gebhart/patrepeval huggingface dataset:
Sequence changes at the V-D junction of the VH1 heavy chain of anti- phosphocholine antibodies alter binding to and protection against Streptococcus pneumoniae (1997)

X-linked immune deficient (Xid) mice fail to produce anti-phosphocholine (PC) antibodies even after immunization with Streptococcus pneumoniae. Consequently, Xid mice are extremely susceptible to infection with S. pneumoniae, PC-specific B cells appear to undergo clonal deletion in Xid mice; however, a new thymus-dependent form of PC, 6-(O-phosphocholine)hydroxyhexanoate (EPC), can rescue PC-specific B cells from the bone marrow presumably by providing T cell help before clonal deletion. Analysis of PC-specific IgG hybridomas from Xid mice revealed utilization of several V-D junctional variants of the VH1 gene segment rearranged to different D and JH gene segments. The majority of Xid anti-PC antibodies exhibit an Asp-->Gly95H replacement at the V-D junction. These Gly95H VH1 variants associate with kappa 1C L chains to produce anti-PC antibodies that: (1) have low relative affinity for PC, (ii) are heteroclitic for nitrophenylphosphocholine and (iii) fall to bind to or provide protection against S. pneumoniae. Single prototypic V-D variants of the T15 idiotype (Asp95H), M603 idiotype (Asn95H) and M167 idiotype (Asp95H-Ala96H) were also induced in Xid mice. The M603-like and M167-like antibodies bound to and protected against S. pneumoniae even though they exhibited Kas for PC which were lower than T15 idiotype+ antibodies. These data demonstrate that small changes in the V-D junctional sequence of the T15 (VH1) heavy chain alter L chain usage and the structure of the PC binding site so that the PC expressed on S. pneumoniae is no longer recognized.
Transcriptional activation of the inducible nuclear receptor gene nur77 by nerve growth factor and membrane depolarization in PC12 cells. (1993)

nur77 is an immediate-early gene inducible by nerve growth factor or membrane depolarization in the rat pheochromocytoma cell line PC12 and by serum growth factors in fibroblasts. The nur77-encoded protein is a member of the steroid/thyroid hormone receptor superfamily and can act as a potent transcription activator. The induction of nur77 in PC12 cells is rapid and transient, with kinetics similar to those of the c-fos protooncogene. Induction does not require de novo protein synthesis. Whereas transcriptional activation of c-fos by nerve growth factor in PC12 cells requires a 20-base pair serum response element in its promoter, there is no such sequence in the nur77 promoter. To understand the mechanism for the activation of nur77, we have analyzed the inducibility of a series of transfected nur77 minigenes using an S1 nuclease protection assay. We identified the sequence 22-86 nucleotides upstream of the transcription start site as necessary and sufficient for nur77 induction by nerve growth factor and membrane depolarization in PC12 cells. Sequences farther upstream enhance the induction. Analysis of base substitution mutations allowed us to identify three sequence elements within this region that are essential for induction. These sequence elements include two copies of an AP1-like element and a GC-rich sequence. Unlike transcriptional activation of c-fos, the sequence requirements for the activation of nur77 by nerve growth factor and membrane depolarization cannot be readily separated. Taken together, our data suggest that activation of nur77 and c-fos by nerve growth factor occurs through different mechanisms in PC12 cells.
Cytotoxic and biochemical effects of thymidine and 3-deazauridine on human tumor cells. (1984)

