gebhart/patrepeval huggingface dataset:
Dynamic Steiner Tree Problem (1991)

This paper proposes a new problem called the dynamic Steiner tree problem. Interest in the dynamic Steiner tree problem is motivated by multipoint routing in communication networks, where the set of nodes in the connection changes over time. This problem, which has its basis in the Steiner tree problem on graphs, can be divided into two cases: one in which rearrangement of existing routes is not allowed, and a second in which rearrangement is allowed. For the nonrearrangeable version, it is shown that the worst-case performance for any algorithm is at least $\frac{1}{2}\lg n$ times the cost of an optimum solution with complete rearrangement. Here n is the maximum number of nodes to be connected. In addition, a simple, polynomial time algorithm is present that has worst-case performance within two times this bound. In the rearrangeable case, a polynomial time algorithm is presented with worst-case performance bounded by a constant times optimum.
Imaging tissue response to electrical and photothermal stimulation with nanometer sensitivity (2003)

Since PS-OLCR is a useful tool to detect ultra-small path length changes, the system has potential to aid scientists in investigating important phenomena in biomaterials and developing useful diagnostic and therapeutic imaging modalities. Applications include tissue surface profilometry, measurement of tissue, and cell response to various stimuli, high-resolution intensity and phase imaging.
Nutritional toxicology of tannins and related polyphenols in forage legumes (1995)

Proanthocyanidins (PA) (condensed tannins) and hydrolyzable tannins (HT) are the two major classes of tannins. Proanthocyanidins are flavonoid polymers. Hydrolyzable tannins are polymers of gallic or ellagic acid esterified to a core molecule, commonly glucose or a polyphenol such as catechin. Proanthocyanidins are the most common type of tannin found in forage legumes. Problems in the analysis of tannins are that sample processing and drying decrease extraction and reactivity, suitable standards are unavailable, and quantitative analytical methods are poorly correlated with enzyme inhibition, protein precipitation, and nutritional effects. Hydrolyzable tannins are potentially toxic to ruminants. Pyrogallol, a hepatotoxin and nephrotoxin, is a product of HT degradation by ruminal microbes. Proanthocyanidins are considered to be non-toxic because they are not absorbed, but they are associated with lesions of the gut mucosa. Research on tannins in forage legumes has determined their effects on protein digestion and metabolism but more research on tannin structure in relation to digestion of specific proteins is needed. The widely accepted explanation for positive effects of PA on protein digestion and metabolism is that PA-protein complexes escape ruminal degradation and the protein is available in the lower tract. This proposed mechanism may be incorrect because PA also complex carbohydrates, endogenous proteins, and microbial products and the degradability of PA-protein complexes by ruminal microbes has not been adequately studied. Several alternative hypotheses (to escape protein) that explain the effect of PA on protein digestion and metabolism in ruminants are also consistent with experimental results on forage legumes. These include increased microbial protein synthesis, increased use of endogenous nitrogen in the rumen, and increased secretion of salivary glycoproteins. Research on manipulating the content and type of PA in forage legumes is justified because they are associated with non-bloating legumes, lower soluble non-protein nitrogen in silage, and improved efficiency of protein utilization. Research on the biosynthesis, molecular genetics, and cell biology of PA in forage legumes needs to be integrated with research on toxicology and nutrition.
Epidermal Growth Factor-Like Repeats Mediate Lateral and Reciprocal Interactions of Ep-CAM Molecules in Homophilic Adhesions (2001)

Ep-CAM is a new type of cell adhesion molecule (CAM) which does not structurally resemble the members of the four major families (cadherins, integrins, selectins, and CAMs of the immunoglobulin superfamily) and mediates Ca(2+)-independent, homophilic adhesions. The extracellular domain of Ep-CAM consists of a cysteine-rich region, containing two type II epidermal growth factor (EGF)-like repeats, followed by a cysteine-poor region. We generated mutated Ep-CAM forms with various deletions in the extracellular domain. These deletion mutants, together with monoclonal antibodies recognizing different epitopes in the extracellular domain, were used to investigate the role of the EGF-like repeats in the formation of intercellular contacts mediated by Ep-CAM molecules. We established that both EGF-like repeats are required for the formation of Ep-CAM-mediated homophilic adhesions, including the accumulation of Ep-CAM molecules at the cell-cell boundaries, and the anchorage of the Ep-CAM adhesion complex to F-actin via alpha-actinin. Deletion of either EGF-like repeat was sufficient to inhibit the adhesion properties of the molecule. The first EGF-like repeat of Ep-CAM is required for reciprocal interactions between Ep-CAM molecules on adjacent cells, as was demonstrated with blocking antibodies. The second EGF-like repeat was mainly required for lateral interactions between Ep-CAM molecules. Lateral interactions between Ep-CAM molecules result in the formation of tetramers, which might be the first and necessary step in the formation of Ep-CAM-mediated intercellular contacts.
Thrombospondin-1 binds to polyhistidine with high affinity and specificity (2000)

