gebhart/patrepeval huggingface dataset:
Mouse Mammary Tumors Express Elevated Levels of RNA Encoding the Murine Homolog of SKY, a Putative Receptor Tyrosine Kinase (1995)

To gain insight into the signal transduction pathways utilized by the Wnt-1-responsive mammary epithelial cell line C57MG, we screened for non-src family member tyrosine kinases expressed in these cells using a polymerase chain reaction-based technique. We identified five cDNA clones encoding receptor tyrosine kinases for which the ligand is known (fibroblast growth factor receptor, platelet-derived growth factor receptor, epithelial growth factor receptor, insulin receptor, and insulin-like growth factor receptor), two putative receptor tyrosine kinases for which the ligand remains to be identified (the products of ryk and the mouse klg homolog), and a novel tyrosine kinase. We cloned cDNAs encoding both the murine and human homologs of this kinase, the sequences of which were subsequently published under the names sky (Ohashi, K., Mizuno, K., Kuma, K., Miyata, T., and Nakamura, T. (1994) Oncogene 9, 699-705) and rse (Mark, M. R., Scadden, D. T., Wang, Z., Gu, Q., Goddard, A., and Godowski, P. J. (1994) J. Biol. Chem. 269, 10720-10728). Mouse sky RNA levels are abundant in mammary tumors derived from transgenic mice that express wnt-1, fgf-3, or both oncogenes in their mammary glands. However, little or no expression of sky is detected in mammary glands from virgin animals or in preneoplastic mammary glands from wnt-1 transgenic mice. Moreover, we find that the human homolog of sky is expressed at elevated levels when normal human mammary epithelial cells are rendered tumorigenic by the introduction of two viral oncogenes. Transient transfection of the human SKY cDNA into the quail fibrosarcoma cell line QT6 reveals that SKY is an active tyrosine kinase that augments the level of cellular phosphotyrosine. Introduction of murine Sky into RatB1a fibroblasts by retrovirus-mediated gene transfer results in morphological transformation, growth in soft agar, and the formation of tumors in nude mice. These data raise the possibility that the Sky tyrosine kinase is involved in the development and/or progression of mammary tumors.
Cyclical Thrombocytopenia: Characterization by Spectral Analysis and a Review (1999)

We have analyzed published platelet time series in four normal individuals and 29 putative cyclical thrombocytopenia patients for evidence of significant ( p ≤ 0.05) cyclicity. Three of the normal individuals (all males) showed significant cycling (periods T of 23, 30 and 31 days) as did 15 of the cyclical thrombocytopenia patients (T from 13 to 65 days). Cyclical thrombocytopenia seems to be approximately equally prevalent in women and men, though in cases where a definite etiology was suggested an autoimmune origin occurs more frequently in women. We also briefly review the current state of knowledge of the control of platelet production by thrombopoietin (c‐Mpl ligand) and previous attempts that have been made to construct mathematical models for the platelet control system.
Estrogen-induced activation of mitogen-activated protein kinase requires mobilization of intracellular calcium (1999)

Estrogens and growth factors such as epidermal growth factor (EGF) act as mitogens promoting cellular proliferation in the breast and in the reproductive tract. Although it was considered originally that these agents manifested their mitogenic actions through separate pathways, there is a growing body of evidence suggesting that the EGF and estrogen-mediated signaling pathways are intertwined. Indeed, it has been demonstrated recently that 17beta-estradiol (E2) can induce a rapid activation of mitogen-activated protein kinase (MAPK) in mammalian cells, an event that is independent of both transcription and protein synthesis. In this study, we have used a pharmacological approach to dissect this novel pathway in MCF-7 breast cancer cells and have determined that in the presence of endogenous estrogen receptor, activation of MAPK by E2 is preceded by a rapid increase in cytosolic calcium. The involvement of intracellular calcium in this process was supported by the finding that the presence of EGTA and Ca2+-free medium did not affect the activation of MAPK by E2 and, additionally, that this response was blocked by the addition of the intracellular calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate. Cumulatively, these data indicate that the estrogen receptor, in addition to functioning as a transcription factor, is also involved, through a nongenomic mechanism, in the regulation of both intracellular calcium homeostasis and MAPK-signaling pathways. Although nongenomic actions of estrogens have been suggested by numerous studies in the past, the ability to link estradiol and the estrogen receptor to a well defined signaling pathway strongly supports a physiological role for this activity.
The Vitronectin Receptor and its Associated CD47 Molecule Mediates Proinflammatory Cytokine Synthesis in Human Monocytes by Interaction with Soluble CD23 (1999)

