gebhart/patrepeval huggingface dataset:
Analysis of the Cellular Mechanism of Antitumor Responses and Autoimmunity in Patients Treated with CTLA-4 Blockade (2005)

We have demonstrated previously that the administration of CTLA-4 blockade has mediated objective cancer regression and autoimmunity in patients with metastatic melanoma. To explore the mechanism of these in vivo effects, we have studied the changes in lymphocyte phenotype and function in patients receiving anti-CTLA-4 Ab (MDX-010). Patients with stage IV melanoma or renal cell cancer were treated every 3 wk with an anti-CTLA-4 Ab with or without peptide immunization. Pheresis samples were analyzed using flow cytometry to determine lymphocyte cell surface markers. Gene expression analyses and proliferation assays were conducted on purified T cell subsets. Anti-CTLA-4 Ab did not inhibit the suppressive activity of CD4+CD25+ cells in vitro or in vivo. In addition, there was no decrease in the expression of CD4+CD25+ cells in whole PBMC, nor a decrease in Foxp3 gene expression in the CD4+ or CD4+CD25+ purified cell populations posttreatment. The percentage of CD4+, CD8+, CD4+CD25+, and CD4+CD25- T cells in PBMC expressing the activation marker HLA-DR increased following anti-CTLA-4 Ab administration. Therefore, our results suggest that the antitumor effects of CTLA-4 blockade are due to increased T cell activation rather than inhibition or depletion of T regulatory cells.
Oxidized high density lipoprotein induces macrophage apoptosis via toll-like receptor 4-dependent CHOP pathway (2016)

Oxidized HDL (ox-HDL), unlike native HDL that exerts antiatherogenic effects, plays a proatherogenic role. However, the underlying mechanisms are not completely understood. This study was designed to explore the inductive effect of ox-HDL on endoplasmic reticulum (ER) stress-CCAAT-enhancer-binding protein homologous protein (CHOP)-mediated macrophage apoptosis and its upstream mechanisms. Our results showed that ox-HDL could be ingested by macrophages, causing intracellular lipid accumulation. As with tunicamycin (an ER stress inducer), ox-HDL induced macrophage apoptosis with concomitant activation of ER stress pathway, including nuclear translocation of activating transcription factor 6, phosphorylation of protein kinase-like ER kinase and eukaryotic translation initiation factor 2α, and upregulation of glucose-regulated protein 78 and CHOP, which were inhibited by 4-phenylbutyric acid (PBA, an ER stress inhibitor) and CHOP gene silencing. Additionally, diphenyleneiodonium (DPI, an oxidative stress inhibitor), probucol (a reactive oxygen species scavenger), and toll-like receptor 4 (TLR4) silencing reduced ox-HDL-induced macrophage apoptosis, oxidative stress, and CHOP upregulation. Moreover, HDL isolated from patients with metabolic syndrome induced macrophage apoptosis, oxidative stress, and CHOP upregulation, which were blocked by PBA and DPI. These data indicate that ox-HDL may activate ER stress-CHOP-induced apoptotic pathway in macrophages via enhanced oxidative stress and that this pathway may be mediated by TLR4.
FTY720 Stimulates 27-Hydroxycholesterol Production and Confers Atheroprotective Effects in Human Primary Macrophages (2010)

We conclude that FTY720 decreases cholesterol toxicity in primary human macrophages by reducing the delivery of scavenged lipoprotein cholesterol to the endoplasmic reticulum and facilitating its release to physiological extracellular acceptors. Furthermore, FTY720 stimulates 27-hydroxycholesterol production, providing an explanation for the atheroprotective effects and identifying a novel mechanism by which FTY720 modulates signaling.
Exosome and Exosomal MicroRNA: Trafficking, Sorting, and Function (2015)

Exosomes are 40-100 nm nano-sized vesicles that are released from many cell types into the extracellular space. Such vesicles are widely distributed in various body fluids. Recently, mRNAs and microRNAs (miRNAs) have been identified in exosomes, which can be taken up by neighboring or distant cells and subsequently modulate recipient cells. This suggests an active sorting mechanism of exosomal miRNAs, since the miRNA profiles of exosomes may differ from those of the parent cells. Exosomal miRNAs play an important role in disease progression, and can stimulate angiogenesis and facilitate metastasis in cancers. In this review, we will introduce the origin and the trafficking of exosomes between cells, display current research on the sorting mechanism of exosomal miRNAs, and briefly describe how exosomes and their miRNAs function in recipient cells. Finally, we will discuss the potential applications of these miRNA-containing vesicles in clinical settings.
Optical response of Ag2, Ag3, Au2, and Au3 in argon matrices (1993)