Thrombospondin-1 (TSP1) is a secreted trimeric glycoprotein of 450 kDa with demonstrated effects on cell growth, adhesion and migration. Its complex biological activity is attributed to its ability to bind to cell-surface receptors, growth factors and extracellular-matrix proteins. In this study, we used a 125I solid-phase binding assay to demonstrate that TSP1 binds specifically to proteins containing polyhistidine stretches. Based on studies with three different six-histidine-containing recombinant proteins, we derived an average dissociation constant of 5 nM. The binding of 125I-labelled TSP1 to these proteins was inhibited by peptides containing histidine residues, with the degree of competition being a function of the number of histidines within the peptide. Binding was not inhibited by excess histidine or imidazole, indicating that the imidazole ring is not sufficient for recognition by TSP1. Heparin was a potent inhibitor of binding with a Ki of 50 nM, suggesting that the heparin-binding domain of TSP1 may be involved in this interaction. This was confirmed by the ability of a recombinant heparin-binding domain of TSP1 to directly compete for TSP1 binding to polyhistidine-containing proteins. Affinity chromatography with a polyhistidine-containing peptide immobilized on agarose revealed that TSP1 in platelet releasates is the major polypeptide retained on the six-histidine-peptide column. We conclude that TSP1 contains a high-affinity binding site for polyhistidine and this is likely to be the molecular basis for the observed binding of TSP1 to histidine-rich glycoprotein. The possibility that other polyhistidine-containing proteins also interact with TSP1 warrants further study.
Techniques in Cell Cycle Analysis (1987)

Quantification of the proliferative characteristics of normal and malignant cells has been of interest to oncolo gists and cancer biologists for almost three decades. This interest stems from (a) the
An optimized approach for enrichment of glycoproteins from cell culture lysates using native multi‐lectin affinity chromatography (2012)

Lectins are capable of recognizing specific glycan structures and serve as invaluable tools for the separation of glycosylated proteins from nonglycosylated proteins in biological samples. We report on the optimization of native multi-lectin affinity chromatography, combining three lectins, namely, concanavalin A, jacalin, and wheat germ agglutinin for fractionation of cellular glycoproteins from MCF-7 breast cancer lysate. We evaluated several conditions for optimum recovery of total proteins and glycoproteins such as low pH and saccharide elution buffers, and the inclusion of detergents in binding and elution buffers. Optimum recovery was observed with overnight incubation of cell lysate with lectins at 4°C, and inclusion of detergent in binding and saccharide elution buffers. Total protein and bound recoveries were 80 and 9%, respectively. Importantly, we found that high saccharide strength elution buffers were not necessary to release bound glycoproteins. This study demonstrates that multi-lectin affinity chromatography can be extended to total cell lysate to investigate the cellular glycoproteome.
Angiogenesis in cancer (2006)

New growth in the vascular network is important since the proliferation, as well as metastatic spread, of cancer cells depends on an adequate supply of oxygen and nutrients and the removal of waste products. New blood and lymphatic vessels form through processes called angiogenesis and lymphangiogenesis, respectively. Angiogenesis is regulated by both activator and inhibitor molecules. More than a dozen different proteins have been identified as angiogenic activators and inhibitors. Levels of expression of angiogenic factors reflect the aggressiveness of tumor cells. The discovery of angiogenic inhibitors should help to reduce both morbidity and mortality from carcinomas. Thousands of patients have received antiangiogenic therapy to date. Despite their theoretical efficacy, antiangiogeic treatments have not proved beneficial in terms of long-term survival. There is an urgent need for a new comprehensive treatment strategy combining antiangiogenic agents with conventional cytoreductive treatments in the control of cancer.
Etv2 rescues Flk1 mutant embryoid bodies (2013)

