gebhart/patrepeval huggingface dataset:
PA28 and the proteasome immunosubunits play a central and independent role in the production of MHC class I‐binding peptides in vivo (2011)

Proteasomes play a fundamental role in the processing of intracellular antigens into peptides that bind to MHC class I molecules for the presentation of CD8(+) T cells. Three IFN-γ-inducible catalytic proteasome (immuno)subunits as well as the IFN-γ-inducible proteasome activator PA28 dramatically accelerate the generation of a subset of MHC class I-presented antigenic peptides. To determine whether these IFN-γ-inducible proteasome components play a compounded role in antigen processing, we generated mice lacking both PA28 and immunosubunits β5i/LMP7 and β2i/MECL-1. Analyses of MHC class I cell-surface levels ex vivo demonstrated that PA28 deficiency reduced the production of MHC class I-binding peptides both in cells with and without immunosubunits, in the latter cells further decreasing an already diminished production of MHC ligands in the absence of immunoproteasomes. In contrast, the immunosubunits but not PA28 appeared to be of critical importance for the induction of CD8(+) T-cell responses to multiple dominant Influenza and Listeria-derived epitopes. Taken together, our data demonstrate that PA28 and the proteasome immunosubunits use fundamentally different mechanisms to enhance the supply of MHC class I-binding peptides; however, only the immunosubunit-imposed effects on proteolytic epitope processing appear to have substantial influence on the specificity of pathogen-specific CD8(+) T-cell responses.
NETosis: how vital is it? (2013)

In this review, we examine the evidence that neutrophil extracellular traps (NETs) play a critical role in innate immunity. We summarize how NETs are formed in response to various stimuli and provide evidence that NETosis is not universally a cell death pathway. Here we describe at least 2 different mechanisms by which NETs are formed, including a suicide lytic NETosis and a live cell or vital NETosis. We also evaluate the evidence for NETs in catching and killing pathogens. Finally, we examine how infections are related to the development of autoimmune and vasculitic diseases through unintended but detrimental bystander damage resulting from NET release.
Neonatal Candidiasis Among Extremely Low Birth Weight Infants: Risk Factors, Mortality Rates, and Neurodevelopmental Outcomes at 18 to 22 Months (2006)

Blood cultures were negative for approximately one half of the infants with Candida meningitis. Persistent candidiasis was common. Delayed catheter removal was associated with increased death and NDI rates.
A Lecithin Cholesterol Acyltransferase-like Gene Mediates Diacylglycerol Esterification in Yeast (2000)

The terminal step in triglyceride biosynthesis is the esterification of diacylglycerol. To study this reaction in the model eukaryote, Saccharomyces cerevisiae, we investigated five candidate genes with sequence conservation to mammalian acyltransferases. Four of these genes are similar to the recently identified acyl-CoA diacylglycerol acyltransferase and, when deleted, resulted in little or no decrease in triglyceride synthesis as measured by incorporation of radiolabeled oleate or glycerol. By contrast, deletion of LRO1, a homolog of human lecithin cholesterol acyltransferase, resulted in a dramatic reduction in triglyceride synthesis, whereas overexpression of LRO1 yielded a significant increase in triglyceride production. In vitro microsomal assays determined that Lro1 mediated the esterification of diacylglycerol using phosphatidylcholine as the acyl donor. The residual triglyceride biosynthesis that persists in the LRO1 deletion strain is mainly acyl-CoA-dependent and mediated by a gene that is structurally distinct from the previously identified mammalian diacylglycerol acyltransferase. These mechanisms may also exist in mammalian cells.
Nonhistaminergic and mechanical itch sensitization in atopic dermatitis (2017)