We report on the optical response of size selected Ag2, Ag3, Au2, and Au3 embedded in argon matrices. Cluster samples were investigated in situ by excitation, fluorescence, and absorption spectroscopy. The spectra for the dimers are in agreement with previous measurements made on conventionally prepared matrices. Our previously reported spectra of trimers in krypton are confirmed by the argon results. The influence of the matrix gas will briefly be discussed.
Immunomagnetic CD4+ and CD8+ cell depletion for patients at high risk for severe acute GVHD. (1996)

Acute GVHD remains a major problem in allogeneic BMT, in particular when donors other than HLA-identical siblings are used. To determine the efficacy of an immunomagnetic method for depletion of CD4+ and CD8+ lymphocytes from the marrow graft, a series of 15 patients was studied. Thirteen patients had matched unrelated donors, and two patients had related donors. Cyclosporine was used as GVHD prophylaxis in combination with CD4+ and CD8+ depletion, which removed 94.1 +/- 3.2%, 97.0 +/- 5.1%, and 96.7 +/- 3.1% of CD3+, CD4+ and CD8+ cells, respectively. All patients engrafted promptly with AGC > 500/mm3 after a median of 16 days post-BMT. Acute GVHD grade II-IV developed in 0/2 related transplants and 4/13 MUD transplants; only one patient had grade III-IV acute GVHD. No late graft failure was observed. Three patients relapsed; two had advanced disease at the time of BMT. Seven patients are alive and in CCR after a median of 497 days; actuarial survival is 39% at 24 months. The fever syndrome observed with selective CD8+ cell depletion was not seen with the combined CD4+ and CD8+ cell depletion. Immunomagnetic CD4+ and CD8+ cell depletion of marrow grafts, in combination with in vivo cyclosporine, is a simple, reproducible and effective method to decrease the incidence and severity of acute GVHD in patients at high risk for this complication after allogeneic BMT.
Human carbonic anhydrase IV: cDNA cloning, sequence comparison, and expression in COS cell membranes. (1992)

We have isolated a full-length cDNA for human carbonic anhydrase IV (CA IV) from a lambda gt10 human kidney cDNA library. The 1105-base-pair (bp) cDNA contains a 47-bp 5' untranslated region, a 936-bp open reading frame, and a 122-bp 3' untranslated region. The deduced amino acid sequence is colinear with the N-terminal sequence and the sequence of several tryptic peptides of human lung CA IV. It includes an 18-amino acid signal sequence, a 260-amino acid region that shows 30-36% similarity with the 29-kDa cytoplasmic CAs (CA I, CA II, and CA III), and an additional 27-amino acid C-terminal sequence that ends in a 21-amino acid hydrophobic domain. Of the 17 "active site" residues that are highly conserved in other human CAs, 16 are also present in CA IV. Expression of the cDNA in COS cells produced a 35-kDa enzyme that was membrane associated, resistant to inactivation by SDS, contained no carbohydrate, and reacted on Western blots with antiserum to the 35-kDa CA IV from human lung. Treatment of membranes from transfected COS cells with phosphatidylinositol-specific phospholipase C released 20-30% of the expressed enzyme from membranes, indicating that at least 20-30% of the expressed enzyme was anchored to membranes by a glycosyl-phosphatidylinositol linkage.
Maintenance of bone mass and architecture in denning black bears (Ursus americanus) (2004)