Independent mouse knockouts of Etv2 and Flk1 are embryonic lethal and lack hematopoietic and endothelial lineages. We previously reported that Flk1 activates Etv2 in the initiation of hematopoiesis and vasculogenesis. However, Flk1 and its ligand VEGF are expressed throughout development, from E7.0 to adulthood, whereas Etv2 is expressed only transiently during embryogenesis. These observations suggest a complex regulatory interaction between Flk1 and Etv2. To further examine the Flk1 and Etv2 regulatory interaction, we transduced Etv2 and Flk1 mutant ES cells with viral integrants that inducibly overexpress Flk1 or Etv2. We demonstrated that forced expression of Etv2 rescued the hematopoietic and endothelial potential of differentiating Flk1 and Etv2 mutant cells. We further discovered that forced expression of Flk1 can rescue that of the Flk1, but not Etv2 mutant cells. Therefore, we conclude that the requirement for Flk1 can be bypassed by expressing Etv2, supporting the notion that disruption of Etv2 expression is responsible for the early phenotypes of the Etv2 and Flk1 mutant embryos.
Nonenzymatic Glucose Detection Using Mesoporous Platinum (2003)

Roughness of nanoscopic dimensions can be used to selectively enhance the faradaic current of a sluggish reaction. Using this principle, we constructed mesoporous structures on the surfaces of pure platinum electrodes responding even more sensitively to glucose than to common interfering species, such as L-ascorbic acid and 4-acetamidophenol. Good sensitivities, as high as 9.6 microA cm(-2) mM(-1), were reproducibly observed in the presence of high concentration of chloride ion. The selectivities, sensitivities, and stabilities determined experimentally have demonstrated the potential of mesoporous platinum as a novel candidate for nonenzymatic glucose sensors.
Increased risk of skin cancer associated with the presence of epidermodysplasia verruciformis human papillomavirus types in normal skin (2004)

HPV DNA is widespread in normal adult skin, particularly in transplant patients. In our study, the presence of EV but not cutaneous HPV DNA in normal skin was significantly associated with NMSC status and may prove to be of predictive value for skin cancer risk. These data provide reason to focus on EV HPV types as causal agents in skin cancer.
DNA Sequencing by Mass Spectrometry (1996)

Mass spectrometry has the potential to replace gel electrophoresis for fast DNA sequencing. In this tutorial paper, it is discussed how far mass spectrometry of DNA has come since the advent of electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) and how much remains to be done before mass spectrometry will be a useful tool for DNA sequencing. A brief description of MALDI and ESI mass spectrometric analysis of DNA is presented along with the different strategies for DNA sequencing using mass spectrometry. These include mass spectrometric analysis to replace gel separation in Sanger sequencing, enzymatic ladder sequencing and sequencing by gas-phase fragmentation. The future role of mass spectrometry in DNA sequencing in the Human Genome Project and beyond is also discussed.
Coacervation Characteristics of Recombinant Human Tropoelastin (1997)

Coacervation of soluble tropoelastin molecules is characterized by thermodynamically reversible association as temperature is increased under appropriately juxtaposed ionic conditions, protein concentration and pH. Coacervation plays a critical role in the assembly of these elastin precursors in elastic fiber formation. To examine the effect of physiological parameters on the ability of tropoelastin molecules to associate, solutions of recombinant human tropoelastin were monitored spectrophotometrically by light scattering over a broad range of temperatures. Coacervation of recombinant human tropoelastin is strongly influenced by the concentration of protein and NaCl and to a lesser extent on pH. Trends towards maximal association are apparent when each of these parameters is varied. Remarkably, optimal coacervation is found at 37 degrees C, 150 mM NaCl and pH 7-8. Using the data generated by time courses, estimates of thermodynamic parameters were made. These estimates confirm that coacervation is endothermic and is marked by a strong entropic contribution. Circular dichroism of recombinant human tropoelastin revealed that, rather than being random, the structure is compatible with being largely that, of an all-beta protein (with secondary structure estimated to be 3% alpha-helix, 41% beta-sheet, 21% beta-turn and 33% other), exhibiting a spectrum as previously seen for tropoelastin populations and soluble elastin from naturally-derived sources.
Job Scheduling for Multi-User MapReduce Clusters (2009)

