anion, and molecular H-bond donor that constitute the DES. Chain melting is most sensitive to the length of the alkyl chain of the cation, which is partitioned between apolar domains in the bulk, nanostructured DES and those within the lipid bilayer. This is moderated by the structures of the anion and the molecular hydrogen bond donor, which determine the extent of polar/apolar segregation in the bulk liquid.
Machine perfusion in organ transplantation (2012)

Machine perfusion of solid organs has regained much attention during the last decade. It provides a new promising tool that may allow pretransplant ex-vivo assessment, preservation, repair, and conditioning of grafts. Experimental research and clinical trials testing the administration of MSCs during machine perfusion are warranted to explore the potential benefit and mechanisms of this approach.
Suppression of the kink effect in InGaAs/InAlAs HEMTs grown by MBE by optimizing the InAlAs buffer layer (2003)

The authors have examined the effects of InP substrate preparation and InAlAs growth temperature on the structural, electrical. and optical properties of In/sub 0.52/Al/sub 0.48/As layers grown on InP substrate. The substrate cleanliness affects the InAlAs growth mode while the growth temperature determines the kinetics of growth. It is concluded that the optimum InAlAs buffer layers have to be grown at T/sub G/=530 degrees C and the InP substrate has to be cleaned at T/sub t/=530 degrees C in order to obtain low defect density, smooth interfaces, and high resistivity with minimum carrier trapping or compensation centers. This optimization of the InAlAs buffer layer is of critical importance for the kink effect and, consequently, for the output conductance of the HEMTs (high electron mobility transistors) on InP. The optimized HEMT structures exhibited high transconductance, 530 mS/mm for 1- mu m gate length, low output conductance (19 mS/mm), and almost elimination of the kink effect on the I-V characteristics.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Morphology definition by disclinations and dislocations in a mesostructured silicate crystal (1997)

Curved surface morphologies resulting from disclinations are unusual in inorganic phases because the relatively large lattice energies generally permit only translational dislocations. In this letter, we show, however, that disclinations can be readily observed and identified in composite organic/inorganic phases. Disclinations and dislocations in MCM-41, a two-dimensional hexagonal (p6mm) mesophase crystal synthesized using silicate and surfactant precursors, were investigated by using transmission electron microscopy. We observed two types of dislocations and two types of disclinations. All dislocations observed are of the smallest Burgers vector a (the basis vector). Dislocation dipoles and disclination quadrupoles appear more frequently than isolated ones.
Important immunoregulatory role of interleukin-11 in the inflammatory process in rheumatoid arthritis (1998)

IL-11 has important endogenous immunoregulatory effects in RA synovium, which suggests that exogenous IL-11 may have therapeutic activity in RA.
Dendritic cells that process and present nominal antigens to naive T lymphocytes are derived from CD2+ precursors (1997)

Dendritic cells (DC) are potent APC that, in mature form, can be distinguished from other mononuclear cells on the basis of their distinct morphology, absence of lineage markers, and dense expression of MHC and costimulatory molecules. While comparing different DC preparation methods, we observed that DC derived from cultured PBMC that had been depleted of CD2+ cells before culture were functionally distinct from DC derived from PBMC that had not been depleted of CD2+ cells. Thus, both types of DC stimulated allogeneic T cells to proliferate in the MLR, but only DC derived from CD2+ precursors could sensitize naive T cells to soluble Ags such as keyhole limpet hemocyanin and HIV gp160 glycoprotein. Subsequent studies confirmed the existence of CD2+ and CD2- DC precursor populations among HLA-DRbright, lineage-negative PBMC. Immediately after their isolation, these populations were morphologically similar to one another by light and electron microscopy, and neither had substantial Ag-presenting activity. After culture for 24 to 48 h with supernatant from PHA-activated PBMC, both populations developed dendrites, formed clusters with T cells, and stimulated allogeneic T cell responses in the MLR as well as autologous T cell responses to tetanus toxoid, a recall Ag. However, CD2+ DC precursors alone gave rise to APC that presented soluble Ags to naive CD4+ T cells, a property that could be inhibited by Abs to CD4, CD11a, and CD28 on T cells or CD86 on DC. The expression of CD54 and CD86 on CD2+ DC precursors was increased markedly after their culture and differentiation, while the expression of these molecules on CD2- DC precursors was not remarkably changed. These findings reveal the existence of two functionally distinct populations of DC, each derived from a phenotypically distinct precursor present in monocyte-depleted peripheral blood.
Computational Fluid Dynamics Simulations of Intracranial Aneurysms at Varying Heart Rates: A “Patient-Specific” Study (2009)

