gebhart/patrepeval huggingface dataset:
Thioredoxin reductase, a redox-active selenoprotein, is secreted by normal and neoplastic cells: presence in human plasma. (2000)

Thioredoxin (Trx) and Trx reductase (TrxR) are redox-active proteins that participate in multiple cellular events, including growth promotion, apoptosis, and cytoprotection. Studies on overexpression of Trx and TrxR in human cancers have indicated a role of these proteins in tumor development. In this study, we analyzed the expression of TrxR in peripheral blood cells, tumor-transformed leukemia, and melanoma cells and found, in addition to abundant plasma membrane localization, that TrxR was released from these cells. Secretory cells were observed at the single cell level using a sensitive enzyme-linked immunospot assay. The release was inducible, and physiological stimulation of human monocytes by IFN-gamma, lipopolysaccharide, and interleukin 1alpha significantly increased the number of TrxR-secreting cells (P = 0.004). Secretion of TrxR followed the classical Golgi pathway, and it was confirmed by metabolic labeling using [35S]methionine and [35S]cysteine. TrxR was also detected for the first time in fresh healthy blood donor plasma (n = 21; median concentration, 18.0 ng/ml), with biological activity as determined by insulin reduction assay. These results highlight the role of extracellular Trx and TrxR during inflammation and tumor progression. Released Trx, with its active site motif containing amino acids Cys-X-X-Cys, was recently shown to have chemoattractant properties beside its previously described antioxidant and cocytokine activities. Regeneration of oxidized Trx requires available TrxR outside the cell, the presence and induction of which is described in this paper for normal and transformed cells.
Hypertonic Saline Nasal Provocation Stimulates Nociceptive Nerves, Substance P Release, and Glandular Mucous Exocytosis in Normal Humans (1999)

Hypertonic saline (HTS) induces bronchoconstriction. Potential mechanisms were evaluated in a human nasal provocation model. Aliquots of normal saline (1 x NS, 100 microliters) and higher concentrations (3 x NS, 6 x NS, 12 x NS, 24 x NS) were sprayed into one nostril at 5-min intervals. Lavage fluids were collected from the ipsilateral and contralateral sides to determine the concentrations of specific mucus constituents. Nasal cavity air-space volume was assessed by acoustic rhinometry (AcRh). The distribution of substance-P-preferring neurokinin-1 (NK-1) receptor mRNA was assessed by in situ reverse transcriptase-polymerase chain reaction. Unilateral HTS induced unilateral dose-dependent increases in sensations of pain, blockage, and rhinorrhea, the weights of recovered lavage fluids, and concentrations of total protein, lactoferrin, mucoglycoprotein markers, and substance P. Contralateral, reflex-mediated effects were minor. There were no changes in IgG or AcRh measurements. NK-1 receptor mRNA was localized to submucosal glands. HTS caused pain with unilateral substance P release. The presumed nociceptive nerve efferent axon response led to glandular exocytosis, presumably through actions on submucosal gland NK-1 receptors. Vascular processes, including plasma exudation, filling of venous sinusoids, and mucosal edema were not induced in these normal subjects.
Tumor location and drug targeting using a monoclonal antibody (anti‐SSEA‐1) and antigen‐binding fragments (1986)

Both murine and heterotransplanted human nonseminomatous germ-cell tumors have been successfully located by external scintigraphy using radioiodinated anti-SSEA-1, a monoclonal IgM, and its pepsin-derived antigen-binding fragment, F(ab')2 mu. Antibody localization in the tumor is mainly due to antigenic specificity, rather than to nonspecific trapping, and depends strongly on the amount of time after injection. The antibody has been used for drug targeting in vitro and in vivo.
Synthesis and properties of fluorescent nucleotide substrates for DNA-dependent RNA polymerases. (1979)

A new class of fluorescent nucleotide analogs which contain the fluorophore 1-aminonaphthalene-5-sulfonate attached via a gamma-phosphoamidate bond has been synthesized. Both the purine and pyrimidine analogs have fluorescence emission maxima at 460 nm. Cleavage of the alpha-beta-phosphoryl bond produces change in both the absorption and fluorescence emission spectra. The fluorescence of the pyrimidine analogs is quenched; cleavage of the alpha-beta-phosphoryl bond of the UTP analog produces about a 14-fold increase in fluorescence intensity at 500 nm. Under the same conditions the fluorescence of the CTP analog increases about 8-fold, whereas the fluorescence of the purine analogs shows only a slight change. These derivatives are good substrates for Escherichia coli RNA polymerase with only slightly increased Km values and with Vmax values about 50 to 70% that of the normal nucleotides. They are used less efficiently by wheat germ RNA polymerase II. The ATP analog can be used by E. coli RNA polymerase to initiate RNA chains.
Optimising hot paths in a dynamic binary translator (2001)