Sharing a MapReduce cluster between users is attractive because it enables statistical multiplexing (lowering costs) and allows users to share a common large data set. However, we find that traditional scheduling algorithms can perform very poorly in MapReduce due to two aspects of the MapReduce setting: the need for data locality (running computation where the data is) and the dependence between map and reduce tasks. We illustrate these problems through our experience designing a fair scheduler for MapReduce at Facebook, which runs a 600-node multi-user data warehouse on Hadoop. We developed two simple techniques, delay scheduling and copy-compute splitting, which improve throughput and response times by factors of 2 to 10. Although we focus on multi-user workloads, our techniques can also raise throughput in a single-user, FIFO workload by a factor of 2.
Secretory phospholipase A2and phospholipids in neural membranes in an experimental epilepsy model (2002)

Our results suggest that epileptic seizures enhanced phospholipid breakdown and induced alterations in the distribution of phospholipids in different brain regions.
Identification of chloroplast envelope proteins in close physical proximity to a partially translocated chimeric precursor protein. (1994)

Translocation intermediates of the chimeric protein precursor Oee1-Dhfr were generated and used to identify envelope components in close proximity to the arrested precursor. The translocation of Oee1-Dhfr across the chloroplast envelope can be arrested at low ATP levels or by prebinding the fusion precursor with anti-Dhfr IgGs. The arrested Oee1-Dhfr precursor appears to span both the outer and inner envelope membranes. Translocational arrest of Oee1-Dhfr by low ATP levels was reversible, and import was restored upon resupplementation with higher ATP levels. Chemical cross-linking and co-immunoprecipitation with monospecific antibodies indicate that two outer envelope membrane proteins (Com44 and Com70) and at least one inner envelope protein (Cim44 and Cim97) were found to be in close proximity to Oee1-Dhfr during translocation. The Com70 protein was further studied and additional evidence for its role in chloroplast protein import is presented.
rAAV2 traffics through both the late and the recycling endosomes in a dose-dependent fashion (2006)

Inefficient trafficking of recombinant adeno-associated virus type-2 (rAAV2) to the nucleus is a major barrier for transduction. Using imaging and subcellular fractionation techniques, we evaluated the extent of rAAV2 movement through the late (Rab7) and recycling (Rab11) endosomes. Following rAAV2 infection of HeLa cells, immunoisolation of HA-Rab7- or HA-Rab11-tagged endosomes and intracellular colocalization of Cy3-labeled rAAV2 with EGFP-Rab7 or EGFP-Rab11 markers demonstrated dose-dependent trafficking of rAAV2 through the recycling and late endosomal compartments. At low multiplicities of infection (m.o.i. 100 genomes/cell), rAAV2 predominantly trafficked to the Rab7 compartment. In contrast, rAAV2 predominantly trafficked to the recycling endosome at 100-fold higher m.o.i. siRNA studies inhibiting either Rab7 or Rab11 demonstrated that reducing Rab11 protein levels more significantly inhibited rAAV2 transduction on a per genome basis compared to inhibition of Rab7. Dose-response curves, comparing the m.o.i. of AV2Luc infection to relative transduction, also supported the hypothesis that viral movement through the Rab11 compartment at high m.o.i. is more competent for transgene expression ( approximately 100-fold) than virus that moves through the Rab7 compartment at low m.o.i. These findings suggest that strategies to shunt viral movement from the late to the recycling endosome may be effective at increasing viral transduction for gene therapy.
Influence of gel properties on neocartilage formation by auricular chondrocytes photoencapsulated in hyaluronic acid networks (2006)

The objective of this study was to determine how changes in the network structure and properties of hyaluronic acid (HA) hydrogels, due to variations in the macromer molecular weight (50-1,100 kDa) and macromer concentration (2-20 wt %), affect neocartilage formation by encapsulated auricular chondrocytes. To investigate tissue formation, swine auricular chondrocytes were photoencapsulated in the various networks, implanted subcutaneously in the dorsum of nude mice, and explanted after 6 and 12 weeks for biochemical and histological analysis. After 12 weeks, the various constructs were 81-93% water, contained between 0.1 x 10(6) and 0.6 x 10(6) chondrocytes per sample, and consisted of 0-0.049 microg chondroitin sulfate/mug wet weight (glycosaminoglycan (GAG) content) and 0.002-0.060 microg collagen/microg wet weight. Histological staining showed an even distribution of chondrocytes and GAGs in addition to minimal type I collagen staining and intense and uniform type II collagen staining in the constructs with greatest neocartilage production. Hydrogels fabricated from 2 wt % of the 50 kDa HA macromer most resembled the properties of native cartilage and show the greatest promise for continued development for cartilage regeneration.
Characterization of Novel Vascular Endothelial Growth Factor (VEGF) Receptors on Tumor Cells That Bind VEGF165 via Its Exon 7-encoded Domain (1996)

