gebhart/patrepeval huggingface dataset:
Purification of an inhibitor of plasminogen activator (antiactivator) synthesized by endothelial cells. (1984)

Cultured bovine aortic endothelial cells are associated with an unusually stable fibrinolytic inhibitor (Loskutoff, D.J., van Mourik, J.A., Erickson, L.A., and Lawrence, D. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 2956-2960). This inhibitor was purified to apparent homogeneity from medium conditioned by these cells by a combination of concanavalin A affinity chromatography and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It is a single-chain glycoprotein of apparent Mr 50,000 +/- 2,500 and isoelectric point of 4.5-5.0, and inhibits the ability of both urokinase and tissue-type plasminogen activator to cleave and active plasminogen. This inhibition of plasminogen activator activity is associated with the formation of an enzyme-inhibitor complex which can be detected after polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The purified inhibitor retains full activity after incubation in the presence of 0.1% sodium dodecyl sulfate, or at pH 2.7, two treatments which rapidly destroy the activity of protease nexin, another cellular inhibitor of fibrinolysis. The inhibitor purified from cloned endothelial cells cultured in the presence of L-[3,4,5-3H]leucine represented 2.5-12% of the total radiolabeled protein released by the cells in a 24-h period. These results indicate that cultured bovine aortic endothelial cells synthesize and secrete a protein which inhibits plasminogen activators and is distinct from protease nexin. It is a major endothelial cell product, and, as such, probably plays an important role in regulating the fibrinolytic system of these cells.
Municipal Solid Waste Collection Route Optimization Using Geospatial Techniques: A Case Study of Two Metropolitan Cities of Pakistan (2016)

The population growth in many urban cities and its activities in developing countries have resulted in an increased solid waste generation rate and waste management has become a global environmental issue. Routing of solid waste collection vehicles in developing countries like Pakistan poses a challenging task. In the process of solid waste management, collection and transportation play a leading role in waste collection and disposal, in which collection activities contributed the most to total cost for solid waste collection activities. Therefore, this study describes an attempt to design and develop an appropriate collection, transportation and disposal plan for the twin cities of Pakistan by using Geographic Information System (GIS) and Remote Sensing (RS) techniques to determine the minimum cost/distance/time efficient collection paths for the transportation of the solid wastes to the landfill sites.&#13;\nIn addition to this, identification of solid waste disposal sites and appropriately managing them is a challenging task to many developing countries and Pakistan is no exception to that. The existing landfill sites for the twin cities are not technically viable and environmentally acceptable and are thus damaging to the environment due to their location and the type of waste dumped. Therefore, the second aim of our study was to find out the suitable landfill sites for the twin cities and the study employed Multi-Criteria Evaluation (MCE) methods to combine necessary factors considered for landfill site selection for the twin cities. Hence, our present study has proved that GIS is a tool that can be used in integration with other techniques such as MCE for a identifying new landfill sites and it can help decision makers deal with real-world developmental and management issues.&#13;\nFinally, the study has developed a Wed-Based Decision Support System (DSS) via Application Programming Interface (API) which will help decision-makers to search for cost-effective alternatives and it can be operated by people who don?t have knowledge of GIS. The proposed study can be used as a decision support tool by the municipalities of the twin cities for efficient management and transportation of solid wastes to landfill sites, managing work schedules for workers, etc.
α-Lactalbumin (LA) Stimulates Milk β-1,4-Galactosyltransferase I (β4Gal-T1) to Transfer Glucose from UDP-glucose to N-Acetylglucosamine (2001)