Chronic or episodic severe itch is recurrent in atopic dermatitis (AD). Nonhistaminergic itch pathways are suggested to dominate in AD itch, contributing to an "itch-scratch-itch cycle" that prolongs and worsens itch, pain, and skin lesions. We hypothesized that nonhistaminergic neuronal sensitization contributes to itch in AD. Hence, we compared sensitivity with thermal, mechanical, and chemical pruritic stimuli in patients with AD and controls. The study comprised 25 patients with AD with chronic itch and 25 healthy controls. Questionnaires on itch characteristics were administered, and sensory tests were conducted intralesionally, extralesionally, and in homologous areas of controls. Thermal and mechanical quantitative sensory testing (QST) as well as histamine and cowhage provocations were performed. Subsequently, hyperknesis and vasomotor reactivity were assessed. Average itch and associated pain among patients with AD were 60.7 ± 4.3 and 39.7 ± 5.2 (VAS0-100), respectively. Patients experienced significantly higher itch from cowhage both intralesionally and extralesionally compared with controls, whereas histamine-evoked itch intensity was not significantly different between groups. No group differences were found for thermal quantitative sensory testings or pain evoked by itch provocations. Patients had decreased mechanical detection thresholds intralesionally and increased mechanical pain sensitivity intralesionally and extralesionally. Lastly, patients exhibited intralesional and extralesional hyperknesis before chemical itch provocations and augmented hyperknesis after itch provocations. Increased itch in response to cowhage (but not histamine) suggests nonhistaminergic pathway-specific itch sensitization in AD, whereas increased susceptibility to mechanically evoked itch and pain, particularly intralesionally suggests sensitization of mechanosensitive circuitry not normally associated with itch. Drugs targeting the nonhistaminergic (PAR2/TRPA1) itch pathway and itch sensitization are promising for treating AD itch.
ETS2 Mediated Tumor Suppressive Function and MET Oncogene Inhibition in Human Non–Small Cell Lung Cancer (2013)

Our findings point to a tumor suppressor role for ETS2 in human NSCLC pathogenesis through inhibition of the MET proto-oncogene.
New approaches to the prevention and treatment of severe S. aureusinfections (2000)

Staphylococcus aureus is a virulent pathogen that is currently a major cause of community-acquired infections, as well as infections in hospitalized patients. Morbidity and mortality due to S. aureus infections, such as sepsis, osteomyelitis, septic arthritis and infective endocarditis, remain high despite the use of newer antibiotics. Of major concern, methicillin resistance in S. aureus isolates has increased dramatically worldwide, especially among nosocomial isolates; this phenotype may be associated with resistance to other antistaphylococcal compounds, including vancomycin. This increase in prevalence of multiantibiotic resistance in S. aureus is a major public health concern. Currently, there is an intense focus on the development of novel vaccines for the prevention of S. aureus infections in high-risk populations and on new antimicrobial classes for the therapy of established S. aureus infections.
Extracellular annexin II is associated with divalent cation‐dependent tumor cell–endothelial cell adhesion of metastatic RAW117 large‐cell lymphoma cells (1993)

Using fixed microvessel endothelial cell monolayers the molecules involved in the adhesion of liver-preferring murine RAW117 large cell lymphoma cells to murine liver-derived microvessel endothelial cells were identified by affinity isolation. Detergent lysates obtained from poorly (P) or highly (H10) liver-metastatic cells inhibited RAW117-H10 cell adhesion to hepatic sinusoidal endothelial (HSE) cell monolayers. Allowing detergent lysates of cell surface-labeled RAW117 cells to bind to fixed HSE cell monolayers and eluting the bound components indicated that several tumor cell surface molecules (approximately 70, approximately 35, approximately 32, approximately 22, and approximately 14 kDa) might be involved in RAW117 cell-HSE cell adhesion. The approximately 35 kDa component was cation dependent in its binding to target HSE cells. Increasing detergent concentration had no effect on binding of the approximately 35 kDa component to HSE cell monolayers, whereas treatment with 0.5 M NaCl resulted in its selective elution from HSE cells. Incubation of the HSE cell monolayers with detergent lysates from cell surface-labeled RAW117-H10 cells resulted in selective depletion of the approximately 35 kDa component, suggesting that the binding is saturable. This divalent cation-dependent molecule is one of the major tumor cell surface components bound by several types of endothelial cells and murine hepatocytes, whereas there was poor binding of this component to unfixed or fixed human red blood cells. The purified, partially (approximately 40%) sequenced molecule had amino acid sequence identity with murine but not bovine annexin II, indicating that it was not bound from the bovine serum used to grow RAW117 cells. Using antibodies specific for annexin II flow cytometry indicated equivalent amounts of annexin II are expressed on RAW117 cell surfaces in the absence or presence of excess EDTA, whereas annexin I was only found in low amounts on the surfaces of RAW117 cells. Annexin II antibodies inhibited by approximately 40-50% the adhesion of RAW117 tumor cells to live or fixed endothelial cells, and purified tumor cell surface fractions containing the approximately 35 kDa component partially inhibited (approximately 35%) RAW117 cell-HSE cell adhesion. The data indicate that annexin II is expressed on the extracellular surface of RAW117 cells, and cell surface-annexin II mediates a portion of the Ca(2+)-dependent RAW117 cell adhesion to liver microvessel endothelial cells.
Mechanism of YadA-mediated serum resistance of Yersinia enterocolitica serotype O3 (1992)

