gebhart/patrepeval huggingface dataset:
Phosphorylation of Y845 on the Epidermal Growth Factor Receptor Mediates Binding to the Mitochondrial Protein Cytochrome c Oxidase Subunit II (2004)

When co-overexpressed, the epidermal growth factor receptor (EGFR) and c-Src cooperate to cause synergistic increases in EGF-induced DNA synthesis, soft agar colony growth, and tumor formation in nude mice. This synergy is dependent upon c-Src-mediated phosphorylation of a unique tyrosine on the EGFR, namely, tyrosine 845 (Y845). Phenylalanine substitution of Y845 (Y845F) was found to inhibit EGF-induced DNA synthesis without affecting the catalytic activity of the receptor or its ability to phosphorylate Shc or activate mitogen-activated protein kinase. These results suggest that synergism may occur through alternate signaling pathways mediated by phosphorylated Y845 (pY845). One such pathway involves the transcription factor Stat5b. Here we describe another pathway that involves cytochrome c oxidase subunit II (CoxII). CoxII was identified as a specific binding partner of a pY845-containing peptide in a phage display screen. EGF-dependent binding of CoxII to the wild type but not to the mutant Y845F-EGFR was confirmed by coimmunoprecipitation experiments. This association also required the kinase activity of c-Src. Confocal microscopy, as well as biochemical fractionation, indicated that the EGFR translocates to the mitochondria after EGF stimulation, where it colocalizes with CoxII. Such translocation required the catalytic activity of the receptor but not phosphorylation of Y845. However, ectopic expression of the Y845F-EGFR prevented the EGF from protecting MDA-MB-231 breast cancer cells from adriamycin-induced apoptosis, whereas two mutants of Stat5b, a dominant-interfering mutant (DNstat5b) and a tyrosine mutation at 699 (Y699F-Stat5b) did not. Taken together, these data suggest that, through the ability of EGFR to translocate to the mitochondria, the binding of proteins such as CoxII to pY845 on the EGFR may positively regulate survival pathways that contribute to oncogenesis.
Fiber in the Treatment and Maintenance of Inflammatory Bowel Disease (2014)

There is limited weak evidence for the efficacy of fiber in improving disease outcomes in UC and pouchitis. The potential antiinflammatory role of fiber is intriguing and merits further investigation in adequately powered clinical trials. Excluding overt gastrointestinal obstruction, there was no evidence that fiber intake should be restricted in patients with inflammatory bowel disease.
Synthesis and Characterization of a Novel Liver-Targeted Prodrug of Cytosine-1-β-d-arabinofuranoside Monophosphate for the Treatment of Hepatocellular Carcinoma (2006)

Cytotoxic nucleosides have proven to be ineffective for the treatment of hepatocellular carcinoma (HCC) due, in part, to their inadequate conversion to their active nucleoside triphosphates (NTP) in the liver tumor and high conversion in other tissues. These characteristics lead to poor efficacy, high toxicity, and a drug class associated with an unacceptable therapeutic index. Cyclic 1-aryl-1,3-propanyl phosphate prodrugs selectively release the monophosphate of a nucleoside (NMP) into CYP3A4-expressing cells, such as hepatocytes, while leaving the prodrug intact in plasma and extrahepatic tissues. This prodrug strategy was applied to the monophosphate of the well-known cytotoxic nucleoside cytosine-1-beta-D-arabinofuranoside (cytarabine, araC). Compound 19S (MB07133), in mice, achieves good liver targeting compared to araC, generating >19-fold higher cytarabine triphosphate (araCTP) levels in the liver than levels of araC in the plasma and >12-fold higher araCTP levels in the liver than in the bone marrow, representing a >120-fold and >28-fold improvement, respectively, over araC administration.
Tropism illuminated: Lymphocyte-based pathways blazed by lethal morbillivirus through the host immune system (2004)