Abstract Bone mass is dramatically compromised during periods of weightlessness, inactivity, or bed rest. Animals that hibernate reduce their body temperature, heart rate and metabolic activity, and likewise lower bone turnover activity during their immobile state. Black bears Ursus americanus , however, do not hibernate, but rather overwinter by denning during which they maintain a nearly normal functional heart rate, cardiac output and temperature. Furthermore, markers of bone turnover in black bears are maintained during denning periods. Thus, the purpose of this work was to determine if the denning state of relative immobility in black bears results in changes in bone mass and bone architectural structure. Harvested forelimbs (ulna and radius) were compared between pre‐ and post‐denning black bears using X‐ray imaging, dual energy X‐ray absorptiometry, and micro‐computed tomography to quantify total distal forelimb bone mineral density, cancellous bone mineral density, bone mineral content, bone volume fraction, degree of anisotropy, structure model index, and trabecular thickness. No significant differences in any of the measured parameters were found in comparing radius and ulna from autumn and spring bears in this cross‐sectional sample, suggesting that black bears did not experience a significant change in bone mass or architecture during denning. The statistical power for detecting a significant difference ( P ≤ 0.05) for this sample was 0.8. The specific mechanism by which the preservation of bone was attained may be related to skeletal muscle interaction or circulating systemic hormones.
Real-time optical eigenmode characterisation (2014)

An optical system is characterised by its transmission eigenmodes. Here, we are using a digital micromirror device to detect these optical eigenmodes experimentally and to achieve applications in aberration correction and imaging.
Frequency-domain reflectance for the determination of the scattering and absorption properties of tissue (1991)

Measurements of the phase and modulation of amplitudemodulated light diffusely reflected by turbid media can be used to deduce absorption and scattering coefficients.
Membrane Type 1 Matrix Metalloproteinase Expression in Human Atherosclerotic Plaques (1999)

This study demonstrates that MT1-MMP, an activator of pro-MMP-2, is expressed by SMCs and Mphi in human atherosclerotic plaques. Furthermore, proinflammatory molecules upregulate MT1-MMP expression in vascular SMCs and Mphi. Thus, activation of SMCs and Mphi by proinflammatory molecules may influence extracellular matrix remodeling in atherosclerosis by regulating MT1-MMP expression.
Topological mapping for mobile robots using a combination of sonar and vision sensing (1994)

Topological maps represent the world as a network of nodes and arcs: the nodes are distinctive places in the environment and the arcs represent paths between places. A significant issue in building topological maps is defining distinctive places. Most previous work in topological mapping has concentrated on using sonar sensors to define distinctive places. However, sonar sensors are limited in range and angular resolution, which can make it difficult to distinguish between different distinctive places. Our approach combines a sonar-based definition of distinctive places with visual information. We use the robot's sonar sensors to determine where to capture images and use cues extracted from those images to help perform place recognition. Information from these two sensing modalities is combined using a simple Bayesian network. Results described in this paper show that our robot is able to perform place recognition without having to move through a sequence of places, as is the case with most currently implemented systems.
N-Acetylglucosamine Functions in Cell Signaling (2012)

The amino sugar N-acetylglucosamine (GlcNAc) is well known for the important structural roles that it plays at the cell surface. It is a key component of bacterial cell wall peptidoglycan, fungal cell wall chitin, and the extracellular matrix of animal cells. Interestingly, recent studies have also identified new roles for GlcNAc in cell signaling. For example, GlcNAc stimulates the human fungal pathogen Candida albicans to undergo changes in morphogenesis and expression of virulence genes. Pathogenic E. coli respond to GlcNAc by altering the expression of fimbriae and CURLI fibers that promote biofilm formation and GlcNAc stimulates soil bacteria to undergo changes in morphogenesis and production of antibiotics. Studies with animal cells have revealed that GlcNAc influences cell signaling through the post-translational modification of proteins by glycosylation. O-linked attachment of GlcNAc to Ser and Thr residues regulates a variety of intracellular proteins, including transcription factors such as NFκB, c-myc and p53. In addition, the specificity of Notch family receptors for different ligands is altered by GlcNAc attachment to fucose residues in the extracellular domain. GlcNAc also impacts signal transduction by altering the degree of branching of N-linked glycans, which influences cell surface signaling proteins. These emerging roles of GlcNAc as an activator and mediator of cellular signaling in fungi, animals, and bacteria will be the focus of this review.
Detailed analysis of grid‐based molecular docking: A case study of CDOCKER—A CHARMm‐based MD docking algorithm (2003)