Complement activation via the alternative pathway was analyzed with isogenic strains of Yersinia enterocolitica serotype O3 differing in plasmid content (p- or p+ strains) or selective lack of YadA expression (YadA- strain). The p+ strain was serum resistant, even after antibody-enhanced complement activation. Serum sensitivity was observed with the p- and YadA- strains but was more pronounced in the p- strain. The p+ strain deposited less C5b-9(m) complexes on its surface than the p- and YadA- strains. No size difference, however, was detected with solubilized C5b-9(m) complexes obtained from resistant and sensitive strains. At the C3 level, it became evident that surface-bound C3b was degraded faster into iC3b on the p+ strain than on the p- and YadA- strains. Our results demonstrate that YadA inhibits complement activation at the C3 and C9 level. As a result, reduced amounts of C5b-9(m) are generated on the surface of YadA-bearing bacteria. In addition, YadA seems to protect against the lytic action of those C5b-9(m) complexes whose deposition could not be prevented.
Effect of magnetic fields on tumor growth and viability. (2011)

Breast cancer is the most common nonskin cancer and is the second leading cause of cancer-related deaths in women. Most methods of intervention involve combinations of surgery, chemotherapy, and ionizing radiation. Both chemotherapy and ionizing radiation can be effective against many types of cancer, but they also harm normal tissues. The use of nonionizing, magnetic fields has shown early promise in a number of in vitro and animal studies. Our study tested the effect of varying durations of magnetic exposure on tumor growth and viability in mice injected with breast cancer cells. Cancer cells were labeled through stable expression of firefly luciferase for monitoring of tumor growth and progression by using an in vivo imaging system. We hypothesized that magnetic field exposure would influence tumor growth and progression. Our results showed that exposure of the mice to magnetic fields for 360 min daily for as long as 4 wk suppressed tumor growth. Our study is unique in that it uses an in vivo imaging system to monitor the growth and progression of tumors in real time in individual mice. Our findings support further exploration of the potential of magnetic fields in cancer therapeutics, either as adjunct or primary therapy.
Cyclic AMP (2008)

Cyclic adenosine monophosphate (cAMP) was the original "second messenger" to be discovered. Its formation is promoted by adenylyl cyclase activation after ligation of G protein-coupled receptors by ligands including hormones, autocoids, prostaglandins, and pharmacologic agents. Increases in intracellular cAMP generally suppress innate immune functions, including inflammatory mediator generation and the phagocytosis and killing of microbes. The importance of the host cAMP axis in regulating antimicrobial defense is underscored by the fact that microbes have evolved virulence-enhancing strategies that exploit it. Many clinical situations that predispose to infection are associated with increases in cAMP, and therapeutic strategies to interrupt cAMP generation or actions have immunostimulatory potential. This article reviews the anatomy of the cAMP axis, the mechanisms by which it controls phagocyte immune function, microbial strategies to dysregulate it, and its clinical relevance.
Modulation of T-cell responses to alloantigens by TR6/DcR3 (2001)

TR6 (DcR3) is a new member of the TNF receptor (TNFR) family that lacks a transmembrane domain in its sequence, indicating that it is a secreted molecule. TR6 can bind to FasL and prevent FasL-induced apoptosis; it can also associate with LIGHT, another TNF family member. The role of TR6 in immune responses was investigated in this study. According to flow cytometry, recombinant human TR6-Fc binds to human LIGHT expressed on 293 cells or on activated human T cells and competes with the LIGHT receptor TR2 for the binding to LIGHT on these cells. Human TR6 could cross-react with mouse LIGHT in immunoprecipitation. TR6-Fc also downregulates cytotoxic T lymphocyte activity in vitro and graft-versus-host responses in mice. Moreover, TR6-Fc modulates lymphokine production by alloantigen-stimulated mouse T cells. TR6-Fc ameliorated rejection response to mouse heart allograft. These results indicate that TR6 can dampen T-cell responses to alloantigens. Such regulatory effects of TR6 probably occur via interference with interaction between pairs of related TNF and TNFR family members, LIGHT/TR2 being one of the possible candidate pairs.
Spatial-Depth Super Resolution for Range Images (2007)