The immunosuppressive properties of morbilliviruses including measles and canine distemper virus (CDV) are well known, but the host cells supporting infection are poorly characterized. To identify these cells, a recombinant CDV expressing green fluorescent protein was produced by reverse genetics based on a wild-type strain lethal for ferrets. This recombinant virus fully retained virulence and blazed three lymphocyte-based pathways through the immune system of its host: first, it infected rapidly and massively circulating B and T cells; second, it took over and damaged secondary lymphatic organs including spleen, lymph nodes, and gut-associated and mucosal lymphoid tissues; third, it infected most thymocytes. In contrast, replication in epithelial cells was initially not detectable, but substantial before host death. Thus, CDV initially infects lymphocytes and massively replicates therein, thereby causing immunosuppression and preparing systemic invasion and host escape.
Laser Lipolysis: Current Practices (2009)

Laser-assisted liposuction (LAL) is a recent innovation within the field of liposculpture. In addition to body contouring, the indications of LAL are skin retraction in areas of flaccidity and fat melting for challenging surgical cases including revisions, areas of dense fibrosity, and large-volume cases. A photothermal effect explains the effects of LAL on tissue, regardless of the wavelength used. Advantages of LAL include reduced bruising, edema, pain, and recovery time. Disadvantages are most often related to thermal effects on tissue, such as skin blistering. Currently, 3 wavelengths, 980, 1064, and 1320 nm, are Food and Drug Administration-approved for LAL. Comparative studies examining the safety and efficacy of LAL have appeared in the medical literature. Technical considerations, emerging technology, and future indications are important to the success and continued development of this procedure.
Determination of Equilibrium Dissociation Constants (2009)

This chapter contains sections titled: Introduction Kinetic-Based Dissociation Constant Determination by SPR-Based Technology Equilibrium-Based Dissociation Constant Determination by Fluorescence ELISA (FL-ELISA) Equilibrium-Based Dissociation Constant Determination by KinExA Equilibrium Dissociation Constant Determination for IgG to Whole Cells Precautions and Artifacts in KD Determination Conclusion References
Peroxisome Proliferator-Activated Receptors: Nuclear Control of Metabolism* (1999)

I. Introduction II. Molecular Aspects A. PPAR isotypes: identity, genomic organization and chromosomal localization B. DNA binding properties C. PPAR ligand-binding properties D. Alternative pathways for PPAR activation E. PPAR-mediated transactivation properties III. Physiological Aspects A. Differential expression of PPAR mRNAs B. PPAR target genes and functions in fatty acid metabolism C. PPARs and control of inflammatory responses D. PPARs and atherosclerosis E. PPARs and the development of the fetal epidermal permeability barrier F. PPARs, carcinogenesis, and control of the cell cycle IV. Conclusions
Selective Aerobic Oxidation of HMF to 2,5‐Diformylfuran on Covalent Triazine Frameworks‐Supported Ru Catalysts (2015)

The selective aerobic oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-diformylfuran has been performed under mild conditions at 80 °C and 20 bar of synthetic air in methyl t-butyl ether. Ru clusters supported on covalent triazine frameworks (CTFs) allowed excellent selectivity and superior catalytic activity compared to other support materials such as activated carbon, γ-Al2 O3 , hydrotalcite, or MgO. CTFs with varying pore size, specific surface area, and N content could be prepared from different monomers. The structural properties of the CTF materials influence the catalytic activity of Ru/CTF significantly in the aerobic oxidation of HMF, which emphasizes the superior activity of mesoporous CTFs. Recycling of the catalysts is challenging, but promising methods to maintain high catalytic activity were developed that facilitate only minor deactivation in five consecutive recycling experiments.
Collection and transfusion of blood and blood components in the United States, 1989 (1993)

To probe recent trends in transfusion practice and their effect on the adequacy of the national blood resource, transfusions and collections in the United States in 1989 were studied, by using data shared by the American Association of Blood Banks, the American Red Cross, and the Council of Community Blood Centers, together with results from a sample survey of the 3600 hospitals that were not members of the national organizations. Statistical methods were used to estimate national activities. The total US supply of blood in 1989 was 14,229,000 units, an increase of 1.2 percent over the supply in 1987. Red cell transfusions were 12,059,000 units. A total of 3,159,000 patients underwent transfusion with whole blood and/or red cells (mean, 3.8 units/patient). Preoperative autologous deposits of 655,000 units by 310,000 patients represented an increase of 65 percent over the level in 1987. However, only 356,000 units (54%) were transfused to the patients who preoperatively deposited them; of the remainder, 13,000 units were crossed over for transfusion to other patients, while 286,000 units were never used. Directed donations, 350,000 units, were provided for 130,000 intended recipients, but only 97,000 units (28%) were transfused to their intended recipients; of the balance, 59,000 units (17%) were crossed over and 194,000 units (55%) were never transfused. Total platelet transfusions were equivalent to 7,258,000 units in 1989, for an increase of 13.7 percent over totals in 1987.
HB‐107, a nonbacteriostatic fragment of the antimicrobial peptide cecropin B, accelerates murine wound repair (2004)