The vitronectin receptor, alphavbeta3 integrin, plays an important role in tumor cell invasion, angiogenesis, and phagocytosis of apoptotic cells. CD47, a member of the multispan transmembrane receptor family, physically and functionally associates with vitronectin receptor (VnR). Although vitronectin (Vn) is not a ligand of CD47, anti-CD47 and beta3 mAbs suppress Vn, but not fibronectin (Fn) binding and function. Here, we show that anti-CD47, anti-beta3 mAb and Vn, but not Fn, inhibit sCD23-mediated proinflammatory function (TNF-alpha, IL-12, and IFN-gamma release). Surprisingly, anti-CD47 and beta3 mAbs do not block sCD23 binding to alphav+beta3+ T cell lines, whereas Vn and an alphav mAb (clone AMF7) do inhibit sCD23 binding, suggesting the VnR complex may be a functional receptor for sCD23. sCD23 directly binds alphav+beta3+/CD47(-) cell lines, but coexpression of CD47 increases binding. Moreover, sCD23 binds purified alphav protein and a single human alphav chain CHO transfectant. We conclude that the VnR and its associated CD47 molecule may function as a novel receptor for sCD23 to mediate its proinflammatory activity and, as such, may be involved in the inflammatory process of the immune response.
Peroxiredoxin 1 Interacts with Androgen Receptor and Enhances Its Transactivation (2007)

Although hypoxia is accepted as an important microenvironmental factor influencing tumor progression and treatment response, it is usually regarded as a static global phenomenon. Consequently, less attention is given to the impact of dynamic changes in tumor oxygenation in regulating the behavior of cancer cells. Androgen receptor (AR) signaling plays a critical role in prostate cancer. We previously reported that hypoxia/reoxygenation, an in vitro condition used to mimic an unstable oxygenation climate in a tumor, stimulates AR activation. In the present study, we showed that peroxiredoxin 1 (Prx1), a member of the peroxiredoxin protein family, acts as a key mediator in this process. We found that the aggressive LN3, C4-2, and C4-2B prostate cancer cell lines derived from LNCaP possess constitutively elevated Prx1 compared with parental cells, and display greater AR activation in response to hypoxia/reoxygenation. Although the cell survival-enhancing property of Prx1 has traditionally been attributed to its antioxidant activity, the reactive oxygen species-scavenging activity of Prx1 was not essential for AR stimulation because Prx1 itself was oxidized and inactivated by hypoxia/reoxygenation. Increased AR transactivation was observed when wild-type Prx1 or mutant Prx1 (C52S) lacking antioxidant activity was introduced into LNCaP cells. Reciprocal immunoprecipitation, chromatin immunoprecipitation, and in vitro pull-down assays corroborated that Prx1 interacts with AR and enhances its transactivation. We also show that Prx1 is capable of sensitizing a ligand-stimulated AR. Based on the above information, we suggest that disrupting the interaction between Prx1 and AR may serve as a fruitful new target in the management of prostate cancer.
Localization of the hemochromatosis gene close to D6S105. (1993)

The hemochromatosis (HC) gene is known to be linked to HLA-A (6p21.3); however, its precise location has been difficult to determine because of a lack of additional highly polymorphic markers for this region. The recent identification of short tandem repeat sequences (microsatellites) has now provided this area with a number of markers with similar polymorphic index to the HLA serological polymorphisms. Using four microsatellites--D6S105, D6S109, D6S89, and F13A--together with the HLA class I loci HLA-A and HLA-B in 13 large pedigrees clearly segregating for HC, we have been able to refine the location of the HC gene. We identified no recombination between HC and HLA-A or D6S105, and two-point analyses placed the HC gene within one centimorgan (cM) of HLA-A and D6S105 (HLA-A maximum of the lod score [Zmax] of 9.90 at recombination fraction [theta] of 0.0, and D6S105 Zmax of 8.26 at theta of 0.0). The markers HLA-B, D6S109, D6S89, and F13A were separated from the HC locus by recombination, defining the centromeric and telomeric limits for the HC gene as HLA-B and D6S109, respectively. A multipoint map constructed using HLA-B, HLA-A, and D6S109 indicates that the HC gene is located in a region less than 1 cM proximal to HLA-A and less than 1 cM telomeric of HLA-A. These pedigree data indicate an association between HC and specific alleles at HLA-A and D6S105 (i.e., HLA-A3 and D6S105 allele 8).(ABSTRACT TRUNCATED AT 250 WORDS)
Alien Invaders! Post-visit Lesson (Grade 6) (2008)