beta-1,4-Galactosyltransferase 1 (Gal-T1) transfers galactose (Gal) from UDP-Gal to N-acetylglucosamine (GlcNAc), which constitutes its normal galactosyltransferase (Gal-T) activity. In the presence of alpha-lactalbumin (LA), it transfers Gal to Glc, which is its lactose synthase (LS) activity. It also transfers glucose (Glc) from UDP-Glc to GlcNAc, constituting the glucosyltransferase (Glc-T) activity, albeit at an efficiency of only 0.3-0.4% of Gal-T activity. In the present study, we show that LA increases this activity almost 30-fold. It also enhances the Glc-T activity toward various N-acyl substituted glucosamine acceptors. Steady state kinetic studies of Glc-T reaction show that the K(m) for the donor and acceptor substrates are high in the absence of LA. In the presence of LA, the K(m) for the acceptor substrate is reduced 30-fold, whereas for UDP-Glc it is reduced only 5-fold. In order to understand this property, we have determined the crystal structures of the Gal-T1.LA complex with UDP-Glc x Mn(2+) and with N-butanoyl-glucosamine (N-butanoyl-GlcN), a preferred sugar acceptor in the Glc-T activity. The crystal structures reveal that although the binding of UDP-Glc is quite similar to UDP-Gal, there are few significant differences observed in the hydrogen bonding interactions between UDP-Glc and Gal-T1. Based on the present kinetic and crystal structural studies, a possible explanation for the role of LA in the Glc-T activity has been proposed.
Ethical and legal considerations regarding the ownership and commercial use of human biological materials and their derivatives (2012)

This article considers some of the ethical and legal issues relating to the ownership and use - including for commercial purposes - of biological material and products derived from humans. The discussion is divided into three parts: after first examining the general notion of ownership, it moves to the particular case of possible commercial use, and finally reflects on the case in point in the light of the preceding considerations. Units of cord blood donated altruistically for transplantation and which are found unsuitable for storage and transplantation, or which become unsuitable while stored in biobanks, are taken as an example. These cord-blood units can be discarded together with other biological waste, or they can be used for research or the development of blood-derived products such as platelet gel. Several ethical questions (eg, informed consent, property, distribution of profits, and others) arise from these circumstances. In this regard, some criteria and limits to use are proposed.
Atypical lobular hyperplasia and lobular carcinoma in situ: surgical and molecular pathology (1999)

Lobular carcinoma in situ and atypical lobular hyperplasia were first described over 50 years ago. Despite this long incubation period, the biological nature of the lesions remains controversial. They are generally regarded as 'risk indicators' of invasive cancer rather than true precursor lesions. When first described, the 'carcinoma in situ' designation implied radical treatment in the form of a mastectomy. Subsequent observation has shown that the lesions are often multifocal and bilateral. The risk to the woman of developing invasive cancer after a diagnosis of lobular carcinoma in situ is small. Hence, the lesion has increasingly been regarded as a 'hyperplastic' proliferation, which although predicting for subsequent risk of invasive cancer, does not in itself need treatment. In this review, we challenge this view and explore the developments in the understanding of this controversial entity.
IgE‐induced histamine release from rat basophilic leukemia cell lines: isolation of releasing and nonreleasing clones (1981)

The rat basophilic leukemia (RBL) cell lines were cloned and the various sublines compared for their chromosome number, IgE-mediated histamine release and for IgE surface receptors. It was found that cell lines started from tumors at different times vary in both their chromosome number and their ability to release histamine by an IgE-mediated reaction. RBL-I and III have approximately 44 chromosomes and did not respond to an IgE-mediated reaction. RBL-II and RBL-IV have 68-73 chromosomes and showed moderate levels of histamine release (percent release mean = 5 +/- 2 and 10 +/- 4, respectively). The cloning of the RBL-IV line resulted in some sublines which were excellent histamine releasers (range 39-100%) and some which were relatively refractory (less than 10%) to IgE-mediated histamine release. These clones did not differ significantly in chromosome number. Recloning the releasing lines gave rise to poor releasers, whereas the recloning of poor releasers did not produce good releasers indicating that the mutational drift in culture is toward loss of histamine-releasing capacity. The number of IgE receptors and the rate of IgE association and dissociation were similar for the different cell lines. The study failed to disclose significant molecular weight differences in the IgE receptor from the various clones and sublines indicating that the failure to release probably does not reside in the receptor. The various cloned sublines are phenotypically stable, and the isolation of excellent histamine-releasing sublines are useful for studies of the complex phenomenon of the histamine release.
The Problem of Purifying Single‐Walled Carbon Nanotubes (2005)

In search of purity: As technologies requiring the use of carbon nanotubes become more refined, the purity of the nanotubes becomes an ever-increasingly important factor. This Highlight not only takes a look at some attempts to improve the purity of single-walled carbon nanotubes (SWNTs) but also puts forward some new procedures to enhance their purity (the image shows SWNTs before (left) and after (right) one of the procedures described).
Initial characterization of TREM-like transcript (TLT)–1: a putative inhibitory receptor within the TREM cluster (2002)