Cytotoxicity and perturbations of the deoxyribonucleoside triphosphate pools caused by thymidine were studied in thymidine-sensitive and -resistant human tumor cells. Incubation with 1 mM thymidine reduced cell viability by more than 90% in the three sensitive cell lines (two melanomas and one adrenal carcinoma) and reduced the growth rate without decreasing the viability of resistant LO melanoma cells. Thymidine (1 mM) greatly increased the ratio of the deoxythymidine 5'-triphosphate to deoxycytidine 5'-triphosphate pools in the sensitive cells compared to LO cells and also caused larger relative increases in the pool sizes of deoxyguanosine 5'-triphosphate and deoxyadenosine 5'-triphosphate in the sensitive compared to the resistant cells. 3-Deazauridine, known to inhibit synthesis of deoxycytidine 5'-triphosphate and cytidine 5'-triphosphate in other cell lines, potentiated the cytotoxicity of thymidine for thymidine-sensitive BE melanoma and LO cells. In LO cells, 3-deazauridine (50 microM) decreased the intracellular pool of deoxycytidine 5'-triphosphate to the level obtained with 1 mM thymidine. Lower concentrations of deoxycytidine as compared to cytidine were required to protect BE and LO cells against the cytotoxicity of thymidine plus 3-deazauridine. Deoxycytidine also was more effective than was cytidine in preventing loss of cell viability after exposure to thymidine or to 3-deazauridine individually. In these human melanoma cells, ribonucleotide reductase may be a major site of action of thymidine, of 3-deazauridine, and of both drugs in combination. These results indicate that in human tumor cells the cytotoxic effect of thymidine correlates with greater perturbations of the pyrimidine deoxyribonucleoside 5'-triphosphate pools and that thymidine and 3-deazauridine, which independently reduce the intracellular levels of deoxycytidine 5'-triphosphate, act synergistically against human tumor cells.
Chiroptical methods in the stereochemical analysis of natural products (1975 to 1999) (2000)

The first page of this article is displayed as the abstract.
Long-term automated peritoneal dialysis in patients with refractory congestive heart failure. (2003)

Patients with severe congestive heart failure (CHF), mainly class IV on the New York Heart Association (NYHA) scale, became refractory to standard medical therapy. The factor that favored that evolution was renal insufficiency with inadequate renal perfusion. Our objectives in the present study were to make a preliminary assessment of the usefulness of automated peritoneal dialysis (APD) for the treatment of volume overload in those patients. Our study was carried out in the peritoneal dialysis unit of the clinical hospital of Pontificia Universidad Católica de Chile. We studied 3 non uremic patients with refractory CHF secondary to ischemic cardiomyopathy, severe secondary lung hypertension (> 70 mmHg), and associated moderate renal insufficiency. The patients (2 women and 1 man) ranged in age from 55 years to 68 years. A Tenckhoff double-cuff peritoneal catheter was placed in each patient, and peritoneal dialysis was carried out using the nightly intermittent peritoneal dialysis (NIPD) modality. The treatment used was appropriate to obtain a gradual removal of fluids: dialysate dextrose at 1.5% and 2.5%, 4-5 cycles, and total volume of 10-12 L per night. All three patients were able to remain at home, with no signs of hypervolemia. The frequency and length of hospitalizations decreased on average from 59 days pre-APD to 37 days post-APD. No hospitalizations for cardiac problems occurred, and the mean survival was 11 months (range: 6-22 months). This preliminary observation suggests that APD could be offered as an effective treatment for helping to remove fluids in patients with refractory CHF, reducing the number and length of hospitalizations, and improving quality of life.
Biochemical, Biophysical, and Pharmacological Characterization of Bacterially Expressed Human Agouti-Related Protein (1998)

The agouti-related protein gene (Agrp) is a novel gene implicated in the control of feeding behavior. The hypothalamic expression of Agrp is regulated by leptin, and overexpression of Agrp in transgenic animals results in obesity and diabetes. By analogy with the known actions of agouti, these data suggest a role for the Agrp gene product in the regulation of melanocortin receptors expressed in the central nervous system. The availability of recombinant, highly purified protein is required to fully address this potential interaction. A nearly full-length form of AGRP (MKd5-AGRP) was expressed in the cytosolic or soluble fraction of Escherichia coli and appeared as large intermolecular disulfide-bonded aggregates. Following oxidation, refolding, and purification, this protein was soluble, and eluted as a single symmetric peak on RP-HPLC. Circular dichroism studies indicated that the purified protein contains primarily random coil and beta-sheet secondary structure. Sedimentation velocity studies at neutral pH demonstrated that MKd5-AGRP is monomeric at low micromolar concentrations. Mobility shifts observed using SDS-PAGE under reducing and nonreducing conditions for bacterially expressed and mammalian expressed AGRP were identical, an indication of a similar disulfide structure. The purification to homogeneity of a second, truncated form of AGRP (Md65-AGRP) which was expressed in the insoluble or inclusion body fraction is also described. Both forms act as competitive antagonists of alpha-melanocyte stimulating hormone (alpha-MSH) at melanocortin-3 (MC-3) and melanocortin-4 receptors (MC-4). The demonstration that AGRP is an endogenous antagonist with respect to these receptors is a unique mechanism within the central nervous system, and has important implications in the control of feeding.
Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases define the migratory characteristics of human monocyte‐derived dendritic cells (2002)