In dynamic binary translation, code is translated "on the fly" at run-time, while the user perceives ordinary execution of the program on the target machine. Code fragments that are frequently executed follow the same sequence of flow control over a period of time. These fragments form a hot path and are optimised to improve the overall performance of the program.Multiple hot paths may also exist in programs. A program may choose to execute in one hot path for some time, but later switch to another hot path, or even cycle between hot paths. Hence, each hot path is able to capture the most frequent execution pattern for a particular run-time stage of the program. The end result is that scattered code is collected, merged and optimised in a special way.In this paper we describe the optimisations performed by UQDBT - a machine-adaptable dynamic binary translator. We provide an algorithm for finding hot paths using edge weight profiles, and we explain how to optimise code in a machine-independent way, based on hot path information.
Suppression of Hypersensitivity of Escherichia coli acrB Mutant to Organic Solvents by Integrational Activation of the acrEF Operon with the IS 1 or IS 2 Element (2001)

The AcrAB-TolC efflux pump plays an intrinsic role in resistance to hydrophobic solvents in Escherichia coli. E. coli OST5500 is hypersensitive to solvents due to inactivation of the acrB gene by insertion of IS30. Suppressor mutants showing high solvent resistance were isolated from OST5500. These mutants produced high levels of AcrE and AcrF proteins, which were not produced in OST5500, and in each mutant an insertion sequence (IS1 or IS2) was found integrated upstream of the acrEF operon, coding for the two proteins. The suppressor mutants lost solvent resistance on inactivation of the acrEF operon. The solvent hypersensitivity of OST5500 was suppressed by introduction of the acrEF operon with IS1 or IS2 integrated upstream but not by introduction of the operon lacking the integrated IS. It was concluded that IS integration activated acrEF, resulting in functional complementation of the acrB mutation. The acrB mutation was also complemented by a plasmid containing acrF or acrEF under the control of Plac. The wild-type tolC gene was found to be essential for complementation of the acrB mutation by acrEF. Thus, it is concluded that in these cells a combination of the proteins AcrA, AcrF, and TolC or the proteins AcrE, AcrF, and TolC is functional in solvent efflux instead of the AcrAB-TolC efflux pump.
DOS SIGLOS DE RELACIONES MÉXICO-EU, EN NOVEDOSA GUÍA DIGITAL (2007)