We present a new post-processing step to enhance the resolution of range images. Using one or two registered and potentially high-resolution color images as reference, we iteratively refine the input low-resolution range image, in terms of both its spatial resolution and depth precision. Evaluation using the Middlebury benchmark shows across-the-board improvement for sub-pixel accuracy. We also demonstrated its effectiveness for spatial resolution enhancement up to 100 times with a single reference image.
Re‐expression of C/EBPα induces CYP2B6, CYP2C9 and CYP2D6 genes in HepG2 cells (1998)

Cytochrome P450 (CYP) activity is very low or even absent in human hepatomas, a phenomenon that is accompanied by low levels of some liver transcription factors, notably C/EBP alpha. To investigate a possible link between this transcription factor and hepatic CYP expression, we have stably transfected HepG2 cells with a C/EBP alpha vector containing a Zn-inducible metallothionein promoter. Expression of functional C/EBP alpha up to liver levels concomitantly increased the mRNAs of several members of the CYP2 family (2B6, 2C9 and 2D6), suggesting that this transcription factor may play a relevant role in controlling the hepatic expression of CYP enzymes.
The Detection of Psilocin in Human Urine (2001)

Pharmacokinetic studies of psilocybin in humans have shown the rapid dephosphorylation of psilocybin to psilocin with further conversion to 4-hydroxy-tryptophole (4HT) and 4-hydroxyindole-3-acetic acid (4HIAA) in plasma. Our study shows that psilocin also undergoes conjugation and can be found in the urine as the psilocin-glucuronide conjugate. Recoveries after enzymatic hydrolysis of the urine with beta-glucuronidase (Helix Pomatia or E. Coli) when compared to non-hydrolyzed urine confirmed the presence of the glucuronide. Detection of psilocin from hydrolyzed and extracted samples was optimized for GC/MS by derivatization with MSTFA. The method developed allows for the detection of psilocin in urine with a limit of quantitation of 10 ng/mL, based on 5 mL of spiked urine. Using this method, our laboratory has confirmed the presence of psilocin in 6 out of 8 urine samples, with concentrations ranging from 10 ng/mL to greater than 200 ng/mL. Before implementation of the hydrolysis and derivatization steps, our limit of detection was 200 ng/mL, based on spiked urine standards. No case samples were positive without hydrolysis and derivatization.
Plasma and Skin Carriers for Natural and Synthetic Retinoids (1987)

Human skin contains several proteins that could bind the hydrophobic retinoids. One is retinol-binding protein (RBP), the plasma carrier of natural vitamin A, retinol, albumin, and two specific cellular-binding proteins, one for retinol (CRBP) and one for retinoic acid (CRABP). Adequate techniques for the study of these proteins in human skin have been developed; this was considered a necessary step in the understanding of how natural and synthetic retinoids work in the skin. A polyacrylamide gel electrophoresis technique followed by protein immunoblot analysis with an antiserum specific against RBP was developed. This technique allowed study of the binding of several natural and synthetic retinoids on the plasma carrier of natural vitamin A for the first time; it was found that only natural retinoids, including retinoic acid, bind to RBP in vitro; retinoic acid binding was found to induce major conformational changes in the protein. Isotretinoin did not bind to RBP. The technique was then used for the study of RBP in human epidermal and dermal extracts; it showed that RBP degradation with loss of binding properties for retinol occurred within the epidermis; this suggests that retinol supply is decreased within the epidermis, a fact that could be linked to cornification. A polyacrylamide gel electrophoresis binding assay was developed for studying CRBPs and CRABPs in human skin cytosolic extracts. This assay is more specific and more convenient than previous ones for studying tissue extracts. The CRABP was (1) in much higher levels in normal epidermis than in normal dermis, (2) dramatically elevated in psoriatic plaques and in some retinoid-responsive dermatoses, and (3) up modulated by both topical and systemic administration of natural and synthetic retinoids. Such alterations were not observed for CRBP. From these and other observations reviewed herein, it seems that CRABP should be one of the first candidates to be carefully analyzed in the search of the cellular receptor for the mediation of the synthetic retinoids in pharmacologic effects in human skin.
Quantitative relationships of intravascular tumor cells, tumor vessels, and pulmonary metastases following tumor implantation. (1974)