The following post-visit activity is designed to synthesize and expand the knowledge students have gained in their Forever Earth experience by creating a Public Service Announcement (PSA) about an invasive species. By completing this activity, students re-analyze the impact of such species on an ecosystem and consider the value in educating and motivating the public in regard to invasive species.
Glucosamine protects neonatal cardiomyocytes from ischemia-reperfusion injury via increased protein-associated O-GlcNAc (2006)

Increased levels of protein O-linked N-acetylglucosamine (O-GlcNAc) have been shown to increase cell survival following stress. Therefore, the goal of this study was to determine whether in isolated neonatal rat ventricular myocytes (NRVMs) an increase in protein O-GlcNAcylation resulted in improved survival and viability following ischemia-reperfusion (I/R). NRVMs were exposed to 4 h of ischemia and 16 h of reperfusion, and cell viability, necrosis, apoptosis, and O-GlcNAc levels were assessed. Treatment of cells with glucosamine, hyperglycemia, or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)-amino-N-phenylcarbamate(PUGNAc), an inhibitor of O-GlcNAcase, significantly increased O-GlcNAc levels and improved cell viability, as well as reducing both necrosis and apoptosis compared with untreated cells following I/R. Alloxan, an inhibitor of O-GlcNAc transferase, markedly reduced O-GlcNAc levels and exacerbated I/R injury. The improved survival with hyperglycemia was attenuated by azaserine, which inhibits glucose metabolism via the hexosamine biosynthesis pathway. Reperfusion in the absence of glucose reduced O-GlcNAc levels on reperfusion compared with normal glucose conditions and decreased cell viability. O-GlcNAc levels significantly correlated with cell viability during reperfusion. The effects of glucosamine and PUGNAc on cellular viability were associated with reduced calcineurin activation as measured by translocation of nuclear factor of activated T cells, suggesting that increased O-GlcNAc levels may attenuate I/R induced increase in cytosolic Ca(2+). These data support the concept that activation of metabolic pathways leading to an increase in O-GlcNAc levels is an endogenous stress-activated response and that augmentation of this response improves cell survival. Thus strategies designed to activate these pathways may represent novel interventions for inducing cardioprotection.
Optical reflectometry based on correlation detection and its application to the in-service monitoring of WDM passive optical network (2007)

We propose and demonstrate a novel technique for measuring the distribution of the reflectivity along an optical fiber transmission line. Unlike the conventional optical time-domain reflectometer (OTDR), the proposed technique utilizes the data-modulated transmitter itself instead of the optical short-pulse source, and monitors the distribution of the back-reflected light by calculating the cross-correlation of the transmitted and back-reflected signals. In this paper, we describe the operating principle of the proposed technique and discuss its potential limitation on the dynamic range. We also show that this limitation can be mitigated by using the discrete-component elimination algorithm. In addition, we experimentally demonstrate that the proposed technique can be used for the in-service monitoring of the transmission fibers in a wavelength-division multiplexed passive optical network (WDM PON).
Magnesium Intake in Relation to Systemic Inflammation, Insulin Resistance, and the Incidence of Diabetes (2010)

Magnesium intake was inversely longitudinally associated with incidence of diabetes in young American adults. This inverse association may be explained, at least in part, by the inverse correlations of magnesium intake with systemic inflammation and insulin resistance.
New ionization methods and miniature mass spectrometers for biomedicine: DESI imaging for cancer diagnostics and paper spray ionization for therapeutic drug monitoring (2010)