The TREMs (triggering receptors expressed on myeloid cells) represent a family of 5 receptors clustered on murine chromosome 17. TREMs 1 and 2 affect various aspects of myeloid cell activation and development, including responsiveness to lipopolysaccharide and regulation of dendritic cell maturation, yet no inhibitory receptor has been demonstrated within this cluster. Here we characterize TLT-1 (TREM-like transcript-1), a putative inhibitory receptor within the TREM cluster that contains an extracellular V-set Ig domain, a proline-rich region, and an immune receptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic tail. To our knowledge, TLT-1 is the first ITIM-containing receptor carrying a potential Src homology 3 domain ligand. TLT-1 transcripts are abundant in bone marrow cells, but not in lymphocytes, and phosphorylated TLT-1 associates with SHP-1, suggesting that it is indeed an inhibitory receptor. Based on these characteristics, it is likely that TLT-1 regulates the signaling of the TREM family receptors.
Zinc finger protein-dependent and -independent contributions to the in vivo off-target activity of zinc finger nucleases (2010)

Zinc finger nucleases (ZFNs) facilitate tailor-made genomic modifications in vivo through the creation of targeted double-stranded breaks. They have been employed to modify the genomes of plants and animals, and cell-based therapies utilizing ZFNs are undergoing clinical trials. However, many ZFNs display dose-dependent toxicity presumably due to the generation of undesired double-stranded breaks at off-target sites. To evaluate the parameters influencing the functional specificity of ZFNs, we compared the in vivo activity of ZFN variants targeting the zebrafish kdrl locus, which display both high on-target activity and dose-dependent toxicity. We evaluated their functional specificity by assessing lesion frequency at 141 potential off-target sites using Illumina sequencing. Only a minority of these off-target sites accumulated lesions, where the thermodynamics of zinc finger-DNA recognition appear to be a defining feature of active sites. Surprisingly, we observed that both the specificity of the incorporated zinc fingers and the choice of the engineered nuclease domain could independently influence the fidelity of these ZFNs. The results of this study have implications for the assessment of likely off-target sites within a genome and point to both zinc finger-dependent and -independent characteristics that can be tailored to create ZFNs with greater precision.
Cytotoxic activity of a recombinant fusion protein between interleukin 4 and Pseudomonas exotoxin. (1989)

A recombinant chimeric toxin in which the cell binding domain of Pseudomonas exotoxin (PE) was replaced by murine interleukin 4 (IL-4) was produced in Escherichia coli. This chimeric protein, IL-4-PE40, was cytotoxic to murine IL-4 receptor-bearing cell lines but had little effect on human cell lines lacking receptors capable of binding murine IL-4. A mutant form of IL-4-PE40 (termed IL-4-PE40 asp553) with very low ADP-ribosylating activity displayed mitogenic activity similar to that of IL-4 rather than cytotoxic activity. Because the cytotoxic effects of IL-4-PE40 were blocked by excess IL-4 or by neutralizing antibody to IL-4 (11B11), we conclude that the cytotoxic effect of IL-4-PE40 is specifically mediated through IL-4 receptors. IL-4-PE40 could be a useful reagent for specific elimination of cells bearing IL-4 receptors.
Comparison of Immunofluorescence Antibody Testing and Two Enzyme Immunoassays in the Serologic Diagnosis of Malaria (2007)

While the Newmarket EIA was a generally more specific assay, it was insufficiently sensitive relative to the IFA and the Cellabs EIA for screening purposes for malaria antibodies. The Cellabs EIA demonstrated the best overall sensitivity and is a reasonable choice as a serodiagnostic tool for malaria. It may also be useful as an adjunct to Giemsa-stained smear examination, to aid in cases of low parasitemia in previously nonimmune individuals.
Effect of oversampling in pixel arrays (1995)

In order to quantify the effect of oversampling in a pixel array, a new transfer function is defined. This transfer function is shown to provide a direct comparison between the practical performance of a pixel array with and without oversampling. It is also found to be useful for measuring the influence of different lattice structures on the array. Explicit formulas for the transfer function have also been derived for a few common types of pixel arrays. The same concepts and formulas also turned out to be useful in evaluating the performance of ordinary pixel arrays when the image is not bandlimited.
T Cell Receptor-MHC Class I Peptide Interactions: Affinity, Kinetics, and Specificity (1994)