LA COPIOSA LITERATURA ACADEMICA VINCULADA CON LOS VARIADOS TEMAS DE LAS RELACIONES BILATERALES ENTRE MEXICO Y ESTADOS UNIDOS HA SIDO REUNIDA POR ESPECIALISTAS DEL INSTITUTO DE INVESTIGACIONES HISTORICAS, EN EL DISCO COMPACTO DOS SIGLOS DE RELACIONES MEXICO-ESTADOS UNIDOS. GUIA BIBLIOHEMEROGR FICA 1974-2005. SE TRATA DE UNA OBRA DIGITAL RESULTADO DEL ESFUERZO DE UN GRUPO DE ACADEMICOS Y JOVENES UNIVERSITARIOS, COORDINADOS POR MARCELA TERRAZAS, DE INVESTIGACIONES HISTORICAS, DONDE HAN SIDO COMPILADOS TRES MIL REGISTROS SOBRE TEXTOS, ARTICULOS, CAPITULOS EN LIBROS Y TESIS DOCTORALES, DE LA PLUMA DE AUTORES MEXICANOS Y ESTADUNIDENSES, PRINCIPALMENTE. LA LITERATURA CONTENIDA EN EL DISCO COMPACTO TRATA EL ESTUDIO DE LAS RELACIONES ENTRE AMBOS PAISES, LAS CUALES HAN SIDO HISTORICAMENTE TRASCENDENTES Y COMPLEJAS, ADEM S DE ADQUIRIR, DIA CON DIA, MAYOR IMPORTANCIA. CON ESTE NOVEDOSO MATERIAL, LOS ESTUDIOSOS DE LA TEM TICA TIENEN A SU ALCANCE LA POSIBILIDAD DE REVISAR EL CONOCIMIENTO GENERADO MEDIANTE INVESTIGACIONES DE RECIENTE FACTURA Y DE ALLANAR LAS DIFICULTADES QUE REPRESENTA LA DISPERSION DE CONTENIDOS. SU FORMATO PERMITE APROVECHAR LAS BONDADES DE LA TECNOLOGIA ELECTRONICA, DE MANERA QUE EL DISCO FACILITA LA BUSQUEDA DE CADA UNO DE ESTOS ASIENTOS, LOS CUALES CONTIENEN DATOS B SICOS EN TORNO A CADA PUBLICACION Y OTROS ELEMENTOS QUE COMPLEMENTAN LA REFERENCIA, TALES COMO UN BREVE RESUMEN DEL CONTENIDO EN INGLES Y EN ESPANOL, PALABRAS QUE LO DESCRIBEN Y LA FUENTE DONDE ES POSIBLE UBICARLO. DE ACUERDO CON MARCELA TERRAZAS, LA IDEA DE REALIZAR UNA GUIA DE MATERIALES BIBLIOHEMEROGR FICOS Y TESIS SOBRE LA RELACION ENTRE MEXICO Y ESTADOS UNIDOS DERIVO DE UN FIN M S AMBICIOSO: ESCRIBIR UNA HISTORIA GENERAL DE ESE VINCULO. PARA EFECTUAR ESTA OBRA DIGITAL SE REGISTRO LA LITERATURA SOBRE LOS VARIADOS TEMAS DEL LAZO BILATERAL, LA CUAL ES LA BASE PARA EL LIBRO SOBRE EL DEVENIR DE ESE NEXO, QUE APARECER  PROXIMAMENTE. DICHO CENSO COMPRENDE DEL PERIODO QUE VA DEL ESTABLECIMIENTO DE LAS RELACIONES DIPLOM TICAS ENTRE MEXICO Y LA UNION AMERICANA, EN 1822, HASTA FINALES DE 2005. ALICIA MAYER, TITULAR DE INVESTIGACIONES HISTORICAS, ASEVERO QUE SE TRATA DE UNA HERRAMIENTA DE GRAN UTILIDAD SOBRE EL VINCULO MEXICANO-ESTADUNIDENSE, ASUNTO CUYA COMPLEJIDAD Y TRASCENDENCIA NOS OBLIGA -CADA VEZ M S- A ESTUDIARLO RIGUROSAMENTE. CABE SENALAR QUE EL EQUIPO DE ESPECIALISTAS ENCARGADO DE COLABORAR EN ESTA TAREA ESTUVO INTEGRADO POR: CARMEN COLLADO Y ANA ROSA SU REZ ARGELLO, DEL INSTITUTO DE INVESTIGACIONES JOSE MARIA LUIS MORA; CRISTINA GONZ LEZ ORTIZ, DE LA FACULTAD DE ESTUDIOS SUPERIORES ACATL N; PATRICIA DE LOS RIOS, DE LA UNIVERSIDAD IBEROAMERICANA, Y PAOLO RIGUZZI, DE EL COLEGIO MEXIQUENSE.
Towards Accurate Free Energy Calculations in Ligand Protein-Binding Studies (2010)

Cells contain a multitude of different chemical reaction paths running simultaneously and quite independently next to each other. This amazing feat is enabled by molecular recognition, the ability of biomolecules to form stable and specific complexes with each other and with their substrates. A better understanding of this process, i.e. of the kinetics, structures and thermodynamic properties of biomolecule binding, would be invaluable in the study of biological systems. In addition, as the mode of action of many pharmaceuticals is based upon their inhibition or activation of biomolecule targets, predictive models of small molecule receptor binding are very helpful tools in rational drug design. Since the goal here is normally to design a new compound with a high inhibition strength, one of the most important thermodynamic properties is the binding free energy DeltaG(0). The prediction of binding constants has always been one of the major goals in the field of computational chemistry, because the ability to reliably assess a hypothetical compound's binding properties without having to synthesize it first would save a tremendous amount of work. The different approaches to this question range from fast and simple empirical descriptor methods to elaborate simulation protocols aimed at putting the computation of free energies onto a solid foundation of statistical thermodynamics. While the later methods are still not suited for the screenings of thousands of compounds that are routinely performed in computational drug design studies, they are increasingly put to use for the detailed study of protein ligand interactions. This review will focus on molecular mechanics force field based free energy calculations and their application to the study of protein ligand interactions. After a brief overview of other popular methods for the calculation of free energies, we will describe recent advances in methodology and a variety of exemplary studies of molecular dynamics simulation based free energy calculations.
Cloning of Higher Plant [omega]-3 Fatty Acid Desaturases (1993)

Arabidopsis thaliana T-DNA transformants were screened for mutations affecting seed fatty acid composition. A mutant line was found with reduced levels of linolenic acid (18:3) due to a T-DNA insertion. Genomic DNA flanking the T-DNA insertion was used to obtain an Arabidopsis cDNA that encodes a polypeptide identified as a microsomal omega-3 fatty acid desaturase by its complementation of the mutation. Analysis of lipid content in transgenic tissues demonstrated that this enzyme is limiting for 18:3 production in Arabidopsis seeds and carrot hairy roots. This cDNA was used to isolate a related Arabidopsis cDNA, whose mRNA is accumulated to a much higher level in leaf tissue relative to root tissue. This related cDNA encodes a protein that is a homolog of the microsomal desaturase but has an N-terminal extension deduced to be a transit peptide, and its gene maps to a position consistent with that of the Arabidopsis fad D locus, which controls plastid omega-3 desaturation. These Arabidopsis cDNAs were used as hybridization probes to isolate cDNAs encoding homologous proteins from developing seeds of soybean and rapeseed. The high degree of sequence similarity between these sequences suggests that the omega-3 desaturases use a common enzyme mechanism.
Multi-organ involvement and failure in selected accident cases with acute radiation syndrome observed at the Mayak Nuclear Facility (2005)