Rupture of an intracranial aneurysm (IA) is frequently associated with intense physical exertion and/or emotional excitement, events that are typically also accompanied by sudden significant changes in both heart rate and blood pressure. Very few experimental studies of aneurysm hemodynamics have examined the impact on hemodynamic parameters in and around an aneurysm resulting from changes in heart rate. In order to further understanding these changes, as they relate to hemodynamic features that may contribute to rupture of an IA, we examined the characteristics of pulsatile flow in and around two "patient-specific" intracranial aneurysms at three different cardiac frequencies. Three dimensional X-ray angiographic data (3D-DSA) were used to reconstruct accurate and patient-specific aneurysm geometries. Then, computational fluid dynamics techniques were utilized to analyze the characteristics of blood flow in and around the two aneurysms. Physiologically realistic flow conditions, as measured by transcranial Doppler ultrasound, were used in the simulations. Our results showed that there were significant changes in the overall flow patterns (e.g., vortex formation and translation) associated with the changes of heart rates. In both aneurysms, the calculated wall shear stress exhibited substantial increases with an increase in heart rate. Our results suggest that the changes in local hemodynamic forces associated with variations in heart rate are dependent not only on the heart rate but also on the aneurysm geometry. This thus precludes applying our observations about the impact of variations in cardiac rate to aneurysms in general.
A Drosophila CREB/ATF transcriptional activator binds to both fat body- and liver-specific regulatory elements. (1992)

We have identified a Drosophila transcription factor that binds to fat body-specific enhancers of alcohol dehydrogenase (Adh) and yolk protein genes. DNA sequence analysis of cDNA clones encoding this protein, box B-binding factor-2 (BBF-2), indicates that it is a member of the CREB/ATF family of transcriptional regulatory proteins. A number of observations suggest that BBF-2 is involved in fat body-specific expression: Mutations that disrupt BBF-2 binding to two different Adh fat body enhancers in vitro decrease the activity of these enhancers in transgenic flies. BBF-2 mRNA is present in all cell types examined, and the protein is present in cells that express ADH. Finally, BBF-2 is a transcriptional activator in Drosophila tissue culture cells. Remarkably, BBF-2 also binds specifically to regulatory elements required for liver-specific expression of the human Adh and rat tyrosine aminotransferase genes. Thus, BBF-2 and the DNA sequence to which it binds may be important components of a tissue-specific regulatory mechanism conserved between Drosophila and man.
Human CD4 helper T cell activation: functional involvement of two distinct collagen receptors, 1F7 and VLA integrin family. (1990)

In the present study, we showed that activation of human CD4 T cells can be induced by anti-CD3 and collagen in a serum-free system. This activation was inhibited by the addition of peptides containing the RGD or Gly-Pro-X sequences. Significantly, we demonstrated that both the 1F7 (CD26) structure and the VLA integrin family, particularly the VLA-3 complex, contribute to the functional interaction between collagen and CD4 cells since anti-1F7 and anti-VLA-3 specifically inhibited this collagen-induced CD4 cell activation. Biochemical studies showed that the 1F7 structure is not a member of the VLA integrin family. These results thus indicated that two different families of antigens serve as functional collagen receptors for CD4 T cell activation.
The Adenovirus Inverted Terminal Repeat Functions as an Enhancer in a Cell-free System (1989)