Dendritic cells (DCs) have an essential role in the initiation of immune responses as they deliver antigen/epitope and the appropriate signals to activate naïve T cells and thus start an immune response. In order to fulfil their function, DCs have to patrol different part of the body, thus migrating through the extracellular matrix to sample the local 'antigenic' environment. In the present study, we have investigated which enzymes might be involved in this process using the Matrigel trans-well migration assay, an in vitro model of extracellular matrix migration. In this assay we analysed the migratory ability of interleukin-4 (IL-4)/granulocyte macrophage-colony-stimulating factor (GM-CSF)-derived immature DCs as well as mature DCs, induced by tumour necrosis factor-alpha (TNF-alpha) and modified vaccinia virus Ankara (MVA). The 'mature' DCs showed an increased migration through Matrigel, which was significantly inhibited by inhibitors of matrix metalloproteinases (MMP). We also observed that the dominant MMP involved in this process was MMP-9, and a concomitant decrease of the endogenous tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 was also observed. Collectively these data suggest that the balance between MMP/TIMP determines the net migratory capacity of human DCs. Surprisingly, TIMP-3 was significantly increased in mature DC. Our data thus indicate that MMP and TIMP play a role in the migratory ability of human DCs. Our results also suggest that TIMP-3 expression might represent a new marker of maturation of human DCs.
Exploitation of the xylem stream by parasitic organisms (1993)

Abstract A taxonomically diverse group of angiosperms and certain homopteran insects derive water, inorganic and organic solutes from angiosperm xylem sap. Parasitic angiosperms are connected to their host(s) by a specialized organ (the haustorium) and form close cellular contacts with host xylem tissue, while insects tap xylem vessels by means of stylets. Adaptations to phytophagy are discussed with respect to gaining access to xylem tissue and the nutrition of sap feeders. Parasitic angiosperm-host interactions are examined in relation to recent advances in our understanding of root-to-shoot communication via the xylem (the influence of host-sourced signals on the parasite) and the functional significance of high rates of transpiration in parasitic angiosperms.
CO2-Mediated ortho-Lithiation of N-Alkylanilines and Its Use for the Construction of Polymerization Catalysts (2008)

The ortho-lithiation of N-alkylanilines is accomplished by the treatment of tBuLi with the lithium carbamate compounds generated in situ from N-alkylanilines. The lithiated compounds attack the carbonyl-carbon on 2,3,4,5-tetramethylcyclopentenone, 1-indanone, or 9-fluorenone to yield tertiary alcohols, which are transformed to N-alkylanilines attaching a Me4C5, indenyl, or fluorenyl unit at an ortho-position. From the compounds, various o-phenylene-bridged (Me4C5, indenyl, or fluorenyl)/amido titanium complexes are prepared in one step. The Me4C5/ethylamido titanium complex exhibits a similar catalytic performance to the CGC [Me2Si(η5-Me4C5)(NtBu)]TiCl2 in ethylene/1-octene copolymerization in terms of activity, molecular weight of the obtained polymer, and 1-octene incorporation.
Raf pathway inhibitors in oncology. (2003)

Recognition of the importance of the Raf pathway in the proliferation and survival of tumor cells recently increased with the discovery of activating BRAF mutations in human tumors. Therefore, in addition to a role in controlling tumors with Ras mutations and activated growth factor receptors, inhibitors of the Raf pathway may harbor therapeutic potential in tumors carrying a BRAF oncogene. A variety of agents have been discovered that interfere with the Raf pathway, including antisense oligonucleotides and small molecules. These inhibitors block the expression of Raf protein, block Ras/Raf interaction, block its kinase activity, or block the kinase activity of the Raf target protein mitogen-activated protein kinase kinase. Raf pathway inhibitors that are currently undergoing clinical evaluation show promising signs of anticancer efficacy with a very tolerable safety profile. Indeed, the Raf inhibitor BAY-43-9006 recently entered phase III clinical trials. Here, we review the current development status of potential Raf pathway therapeutics.
Measurement of tumor markers in chronic hemodialysis patients. (2010)