The state-of-the-art in two new ambient ionization methods for mass spectrometry, desorption electrospray ionization (DESI) and paper spray (PS), is described and their utility is illustrated with new studies on tissue imaging and biofluid analysis. DESI is an ambient ionization method that can be performed on untreated histological sections of biological tissue in the open lab environment to image lipids, fatty acids, hormones and other compounds. Paper spray is performed in the open lab too; it involves electrospraying dry blood spots or biofluid deposits from a porous medium. PS is characterized by extreme simplicity and speed: a spot of whole blood or other biofluid is analyzed directly from paper, simply by applying a high voltage to the moist paper. Both methods are being developed for use in diagnostics as a means to inform therapy. DESI imaging is applied to create molecular maps of tissue sections without prior labeling or other sample preparation. Like other methods of mass spectrometry imaging (MSI), it combines the chemical speciation of multiple analytes with information on spatial distributions. DESI imaging provides valuable information which correlates with the disease state of tissue as determined by standard histochemical methods. Positive-ion data are presented which complement previously reported negative-ion data on paired human bladder cancerous and adjacent normal tissue sections from 20 patients. These data add to the evidence already in the literature demonstrating that differences in the distributions of particular lipids contain disease-diagnostic information. Multivariate statistical analysis using principal component analysis (PCA) is used to analyze the imaging MS data, and so confirm differences between the lipid profiles of diseased and healthy tissue types. As more such data is acquired, DESI imaging has the potential to be a diagnostic tool for future cancer detection in situ; this suggests a potential role in guiding therapy in parallel with standard histochemical and immunohistological methods. The PS methodology is aimed at high-throughput clinical measurement of quantitative levels of particular therapeutic agents in blood and other biofluids. The experiment allows individual drugs to be quantified at therapeutic levels and data is presented showing quantitative drug analysis from mixtures of therapeutic drugs in whole blood. Data on cholesterol sulfate, a new possible prostate biomarker seen at elevated levels in diseased prostate tissue, but not in healthy prostate tissue in serum are reported using paper spray ionization.
Adhesion Forces of the Blood Plasma Proteins on Self-Assembled Monolayer Surfaces of Alkanethiolates with Different Functional Groups Measured by an Atomic Force Microscope (1999)

To determine the adhesion force of representative blood plasma proteins (albumin (Alb), immunoglobulin G (IgG), and fibrinogen (Fib)) to foreign material surfaces, force-versus-distance curves were measured using an atomic force microscope (AFM) between the protein covalently immobilized AFM tips and the well-defined model surfaces of self-assembled monolayers (SAMs) of alkanethiolates terminated with different functional groups (CH3, NH2, OH, and COOH). From the f−d curves measured between the protein-immobilized tip and the SAM surface, the mechanical adhesion forces of the protein to the SAM surface (detachment force of protein from the surface) were determined. From the adhesion forces determined between the protein tip and the SAM surface and between like SAM-coated tips and surfaces (i.e., tip/surface combinations: CH3/CH3, NH2/NH2, OH/OH, and COOH/COOH), the thermodynamic adhesion strength (work of adhesion and surface pressure of SAM on a protein surface) was also determined according to the Dupré equation and Johnson, Kendall, and Roberts adhesion theory. The relative strength of thermodynamic adhesion of the proteins to the SAM surfaces was found with statistical significance to be in the following orders: (a) For Alb and IgG, CH3- ≫ (OH-, NH2-) > COOH-SAM surface; for Fib, CH3 ≫ OH > NH2 > COOH. (b) On CH3-, NH2-, and OH-SAM surfaces, Fib exhibits higher adhesion than Alb and IgG.
Studies on the mechanism of cartilage degradation (1984)

An in vivo study of cartilage breakdown in mice was carried out by implanting living and dead, intact or finely minced autologous cartilage back into newly elicited inflammatory tissue of the original donor. At various time intervals, the implants were removed and their loss of proteoglycan and collagen analysed both histologically and biochemically. The results show that only a modest loss of proteoglycan and collagen occurs in the living intact cartilage. Severe loss of proteoglycan was detected in the minced living and dead intact cartilage. The present findings clearly demonstrate that mechanical damage during the mincing of cartilage predisposes this tissue to attack by various types of mediators known to degrade cartilage.
Naturally Acquired Passive Protective Activity against Neisseria meningitidis Group C in the Absence of Serum Bactericidal Activity (2004)