Vascular endothelial growth factor (VEGF), a potent angiogenic factor, uses two receptor tyrosine kinases, FLK/KDR and FLT, to mediate its activities. We have cross-linked 125I-VEGF165 to the cell surface of various tumor cell lines and of human umbilical vein endothelial cells. High molecular mass (220 and 240 kDa) and/or lower molecular mass (165 and 175 kDa) labeled complexes were detected depending on the cell type. The 220- and 240-kDa labeled complexes were shown to contain FLT and FLK/KDR receptors, respectively. On the other hand, the 165- and 175-kDa complexes did not seem to contain FLK/KDR or FLT but instead appeared to contain novel VEGF receptors with relatively low molecular masses of approximately 120 and 130 kDa. These receptors were further characterized in breast cancer MDA MB 231 cells (231), which did not form the high molecular mass complexes and which did not express detectable amounts of flk/kdr or flt mRNA. The 231 cells displayed one VEGF165 binding site, with a Kd of 2.8 x 10(-10) M and 0.95 1.1 x 10(5) binding sites per cell. By comparison, human umbilical vein endothelial cells had two binding sites, one with a Kd of 7.5 x 10(-12) M, presumably FLK/KDR, and the other with a Kd of 2 x 10(-10) M, a value similar to the VEGF binding sites on 231 cells. These lower affinity/molecular mass receptors on 231 cells cross-linked 125I-VEGF165 but not 125I-VEGF121. Accordingly, exon 7 of VEGF, which encodes the 44 amino acids present in VEGF165 that are absent in VEGF121, was fused to glutathione S-transferase (GST). The GST-VEGF-exon 7 fusion protein bound to heparin-Sepharose with a similar affinity as VEGF165 and inhibited the binding of 125I-VEGF165 to 231 cells. Cross-linking of 125I-GST-VEGF-exon 7 to 231 cells resulted in the formation of 150- and 160-kDa labeled complexes that presumably contained the 120- and 130-kDa lower affinity/molecular mass VEGF165 receptors. It was concluded that certain tumor-derived cell lines express novel surface-associated receptors that selectively bind VEGF165 via the exon 7-encoded domain, which is absent in VEGF121.
MicroRNA miR-199a* Regulates the MET Proto-oncogene and the Downstream Extracellular Signal-regulated Kinase 2 (ERK2) (2008)

MicroRNAs (miRNAs) constitute a class of small noncoding RNAs that play important roles in a variety of biological processes including development, apoptosis, proliferation, and differentiation. Here we show that the expression of miR-199a and miR-199a* (miR-199a/a*), which are processed from the same precursor, is confined to fibroblast cells among cultured cell lines. The fibroblast-specific expression pattern correlated well with methylation patterns: gene loci on chromosome 1 and 19 were fully methylated in all examined cell lines but unmethylated in fibroblasts. Transfection of miR-199a and/or -199a* mimetics into several cancer cell lines caused prominent apoptosis with miR-199a* being more pro-apoptotic. The mechanism underlying apoptosis induced by miR-199a was caspase-dependent, whereas a caspase-independent pathway was involved in apoptosis induced by miR-199a* in A549 cells. By employing microarray and immunoblotting analyses, we identified the MET proto-oncogene as a target of miR-199a*. Studies with a luciferase reporter fused to the 3'-untranslated region of the MET gene demonstrated miR-199a*-mediated down-regulation of luciferase activity through a binding site of miR-199a*. Interestingly, extracellular signal-regulated kinase 2 (ERK2) was also down-regulated by miR-199a*. Coordinated down-regulation of both MET and its downstream effector ERK2 by miR-199a* may be effective in inhibiting not only cell proliferation but also motility and invasive capabilities of tumor cells.