The influence of various factors on the accuracy of protein-ligand docking is examined. The factors investigated include the role of a grid representation of protein-ligand interactions, the initial ligand conformation and orientation, the sampling rate of the energy hyper-surface, and the final minimization. A representative docking method is used to study these factors, namely, CDOCKER, a molecular dynamics (MD) simulated-annealing-based algorithm. A major emphasis in these studies is to compare the relative performance and accuracy of various grid-based approximations to explicit all-atom force field calculations. In these docking studies, the protein is kept rigid while the ligands are treated as fully flexible and a final minimization step is used to refine the docked poses. A docking success rate of 74% is observed when an explicit all-atom representation of the protein (full force field) is used, while a lower accuracy of 66-76% is observed for grid-based methods. All docking experiments considered a 41-member protein-ligand validation set. A significant improvement in accuracy (76 vs. 66%) for the grid-based docking is achieved if the explicit all-atom force field is used in a final minimization step to refine the docking poses. Statistical analysis shows that even lower-accuracy grid-based energy representations can be effectively used when followed with full force field minimization. The results of these grid-based protocols are statistically indistinguishable from the detailed atomic dockings and provide up to a sixfold reduction in computation time. For the test case examined here, improving the docking accuracy did not necessarily enhance the ability to estimate binding affinities using the docked structures.
DNA sequencing of four bases using three lanes (1992)

A three-lane DNA sequencing strategy is described which is based on redundant binary coding principles from communications theory. Three-lane sequencing is an efficient, accurate, and flexible strategy, suitable for large-scale automated DNA sequencing. Communications theory and algebraic coding principles can also be applied to sequencing other informational macromolecules.
Comparison of vascular leak syndrome in mice treated with IL21 or IL2. (2013)

Interleukin 21 (IL21) is a T-cell-derived 4-helix-bundle cytokine that has sequence homology to the IL2 family. Recombinant human interleukin 2 (rIL2) is approved for the treatment of metastatic melanoma and renal cell carcinoma. However, toxicity of rIL2, including induction of vascular leak syndrome (VLS), has limited use of this cytokine to a small proportion of eligible patients. Both rIL2 and murine IL21 (mIL21) have potent antitumor efficacy in murine models. The purpose of the current study was to compare the ability of mIL21 and rIL2 to induce vascular leakage in a mouse model. Pulmonary and hepatic uptake of Evans blue dye, serum cytokine levels, spleen cell immunophenotype, and histologic changes in lung and liver were evaluated to detect VLS. High-dose (200 μg) rIL2 treatment induced vascular leakage in mice, evidenced by inflammatory cell infiltration and fluid extravasation into the lung and liver and increased levels of TNFα, IFNγ, IL5, MCP1, and IL6 in serum. In contrast, an equivalent dose of mIL21 resulted in minimal vascular leakage with no evidence of cytopenia or cytokine production. These results support the use of IL21 as a cancer immunotherapeutic agent, potentially providing an antitumor response without induction of VLS.
High power laser welding in hyperbaric gas and water environments (1997)

A hyperbaric laser welding facility has been constructed and the feasibility of high power CO2 and Nd:YAG laser welding in both high pressure gas and water environments, to simulated water depths of 500 m, has been established. From initial trials on welding through water at atmospheric pressure, it was found that the different absorption characteristics of water to 10.6 μm (CO2 laser) and 1.06 μm (Nd:YAG laser) radiation proved crucial. The Nd:YAG laser was totally unsuitable as the beam was largely diffused in the water, whereas the CO2 beam was readily absorbed and, using high speed video equipment, was found to form a high irradiance channel and a dry region around the weld area. Welding under a high pressure gas environment produced a highly energized plume which prevented keyhole welding at pressures over 1 × 106 Pa. An investigation carried out into the efficacy of a gas jet delivery system to alleviate the extent of the plume showed that argon blown horizontally across the weld was the optimum configuration, extending the welding range up to 5 × 106 Pa. A limited investigation into high pressure underwater welding showed porosity to be a problem although sound welds were produced at pressures up to 2 × 106 Pa.
FM-based indoor localization (2012)