The critical discriminatory event in the activation of T lymphocytes bearing αβ T cell receptors (TCRs) is their interaction with a molecular complex consisting of a peptide bound to a major histocompatibility complex (MHC)-encoded class I or class II molecule on the surface of an antigen-presenting cell. The kinetics of binding were measured of a purified TCR to molecular complexes of a purified soluble analog of the murine MHC class I molecule H-2L d (sH-2L d ) and a synthetic octamer peptide p2CL in a direct, real-time assay based on surface plasmon resonance. The kinetic dissociation rate of the MHC-peptide complex from the TCR was rapid (2.6 × 10 -2 second -1 , corresponding to a half-time for dissociation of approximately 27 seconds), and the kinetic association rate was 2.1 × 10 5 M -1 second -1 . The equilibrium constant for dissociation was approximately 10 -7 M. These values indicate that TCRs must interact with a multivalent array of MHC-peptide complexes to trigger T cell signaling.
The tyrosine corner: A feature of most greek key β‐barrel proteins (1994)

The Tyr corner is a conformation in which a tyrosine (residue "Y") near the beginning or end of an antiparallel beta-strand makes an H bond from its side-chain OH group to the backbone NH and/or CO of residue Y - 3, Y - 4, or Y - 5 in the nearby connection. The most common "classic" case is a delta 4 Tyr corner (more than 40 examples listed), in which the H bond is to residue Y - 4 and the Tyr chi 1 is near -60 degrees. Y - 2 is almost always a glycine, whose left-handed beta or very extended beta conformation helps the backbone curve around the Tyr ring. Residue Y - 3 is in polyproline II conformation (often Pro), and residue Y - 5 is usually a hydrophobic (often Leu) that packs next to the Tyr ring. The consensus sequence, then, is LxPGxY, where the first x (the H-bonding position) is hydrophilic. Residues Y and Y - 2 both form narrow pairs of beta-sheet H-bonds with the neighboring strand. delta 5 Tyr corners have a 1-residue insertion between the Gly and Tyr, forming a beta-bulge. One protein family has a delta 4 corner formed by a His rather than a Tyr, and several examples use Trp in place of Tyr. For almost all these cases, the protein or domain is a Greek key beta-barrel structure, the Tyr corner ends a Greek key connection, and it is well-conserved in related proteins. Most low-twist Greek key beta-barrels have 1 Tyr corner. "Reverse" delta 4 Tyr corners (H bonded to Y + 4) and other variants are described, all less common and less conserved. It seems likely that the more classic Tyr corners (delta 4, delta 5, and delta 3 Tyr, Trp, or His) contribute to the stability of a Greek key connection over a hairpin connection, and also that they may aid in the process of folding up Greek key structures.
The thioesterase domain from a nonribosomal peptide synthetase as a cyclization catalyst for integrin binding peptides (2002)

Nonribosomal peptide synthetases responsible for the production of macrocyclic compounds often use their C-terminal thioesterase (TE) domain for enzymatic cyclization of a linear precursor. The excised TE domain from the nonribosomal peptide synthetase responsible for the production of the cyclic decapeptide tyrocidine A, TycC TE, retains autonomous ability to catalyze head-to-tail macrocyclization of a linear peptide thioester with the native sequence of tyrocidine A and can additionally cyclize peptide analogs that incorporate limited alterations in the peptide sequence. Here we show that TycC TE can catalyze macrocyclization of peptide substrates that are dramatically different from the native tyrocidine linear precursor. Several peptide thioesters that retain a limited number of elements of the native peptide sequence are shown to be substrates for TycC TE. These peptides were designed to integrate an Arg-Gly-Asp sequence that confers potential activity in the inhibition of ligand binding by integrin receptors. Although enzymatic hydrolysis of the peptide thioester substrates is preferred over cyclization, TycC TE can be used on a preparative scale to generate both linear and cyclic peptide products for functional characterization. The products are shown to be inhibitors of ligand binding by integrin receptors, with cyclization and N(alpha)-methylation being important contributors to the nanomolar potency of the best inhibitors of fibrinogen binding to alpha IIb beta 3 integrin. This study provides evidence for TycC TE as a versatile macrocyclization catalyst and raises the prospect of using TE catalysis for the generation of diverse macrocyclic peptide libraries that can be probed for novel biological function.
Patterning the Vertebrate Neuraxis (1996)