Antimicrobial peptides are essential to innate host defense as effectors of pathogen clearance and can modify host cell behaviors to promote wound repair. While these two functions appear interrelated, it is unclear whether the ability to aid in wound repair requires inherent antimicrobial function. We hypothesized that the influence of antimicrobial peptides on wound repair is not dependent on antimicrobial function. To explore this, we analyzed the microbial killing activity of peptide fragments and correlated this with the ability to influence wound repair in mice. HB-107, a peptide lacking antimicrobial activity and originally derived from the antimicrobial cecropin B, showed up to 64 percent improvement in wound repair compared to scrambled peptide and vehicle controls, an effect comparable to treatment with recombinant human platelet-derived growth factor-BB (formulated as Regranex). Wounds treated with HB-107 showed keratinocyte hyperplasia and increased leukocyte infiltration. Furthermore, HB-107 stimulated interleukin-8 secretion from cultured endothelial cells, an effect that may explain the increase in leukocyte migration. These findings confirm that antimicrobial peptides can function as effectors of cutaneous wound repair. Moreover, this study furthers our understanding of antimicrobial peptides by showing that their wound repair properties can be independent of antimicrobial function.
The power of story. (2002)

In this guest editorial, the author introduces the reader to the value of stories as a source of vision and inspiration for caregiving.
Muscle stem cells in development, regeneration, and disease (2006)

Somatic stem cell populations participate in the development and regeneration of their host tissues. Skeletal muscle is capable of complete regeneration due to stem cells that reside in skeletal muscle and nonmuscle stem cell populations. However, in severe myopathic diseases such as Duchenne Muscular Dystrophy, this regenerative capacity is exhausted. In the present review, studies will be examined that focus on the origin, gene expression, and coordinated regulation of stem cell populations to highlight the regenerative capacity of skeletal muscle and emphasize the challenges for this field. Intense interest has focused on cell-based therapies for chronic, debilitating myopathic diseases. Future studies that enhance our understanding of stem cell biology and repair mechanisms will provide a platform for therapeutic applications directed toward these chronic, life-threatening diseases.
Concept identification and presentation in the context of technical text summarization (2000)

We describe a method of text summarization that produces indicative-informative abstracts for technical papers. The abstracts are generated by a process of conceptual identification, topic extraction and re-generation. We have carried out an evaluation to assess indicativeness and text acceptability relying on human judgment. The results so far indicate good performance in both tasks when compared with other summarization technologies.
Anti-HIV-1 Activity of Combinations and Covalent Conjugates of Negatively Charged Human Serum Albumins (NCAs) and AZT (1999)

Negatively charged albumins (NCAs, with the prototypes Suc-HSA and Aco-HSA), modified proteins with a potent anti-HIV-1 activity in the nanomolar concentration range, were studied for several aspects of their antiviral mechanism. In addition we investigated the antiviral activity of combinations and covalent conjugates of these NCAs and the reverse transcriptase inhibitor AZT. Addition of NCAs to HIV-1-infected target cells in time-of-addition experiments could be delayed for 30 min after infection before significant loss of activity occurred. Syncytium formation of HIV-infected and uninfected T-cells was inhibited by the NCAs at concentrations of 1-4 microg/ml. The gp120-mediated virus/cell binding, however, was only inhibited by the NCAs at a 10-fold higher concentrations. The combined data are compatible with a preferential influence on virus/cell fusion. A subsynergistic activity against HIV-1 was observed with the non-covalent mixture of Aco-HSA and AZT. When AZT was covalently coupled to the NCAs, and added one hour after infection of the target cells, the anti-HIV-1 activity of NCA-AZTMP was diminished by only 2-6-fold, while this was diminished at least 120-fold for the NCAs. Furthermore the addition of NCA-AZTMP could be delayed up to at least 3 h after infection without loss of antiviral activity. It is concluded that AZT that was coupled to the NCAs significantly contributes to the overall antiviral activity of the conjugates leading to complementary effects. These results highlight the potential of using NCA-AZTMP as dual-targeting preparations against HIV-1 in which both the carrier and the coupled drug contribute to the therapeutic efficacy acting at a different level in the replication cycle.
Calorimetric Studies of Serum Transferrin and Ovotransferrin. Estimates of Domain Interactions, and Study of the Kinetic Complexities of Ferric Ion Binding (1994)