The major challenge for accurate fingerprint-based indoor localization is the design of robust and discriminative wireless signatures. Even though WiFi RSSI signatures are widely available indoors, they vary significantly over time and are susceptible to human presence, multipath, and fading due to the high operating frequency. To overcome these limitations, we propose to use FM broadcast radio signals for robust indoor fingerprinting. Because of the lower frequency, FM signals are less susceptible to human presence, multipath and fading, they exhibit exceptional indoor penetration, and according to our experimental study they vary less over time when compared to WiFi signals. In this work, we demonstrate through a detailed experimental study in 3 different buildings across the US, that FM radio signal RSSI values can be used to achieve room-level indoor localization with similar or better accuracy to the one achieved by WiFi signals. Furthermore, we propose to use additional signal quality indicators at the physical layer (i.e., SNR, multipath etc.) to augment the wireless signature, and show that localization accuracy can be further improved by more than 5%. More importantly, we experimentally demonstrate that the localization errors of FM andWiFi signals are independent. When FM and WiFi signals are combined to generate wireless fingerprints, the localization accuracy increases as much as 83% (when accounting for wireless signal temporal variations) compared to when WiFi RSSI only is used as a signature.
Adipose Tissue-Derived Factors: Impact on Health and Disease (2006)

The endocrine functions of the adipose organ are widely studied at this stage. The adipose organ, and in particular adipocytes, communicate with almost all other organs. Although some adipose tissue pads assume the functions as distinct "miniorgans," adipocytes can also be present in smaller numbers interspersed with other cell types. Although fat pads have the potential to have a significant systemic impact, adipocytes may also affect neighboring tissues through paracrine interactions. These local or systemic effects are mediated through lipid and protein factors. The protein factors are commonly referred to as adipokines. Their expression and posttranslational modifications can undergo dramatic changes under different metabolic conditions. Due to the fact that none of the mutations that affect adipose tissue trigger embryonic lethality, the study of adipose tissue physiology lends itself to genetic analysis in mice. In fact, life in the complete absence of adipose tissue is possible in a laboratory setting, making even the most extreme adipose tissue phenotypes genetically amenable to be analyzed by disruption of specific genes or overexpression of others. Here, we briefly discuss some basic aspects of adipocyte physiology and the systemic impact of adipocyte-derived factors on energy homeostasis.
2M‐SASW: Multifold multichannel seismic inversion of local dispersion of Rayleigh waves in laterally heterogeneous subsurfaces: application to the Super‐Sauze earthflow, France (2006)

The approach presented here deals with the inversion of Rayleigh wave dispersion (SASW: Spectral Analysis of Surface Waves) in laterally heterogeneous media. The traditional method consists of computing the frequency versus phase‐velocity curve, known as the dispersion curve, from seismic records, then inverting to obtain a 1D shear‐wave velocity model. When media are laterally heterogeneous, S‐wave velocity changes lead to phase variations in Rayleigh waves in the offset dimension. This phenomenon can drastically alter the dispersion image, since it affects the local slopes of Rayleigh waves in the shot gather, and thus their phase‐velocity dispersion properties. In the case of multifold acquisitions (2M‐SASW: Multifold and Multichannel SASW), we redefine the manner in which the dispersion‐image calculation is formulated in order to compute the local dispersion stack (LDS). In principle, this consists of gathering receivers within a restricted window for a series of shots and computing the local dispersion images that are then stacked in order to improve the signal‐to‐noise ratio. Even though local dispersion diagrams are noisy because they are computed from a limited number of traces, the summation over multiple dispersion images enables the quality of the final LDS to be improved. Because it is related to the dispersion properties of the windowed wavefield, the LDS is an efficient input for the 1D inversion process. The method is tested on synthetic data to demonstrate its contribution compared to that of the traditional SASW technique. An application of the 2M‐SASW method to the Super‐Sauze earthflow confirms that is well‐suited to inverting the shear‐wave velocity from Rayleigh‐wave dispersion when high‐contrast media are considered.
Evidence for cyclic AMP-dependent protein kinase activity in isolated guinea pig and rat liver mitochondria. (1976)

Purified preparations of guinea pig and rat liver mitochondria contain considerable latent cAMP-dependent protein kinase activity that is revealed by treatment with 1% Triton X-100. The solubilized kinase was partly purified by DEAE-cellulose chromatography. It accepts protein in the washed Triton-extracted mitochondria as substrate.