The hallmark of immunity to meningococcal disease is a bactericidal titer in serum of > or =1:4 measured with human complement, but this threshold titer may underestimate the extent of protection. We used the infant rat model of meningococcal bacteremia to measure group C passive protective activity in serum samples from 91 unimmunized adults living in California. A total of 35 sera (38.5%) had passive protective activity. Sera with complement-mediated bactericidal titers of > or =1:4 were 3.4-fold more likely to confer protection (89%) than nonbactericidal sera (26%; P < 0.0001). Thus, bactericidal titers of > or =1:4 are a marker of protection, but this threshold lacks sensitivity for predicting protective activity. We investigated the 73 sera with bactericidal titers of <1:4 to determine the basis of protective activity. The 19 sera with protective activity had a higher geometric mean group C anticapsular antibody concentration (0.72 microg/ml) than the 54 sera that lacked protective activity (0.16 microg/ml; P < 0.001). Thus, protective activity in the absence of bactericidal activity was associated with higher concentrations of anticapsular antibodies, but not all sera with anticapsular antibodies conferred protection. Of 18 nonbactericidal sera with anticapsular antibody concentrations between 0.31 and 0.99 microg/ml, the 11 sera that conferred protection had a higher mean antibody avidity constant (21.9 nM(-1)) than the 7 nonprotective sera (14.6 nM(-1); P < 0.03). Thus, in sera with titers of <1:4, protective activity is associated with higher-avidity group C anticapsular antibodies, which are present in concentrations insufficient to elicit complement-mediated bacteriolysis in vitro but sufficient to confer protection in an in vivo bacteremia model.
A Perovskite Oxide Optimized for Oxygen Evolution Catalysis from Molecular Orbital Principles (2011)

The efficiency of many energy storage technologies, such as rechargeable metal-air batteries and hydrogen production from water splitting, is limited by the slow kinetics of the oxygen evolution reaction (OER). We found that Ba(0.5)Sr(0.5)Co(0.8)Fe(0.2)O(3-δ) (BSCF) catalyzes the OER with intrinsic activity that is at least an order of magnitude higher than that of the state-of-the-art iridium oxide catalyst in alkaline media. The high activity of BSCF was predicted from a design principle established by systematic examination of more than 10 transition metal oxides, which showed that the intrinsic OER activity exhibits a volcano-shaped dependence on the occupancy of the 3d electron with an e(g) symmetry of surface transition metal cations in an oxide. The peak OER activity was predicted to be at an e(g) occupancy close to unity, with high covalency of transition metal-oxygen bonds.
Interaction of a Mitogen-Activated Protein Kinase Signaling Module with the Neuronal Protein JIP3 (2000)

The c-Jun NH(2)-terminal kinase (JNK) group of mitogen-activated protein kinases (MAPKs) is activated in response to the treatment of cells with inflammatory cytokines and by exposure to environmental stress. JNK activation is mediated by a protein kinase cascade composed of a MAPK kinase and a MAPK kinase kinase. Here we describe the molecular cloning of a putative molecular scaffold protein, JIP3, that binds the protein kinase components of a JNK signaling module and facilitates JNK activation in cultured cells. JIP3 is expressed in the brain and at lower levels in the heart and other tissues. Immunofluorescence analysis demonstrated that JIP3 was present in the cytoplasm and accumulated in the growth cones of developing neurites. JIP3 is a member of a novel class of putative MAPK scaffold proteins that may regulate signal transduction by the JNK pathway.
Staphylococcal protein A simultaneously interacts with framework region 1, complementarity-determining region 2, and framework region 3 on human VH3-encoded Igs (1996)

Staphylococcal protein A (SPA) is a B cell superantigen that binds to human VH3-encoded Igs independently of the D- and JH-encoded regions and light chain sequences. The SPA-binding structure formed by VH3-encoded Igs remains controversial. We localized the regions in a VH3-encoded Ab required for SPA binding by producing mutant Abs in the baculovirus expression system in which regions of a human-derived Ab known to bind SPA were exchanged with those from a mouse Ab of the J558 family, a family not associated with SPA binding. The pattern of SPA binding indicates not only that residues in FR1, CDR2, and FR3 are involved but also that the three regions are required to interact simultaneously with SPA for binding to occur. When any one of the three regions was replaced with the corresponding region from the nonbinding Ab, SPA binding was severely disrupted. These data indicate that SPA requires simultaneous interaction with three distinct regions of a VH3 structure, which together in three-dimensional space form an extended solvent-exposed surface. These studies more precisely define the genetic requirements for VH3-encoded Ig binding to SPA.