Human serum transferrin and hen ovotransferrin have been studied by differential scanning calorimetry (DSC), in an effort to quantitatively estimate the free energy of interaction of the N- and C-domains in each protein and to further understand their interaction with chelated ferric ions. In the case of serum transferrin, separate DSC transitions are observed for the two domains while only a single, coupled transition is seen for ovotransferrin. Although domain interactions are somewhat larger for ovotransferrin (-4100 cal/mol) than for serum transferrin (-3100 cal/mol), the major cause of separated transitions for serum transferrin is that the difference in intrinsic folding stability of the N- and C-domains is about 4-fold larger than for ovotransferrin. Chelated ferric ions bind strongly to each site in both proteins and produce changes in Tm by as much as 30 degrees C. When apparent binding constants are estimated from DSC results, these appear to be substantially larger than those estimated previously from equilibrium methods at low temperatures, where very long equilibrium times must be used because of slow ligand release. Although second DSC upscans on each protein show good "reversibility", downscans on serum transferrin revealed that liganded forms of the protein are in fact not in true equilibrium during upscanning, which causes Tm values during upscans to be higher than the true reversible Tm values. The likely reason for this kinetic control over unfolding is the slow release of bound ferric ions and those effects, for technical reasons, cannot be totally eliminated by lowering the scan rate.
The Ecology of J. J. Gibson's Perception (1981)

J. J. Gibson's approach to,the study of perception emphasizes the way an active observer picks up information from the environment. The central postulates of Gibson's approach are that (1) visual space is defined by information (such as texture gradients) contained on environmental surfaces, (2) the crucial information for perception is information that remains invariant as an observer moves through the environment, and (3) this invariant information is picked up directly, so that no intervening mental processes are necessary for visual perception. This paper summarizes Gibson's approach as it is stated in his three books, Perception of the Visual World (1950), The Senses Considered as Perceptual Systems (1966) and The Ecological Approach to Visual Perception (1979) and evaluates thefinalform of his approach described in his third, and last, book.
Circulating Bmi-1 mRNA as a possible prognostic factor for advanced breast cancer patients (2007)

Our results suggest that levels of Bmi-1 expression may be a surrogate marker of poor prognosis and may become clinically useful as noninvasive diagnostic markers.
Down- and up-conversion photoluminescence, cathodoluminescence and paramagnetic properties of NaGdF4 : Yb3+,Er3+ submicron disks assembled from primary nanocrystals (2010)

NaGdF4 : Yb3+,Er3+ submicron disks have been synthesized at a relatively low temperature in aqueous solution with citric acid as the structure-directing agent. The structure, luminescence, and magnetic properties of the synthesized materials have been characterized by a variety of techniques. The as-prepared NaGdF4 : Yb3+,Er3+ has hexagonal structure, and is mainly composed of submicron disks with a diameter of around 870 nm and a thickness of about 420 nm. Citrate groups selectively bonded to a certain crystal surface of the nanocrystals probably provide the driving force that makes primary particles assemble into submicron disks. The phase structure of these submicron disks is affected by the annealing temperature, while the disk morphology could be essentially preserved even when annealed at high temperatures. The annealed submicron disks exhibit prominent visible emission with different excitation sources, including ultraviolet light, low-voltage electron beam and near-infrared laser. In addition, these disks exhibit paramagnetic features with the mass magnetic susceptibility value of 9.82 × 10−5 emu/g·Oe at room temperature. These multifunctional disks would have potential in applications as building blocks for many functional devices such as solid-state lasers, lighting and displays, magnetic resonance imaging and so on.
Oxidized/misfolded superoxide dismutase‐1: the cause of all amyotrophic lateral sclerosis? (2007)