Two binding sites for EivF, a factor involved in transcription from the adenovirus early promoter iv (Eiv), were mapped within the adenovirus inverted terminal repeats (ITR). Consistent with the observation that EivF was required to initiate transcription from the Eiv promoter and with the demonstration that two EivF binding sites were present in the ITR, we show that the inverted terminal repeat region was able to promote transcription from the CAP site of the Eiv promoter in vitro and in an EIa-dependent fashion in vivo. The minimum sequence within the ITR capable of directing EIa-dependent transcription consists of forty nine nucleotides comprising two EivF binding sites and at least one Sp1 binding site. This 49-base pair fragment possesses the characteristics of an enhancer which is induced by EIa. The enhancer is active in HeLa cell nuclear extracts. Transcription directed by the ITR required EivF and the general transcription factors. The addition of purified Sp1 factor specifically stimulated transcription which correlates with the presence of Sp1 binding sites between the two EivF recognition sites.
Density evolution for two improved BP-Based decoding algorithms of LDPC codes (2002)

In this letter, we analyze the performance of two improved belief propagation (BP) based decoding algorithms for LDPC codes, namely the normalized BP-based and the offset BP-based algorithms, by means of density evolution. The numerical calculations show that with one properly chosen parameter for each of these two improved BP-based algorithms, performances very close to that of the BP algorithm can be achieved. Simulation results for LDPC codes with code length moderately long validate the proposed optimization.
Coordinated changes in AHRR methylation in lymphoblasts and pulmonary macrophages from smokers (2012)

Smoking is associated with a wide variety of adverse health outcomes including cancer, chronic obstructive pulmonary disease, diabetes, depression, and heart disease. Unfortunately, the molecular mechanisms through which these effects are conveyed are not clearly understood. To examine the potential role of epigenetic factors in these processes, we examined the relationship of smoking to genome wide methylation and gene expression using biomaterial from two independent samples, lymphoblast DNA and RNA (n = 119) and lung alveolar macrophage DNA (n = 19). We found that in both samples current smoking status was associated with significant changes in DNA methylation, in particular at the aryl hydrocarbon receptor repressor (AHRR), a known tumor suppressor. Both baseline DNA methylation and smoker associated DNA methylation signatures at AHRR were highly correlated (r = 0.94 and 0.45, respectively). DNA methylation at the most differentially methylated AHRR CpG residue in both samples, cg0557592, was significantly associated with AHRR gene expression. Pathway analysis of lymphoblast data (genes with most significant methylation changes) demonstrated enrichment in protein kinase C pathways and in TGF beta signaling pathways. For alveolar macrophages, pathway analysis demonstrated alterations in inflammation-related processes. We conclude that smoking is associated with functionally significant genome wide changes in DNA methylation in both lymphoblasts and pulmonary macrophages and that further integrated investigations of these epigenetic effects of smoking on carcinogenesis and other related co-morbidities are indicated.
Double-strand breaks at the target locus stimulate gene targeting in embryonic stem cells (1995)

Double-strand breaks (DSBs) are recombinogenic lesions in chromosomal DNA in yeast, Drosophila and Caenorhabditis elegans. Recent studies in mammalian cells utilizing the I-Scel endonuclease have demonstrated that in some immortalized cell lines DSBs in chromosomal DNA are also recombinogenic. We have now tested embryonic stem (ES) cells, a non-transformed mouse cell line frequently used in gene targeting studies. We find that a DSB introduced by I-Scel stimulates gene targeting at a selectable neo locus at least 50-fold. The enhanced level of targeting is achieved by transient expression of the I-Scel endonuclease. In 97% of targeted clones a single base pair polymorphism in the transfected homologous fragment was incorporated into the target locus. Analysis of the targeted locus demonstrated that most of the homologous recombination events were 'two-sided', in contrast to previous studies in 3T3 cells in which 'one-sided' homologous events predominated. Thus ES cells may be more faithful in incorporating homologous fragments into their genome than other cells in culture.