Summary An experimental model has been developed to quantify some of the major processes initiated by tumor transplantation and culminating in pulmonary metastases. The T241 fibrosarcoma, chosen because of its high hematogenous metastatic propensity and reproducible biological behavior, is transplanted into the femoral region of the C57BL mouse. Experiments are performed at specified times after transplantation to determine the dynamics of tumor growth, density, and size distribution of perfused tumor vessels, entry rate of tumor cells into the circulation, and the number of pulmonary metastases. Estimates of the entry rate of tumor cells into the circulation are obtained by perfusing tumors with an oxygenated, cell-free medium to allow the counting of single tumor cells and tumor cell clumps collected in the venous effluent. The tumor vascular network appears at approximately Day 4, while tumor cells are first observed in the perfusate approximately 5 days after transplantation. The concentration of effluent tumor cells, singly and in clumps, increases rapidly until Day 10, after which the rate of cell entry into the perfusion is diminished. A linear relation is found between the density of perfused vessels and the concentration of effluent tumor cells. Metastases, first observed on Day 10, increase rapidly with time, at a rate similar to that of the concentration of effluent tumor cell clumps containing 4 or more cells. These studies suggest that dynamics of hematogenously initiated metastases depend strongly on the entry rate of tumor cell clumps into the circulation, which in turn is intimately linked to tumor vascularization.
Phagocytic chimeric receptors require both transmembrane and cytoplasmic domains from the mannose receptor. (1992)

Phagocytosis has traditionally been viewed as a specialized function of myeloid and monocytic cells. The mannose receptor (MR) is an opsonin-independent phagocytic receptor expressed on tissue macrophages. When human MR cDNA is transfected into Cos cells, these usually non-phagocytic cells express cell surface MR and bind and ingest MR ligands such as zymosan, yeast, and Pneumocystis carinii. Expression of cDNA for Fc gamma RI (CD64), the high-affinity Fc receptor, in Cos cells confers binding but barely detectable phagocytosis of antibody-opsonized erythrocytes (EA). We report here that chimeric receptors containing the ligand-binding ectodomain of the Fc receptor and the transmembrane and cytoplasmic domains of the MR ingest bound EA very efficiently, whereas chimeras with the Fc receptor ecto- and transmembrane domains and the MR tail, or the Fc receptor ecto- and cytoplasmic domains and the MR transmembrane region, are significantly less phagocytic. All of the chimeric receptors bind ligand with equal avidity, but gain of functional phagocytosis is only conferred by the MR transmembrane and cytoplasmic domains. Endocytosis of monomeric immunoglobulin G by chimeric receptors demonstrates a similar pattern, with optimal uptake by the chimera containing both tail and transmembrane regions from the MR. The chimeric receptors with only the transmembrane or the cytoplasmic domain contributed by the MR were less efficient. Site-directed mutagenesis of the single tyrosine residue in the cytoplasmic tail (which is present in a motif homologous to an endocytosis consensus motif in the LDL receptor cytoplasmic tail [Chen, W.-J., J. L. Goldstein, and M. S. Brown. 1990. J. Biol. Chem. 265:3116]) reduces the efficiency of phagocytosis and endocytosis to a similar extent.
Universal linear optics (2015)

Linear optics underpins fundamental tests of quantum mechanics and quantum technologies. We demonstrate a single reprogrammable optical circuit that is sufficient to implement all possible linear optical protocols up to the size of that circuit. Our six-mode universal system consists of a cascade of 15 Mach-Zehnder interferometers with 30 thermo-optic phase shifters integrated into a single photonic chip that is electrically and optically interfaced for arbitrary setting of all phase shifters, input of up to six photons, and their measurement with a 12-single-photon detector system. We programmed this system to implement heralded quantum logic and entangling gates, boson sampling with verification tests, and six-dimensional complex Hadamards. We implemented 100 Haar random unitaries with an average fidelity of 0.999 ± 0.001. Our system can be rapidly reprogrammed to implement these and any other linear optical protocol, pointing the way to applications across fundamental science and quantum technologies.