Tumor markers are widely used for screening certain tumors, however, their use in chronic hemodialysis (HD) patients in hemodialysis has been a controversial issue. To determine the reliability of the tumor markers, CA 15-3, CA 19-9, CA 125, alpha-fetoprotein and carcinoembryonic antigen (CEA), in chronic HD patients, and the impact of active hepatitis C on the variation of tumor markers values, we studied 30 patients (16 men and 14 women) aged from 40 to 78 years old (mean age: 54 + or - 5 years), on intermittent hemodialysis (with a mean duration of 10.5 years), and clinically free from neoplastic disease. The control group included 30 healthy volunteers. All subjects were of Greek origin and residents of the Korinthos region. The tumor markers were measured once in the control group and before and afterwards the hemodialysis, in the study group. Alpha fetoprotein was within normal limits in all the study patients, CA 125 was slightly increased in one (3.3%) patient, CA 15-3 levels were twice normal in 4 (13%) patients, CA 19-9 levels were twice normal in 5 (16%) patients, and CEA levels were twice normal in 4(13%) patients. More than half (7/13) of anti HCV positive and all Australian antigen positive patients had abnormal serum levels of CA 15-3 and CA 125 after hemodialysis treatment. We conclude that measurement of some tumor markers such as alfa-fetoprotein may be beneficial in HD patients. However, the elevated levels of other markers including CA 15-3 and CA 125 are not specific for neoplasms and related to active hepatitis C.
The role of alpha-interferon in patients with human immunodeficiency virus infection. (1991)

alpha-Interferon (IFN alpha) blocks replication of human immunodeficiency virus (HIV)-1 in vitro by interfering with the release of mature virions. Clinical trials have addressed the in vivo effects of IFN alpha, both alone and in combination with other agents, in a variety of patients at all stages of HIV-1 infection. Patients with late stages of HIV-1 infection (CD4 counts under 100) show few positive results following treatment with IFN alpha. Patients with earlier stages of HIV infection, however, may benefit from treatment with this agent. Several clinical trials have demonstrated the activity of interferon in the treatment of patients with acquired immunodeficiency syndrome, Kaposi's sarcoma, and CD4 counts over 200. In these trials, response rates of approximately 40% have been reported, with the probability of response directly correlated with the level of CD4 cells. These antitumor effects have been associated with declines in the circulating levels of the HIV-1 core antigen p24. alpha-Interferon activity has also been studied in patients concomitantly receiving zidovudine. In these studies, neutropenia, reversible with the concomitant administration of granulocyte macrophage colony-stimulating factor, has been the most common dose-limiting toxicity. Both the antitumor and antiviral activities of combination therapy appear to be at least as good as those observed when single agents are used. Controlled clinical trials are currently under way to evaluate the role of interferon therapy, both alone and in combination with zidovudine, in patients with early HIV infection.
Robust Gaussian Process Regression for Real-Time High Precision GPS Signal Enhancement (2019)

Satellite-based positioning system such as GPS often suffers from large amount of noise that degrades the positioning accuracy dramatically especially in real-time applications. In this work, we consider a data-mining approach to enhance the GPS signal. We build a large-scale high precision GPS receiver grid system to collect real-time GPS signals for training. The Gaussian Process (GP) regression is chosen to model the vertical Total Electron Content (vTEC) distribution of the ionosphere of the Earth. Our experiments show that the noise in the real-time GPS signals often exceeds the breakdown point of the conventional robust regression methods resulting in sub-optimal system performance. We propose a three-step approach to address this challenge. In the first step we perform a set of signal validity tests to separate the signals into clean and dirty groups. In the second step, we train an initial model on the clean signals and then reweigting the dirty signals based on the residual error. A final model is retrained on both the clean signals and the reweighted dirty signals. In the theoretical analysis, we prove that the proposed three-step approach is able to tolerate much higher noise level than the vanilla robust regression methods if two reweighting rules are followed. We validate the superiority of the proposed method in our real-time high precision positioning system against several popular state-of-the-art robust regression methods. Our method achieves centimeter positioning accuracy in the benchmark region with probability $78.4\%$ , outperforming the second best baseline method by a margin of $8.3\%$. The benchmark takes 6 hours on 20,000 CPU cores or 14 years on a single CPU.
Homozygous autosomal dominant hypercholesterolaemia in the Netherlands: prevalence, genotype–phenotype relationship, and clinical outcome (2014)