Neuraxial patterning is a continuous process that extends over a protracted period of development. During gastrulation a crude anteroposterior pattern, detectable by molecular markers, is conferred on the neuroectoderm by signals from the endomesoderm that are largely inseparable from those of neural induction itself. This coarse-grained pattern is subsequently reinforced and refined by diverse, locally acting mechanisms. Segmentation and long-range signaling from organizing centers are prominent among the emerging principles governing regional pattern.
A subset of metastatic human colon cancers expresses elevated levels of transforming growth factor beta1. (1998)

Although transforming growth factor (TGF)-beta1 is a potent growth inhibitor of normal epithelial cells including colonocytes, TGF-beta1 has also been implicated as an enhancer of colon cancer metastasis. Decreasing TGF-beta1 protein levels in the metastatic U9 colon cancer cell line by antisense methodology decreased both U9 cell metastasis to the liver and s.c. tumor formation in a nude mouse system, and the tumors that did arise had regained TGF-beta1 expression (F. Huang et al, Cell Growth Differ., 6: 1635-1642, 1995). In addition, in a clinical immunohistochemistry study, colon cancers with elevated TGF-beta1 protein levels were found to be 18 times more likely to recur as distant metastases than colon cancers expressing low TGF-beta1 levels, after resection of the primary tumor (E. Friedman et al, Cancer Epidemiol. Biomark. Prev., 4:549-554, 1995). Because both studies implicated TGF-beta1 in colon cancer metastasis, we wished to know whether a selection bias for TGF-beta1 was maintained in metastatic cells or was only a property of the primary site tumors that were likely to metastasize. TGF-beta1 levels were measured using two different antibodies in paired primary site cancers and their metastases by immunohistochemistry and, in selected cases, by Western blot analysis. In 16 of 21 cases (76%) with antibody G and 23 of 31 cases (74%) with antibody P, higher expression of TGF-beta1 was found in colon cancer cells invading local lymph nodes compared with primary site colon cancer cells, or (2 and 6 cases, respectively) high TGF-beta1 expression in the primary site cancer was maintained in invasive cells. Analysis by Western blotting using both antibodies also demonstrated that higher levels of TGF-beta1 protein were found in metastases compared with the primary site tumor or normal tissue. Additional cases of paired primary site colon cancer, local lymph node metastases, and cancer cells metastasizing to distant sites were examined. In six of eight such cases (75%), TGF-beta1 levels were increased in both invasive cell populations compared with the primary site cancer (five cases), or high levels in the primary site cancer were maintained in the metastatic cells (one case). These data suggest that TGF-beta1 plays a role in promoting colon cancer metastasis throughout the metastatic process in roughly 75% of cases. TGF-beta1 may increase metastasis by paracrine mechanisms, such as suppression of local immune response or increased angiogenesis, as was seen with the U9 cell line. In those cancers with nonmutated TGF-beta receptors and nonmutated smad proteins like U9 cells, TGF-beta1 could also act in an autocrine manner to increase invasion by increasing cell motility (Hsu et al., Cell Growth Differ., 5: 267-275, 1994).
Encapsulation of the mosquito fungal pathogen Lagenidium giganteum (Oomycetes:Lagenidiales) in calcium alginate. (1987)

The asexual stages (presporangial mycelia) of Lagenidium giganteum cultured on sunflower seed extract were encapsulated in calcium alginate and remained infective to mosquito larvae, Culex quinquefasciatus, after storage at 15 degrees C for up to 75 days. Survival and zoospore release from the encapsulated mycelia persisted for up to 24 days after immersion in water. Encapsulated sexual stages (oospores), held at 23-26 degrees C for up to 35 days or frozen for 8-10 days, were infective to mosquito larvae for up to 48 days after immersion in water and during that time over 50% of the oospores germinated. In outdoor pools, encapsulated mycelia gave 100% control of Cx. quinquefasciatus at 6-7 days after treatment while encapsulated oospores gave 100% control at 11 days posttreatment.