The identification in 1993 of superoxide dismutase-1 (SOD1) mutations as the cause of 10 to 20% of familial amyotrophic lateral sclerosis cases, which represents 1 to 2% of all amyotrophic lateral sclerosis (ALS) cases, prompted a substantial amount of research into the mechanisms of SOD1-mediated toxicity. Recent experiments have demonstrated that oxidation of wild-type SOD1 leads to its misfolding, causing it to gain many of the same toxic properties as mutant SOD1. In vitro studies of oxidized/misfolded SOD1 and in vivo studies of misfolded SOD1 have indicated that these protein species are selectively toxic to motor neurons, suggesting that oxidized/misfolded SOD1 could lead to ALS even in individuals who do not carry an SOD1 mutation. It has also been reported that glial cells secrete oxidized/misfolded mutant SOD1 to the extracellular environment, where it can trigger the selective death of motor neurons, offering a possible explanation for the noncell autonomous nature of mutant SOD1 toxicity and the rapid progression of disease once the first symptoms develop. Therefore, considering that sporadic (SALS) and familial ALS (FALS) cases are clinically indistinguishable, the toxic properties of mutated SOD1 are similar to that of oxidized/misfolded wild-type SOD1 (wtSOD1), and secreted/extracellular misfolded SOD1 is selectively toxic to motor neurons, we propose that oxidized/misfolded SOD1 is the cause of most forms of classic ALS and should be a prime target for the design of ALS treatments.
P-selectin glycoprotein ligand-1 (PSGL-1) is a ligand for L-selectin in neutrophil aggregation (1996)

In inflammation, activated neutrophils adhere to endothelial cells and aggregate with one another. While beta 2-integrin and L-selectin are essential for aggregation, their ligands remain to be identified. We have previously shown that L-selectin mediates a carbohydrate-dependent interaction in aggregation (Simon et al: J Immunol 149:2765, 1992; Rochon et al: J Immunol 152:1385, 1994). We have suggested that the L-selectin counter-structure is a mucinlike protein and proposed that aggregation occurs through a two-step process involving L-selectin, beta 2-integrin, and their distinct counter-structures (Bennett et al: J Leuk Biol 58:510, 1995). A candidate ligand for L-selectin is P-selectin glycoprotein ligand-1 (PSGL-1), a mucinlike protein on neutrophils that binds P-and E-selectin. Using flow cytometry we show that the number and size of neutrophil aggregates is reduced with Fab fragments of PL1, an anti-PSGL-1 monoclonal antibody that blocks the interaction between P-selectin and PSGL-1 (Moore et al: J Cell Biol 128:661, 1995). In addition, monoclonal antibodies to L-selectin and PSGL-1 were used simultaneously to modulate the availability of these adhesion molecules on individual cell populations. The inhibition of aggregation by these antibodies is consistent with L-selectin and PSGL-1 being counter-structures. We suggest that L-selectin and PSGL-1 support a collisional cell-cell interaction that represents the first step in neutrophil aggregation.
Characterization of Wild-Type and ΔF508 Cystic Fibrosis Transmembrane Regulator in Human Respiratory Epithelia (2005)

Previous studies in native tissues have produced conflicting data on the localization and metabolic fate of WT and deltaF508 cystic fibrosis transmembrane regulator (CFTR) in the lung. Combining immunocytochemical and biochemical studies utilizing new high-affinity CFTR mAbs with ion transport assays, we examined both 1) the cell type and region specific expression of CFTR in normal airways and 2) the metabolic fate of deltaF508 CFTR and associated ERM proteins in the cystic fibrosis lung. Studies of lungs from a large number of normal subjects revealed that WT CFTR protein localized to the apical membrane of ciliated cells within the superficial epithelium and gland ducts. In contrast, other cell types in the superficial, gland acinar, and alveolar epithelia expressed little WT CFTR protein. No deltaF508 CFTR mature protein or function could be detected in airway specimens freshly excised from a large number of deltaF508 homozygous subjects, despite an intact ERM complex. In sum, our data demonstrate that WT CFTR is predominantly expressed in ciliated cells, and deltaF508 CFTR pathogenesis in native tissues, like heterologous cells, reflects loss of normal protein processing.