The prevalence of molecularly defined hoADH is much higher and the clinical phenotype is more variable than previously assumed. In light of the fact that novel therapies are, or will be registered for the treatment of hoADH patients, an uniform definition of hoADH either as a phenotypic or molecular entity is warranted in order to identify patients who are considered to be eligible for these novel agents.
Freezing and thawing alter chromatin stability of ejaculated human spermatozoa: Fluorescence acridine orange staining and Feulgen‐DNA cytophotometric studies (1988)

Cryopreservation and freezing-thawing effects on the fertilizing ability of human spermatozoa commonly are evaluated by post-thaw motility. Various studies have depicted the ultrastructural changes caused by freezing-thawing, yet the chromatin alterations have been studied very limitedly. Our aim was to determine the extent to which freezing-thawing alters the chromatin of human spermatozoa, using two analytical methods: acridine orange staining and Feulgen-DNA cytophotometric studies. Both methods revealed a dramatic effect of freezing-thawing on sperm chromatin: the native DNA content decreased as did the Feulgen-DNA content, and sperm surface area was reduced. These results indicate an effect on DNA, diminished accessibility for Feulgen, and a decrease in nuclear surface area and prompt us to hypothesize a relationship between an "overcondensation" state for sperm chromatin after freezing-thawing and a lower conception rate for human semen after cryostorage.
Detection of ANA,anti-ENA antibodies and anti-dsDNA antibodies in lupus erythematosus (2002)

Objective:To discuss clinical value and characteristic of antinuclear antibody,anti-ENA antibodies and anti-dsDNA antibodies in lupus erythematosus.Methods:Indirect immunofluorescence was applied to detect ANA and anti-dsDNA antibodies. Antigenic substrate of ANA were liver imprint and Hep-2 cell. Test matrix of dsDNA was crithidia lucilliae flagellate. Detection of anti-ENA antibodies employed edenzyme immunoblotting assays.Results:The positive rate of ANA was 90.4% in SLE and 75% in DLE. The positive rate of anti-dsDNA antibodies was 63.5%,ENA was 84.5%.Conclusion:ANA has nothing to do with activity of SLE. Fluctuations in anti-dsDNA antibody levels are also used as a marker for disease activity and exacerbations.
Signaling of High Mobility Group Box 1 (HMGB1) through Toll-like Receptor 4 in Macrophages Requires CD14 (2013)

High mobility group box 1 (HMGB1) is a DNA-binding protein that possesses cytokinelike, proinflammatory properties when released extracellularly in the C23-C45 disulfide form. HMGB1 also plays a key role as a mediator of acute and chronic inflammation in models of sterile injury. Although HMGB1 interacts with multiple pattern recognition receptors (PRRs), many of its effects in injury models occur through an interaction with toll-like receptor 4 (TLR4). HMGB1 interacts directly with the TLR4/myeloid differentiation protein 2 (MD2) complex, although the nature of this interaction remains unclear. We demonstrate that optimal HMGB1-dependent TLR4 activation in vitro requires the coreceptor CD14. TLR4 and MD2 are recruited into CD14-containing lipid rafts of RAW264.7 macrophages after stimulation with HMGB1, and TLR4 interacts closely with the lipid raft protein GM1. Furthermore, we show that HMGB1 stimulates tumor necrosis factor (TNF)-α release in WT but not in TLR4(-/-), CD14(-/-), TIR domain-containing adapter-inducing interferon-β (TRIF)(-/-) or myeloid differentiation primary response protein 88 (MyD88)(-/-) macrophages. HMGB1 induces the release of monocyte chemotactic protein 1 (MCP-1), interferon gamma-induced protein 10 (IP-10) and macrophage inflammatory protein 1α (MIP-1α) in a TLR4- and CD14-dependent manner. Thus, efficient recognition of HMGB1 by the TLR4/MD2 complex requires CD14.
A genetic polymorphism in a functional domain of human pregnancy zone protein: the bait region (1990)

Genomic clones containing the exons coding for the bait domain of human pregnancy zone protein and alpha 2 macroglobulin were isolated and fragments containing the bait exons were sequenced. It is shown that the bait domains of both alpha 2 macroglobulin and pregnancy zone protein are encoded by two exons, with conserved exon/intron boundaries. A genetic polymorphism showing either a Met or a Val residue as the sixth amino acid of the pregnancy zone protein bait domain was detected with the rare Met allele showing a gene frequency of 0.065.