Mayak Production Association (Mayak PA) in the Southern Ural is the first Russian nuclear facility of plutonium production for weapons. Due to the lack of knowledge and experience in operating nuclear facilities, 19 radiation accidents including criticality accidents occurred and 59 individuals developed acute radiation syndrome (ARS) during commissioning and development of Mayak PA (1948–1958). Severe accidents that occurred at this facility are reviewed, and the initial symptoms and clinical courses of ARS in victims are discussed from the perspective of multi-organ involvement and failure.
Arsenic Sulfide Promotes Apoptosis in Retinoid Acid Resistant Human Acute Promyelocytic Leukemic NB4-R1 Cells through Downregulation of SET Protein (2014)

Tetra-arsenic tetra-sulfide (As4S4) is an arsenic compound with anti-tumor activity, especially in acute promyelocytic leukemia (APL) that are resistant to retinoic acid (RA). Although recent studies revealed that the therapeutic action of As4S4 is closely associated with the induction of cellular apoptosis, the exact molecular mechanism of action of As4S4 in RA-resistant APL remains to be clarified. In this study, we found that As4S4-induced apoptosis was accompanied by reduced mRNA and protein expression of SET gene in RA-resistant NB4-R1 cells. Moreover, RNAi knockdown of SET gene further promoted As4S4-induced apoptosis, while SET over-expression inhibited it, suggesting that As4S4 induces apoptosis through the reduction of SET protein in NB4-R1 cells. We also demonstrated that the knockdown of SET gene resulted in the upregulation of protein phosphatase 2 (PP2A) expression and the downregulation of promyelocytic leukemia and retinoic acid receptor α fusion gene (PML-RARα) expression, which were enhanced by As4S4 treatments. By contrast, over-expression of SET gene resulted in PP2A downregulation and PML-RARα upregulation, which were abolished by As4S4 pretreatment. Since PP2A is a pro-apoptotic factor and PMLRARα is an anti-apoptotic factor, our results suggest that As4S4-induced apoptosis in NB4-R1 cells is through the downregulation of SET protein expression, which in turn increases PP2A and reduces PML-RARα expressions to lead to cell apoptosis.
Heparinase inhibitsneovascularization. (1994)

Neovascularization is associated with the regulation of tissue development, wound healing, and tumor metastasis. A number of studies have focused on the role of heparin-like molecules in neovascularization; however, little is known about the role of heparin-degrading enzymes in neovascularization. We report here that the heparin-degrading enzymes, heparinases I and III, but not heparinase II, inhibited both neovascularization in vivo and proliferation of capillary endothelial cells mediated by basic fibroblast growth factor in vitro. We suggest that the role of heparinases in inhibition of neovascularization is through depletion of heparan sulfate receptors that are critical for growth factor-mediated endothelial cell proliferation and hence neovascularization. The differences in the effects of the three heparinases on neovascularization could be due to different substrate specificities for the enzymes, influencing the availability of specific heparin fragments that modulate heparin-binding cytokines involved in angiogenesis.
Analysis of multiple-source bipole-quadripole resistivity surveys using the apparent resistivity tensor (1986)

Abstract Measurements of apparent resistivity made using the bipole-dipole method depend upon the location and orientation of the current source relative to the body under study. Although it has been recognized that this dependence on orientation can be partially overcome by use of two current bipoles with different orientations, no agreement on the method of analysis of multiple source surveys has been reached. The most general form of presentation of such results is an apparent resistivity tensor. Various rotation invariants derived from the apparent resistivity tensor can be regarded as mean values of apparent resistivity, independent of the direction of the electric field, thus greatly reducing the "false anomalies" typical of single-source bipole- dipole survey results. Two of the tensor invariants obey the principle of reciprocity: if the roles of the current and potential electrodes are interchanged, the invariants are unchanged. The properties of the apparent resistivity tensor are demonstrated for selected simple models. For a horizontally layered medium, when the receiver array is far from the current source, the tensor is symmetric and has invariants which depend only on the distance from the current source. The extreme values of apparent resistivity occur when the electric field vector is tangential and radial relative to the current source. These extreme values correspond to the Schlumberger apparent resistivity and the "polar" dipole apparent resistivity, respectively.
Assessment of anti-amyloidogenic activity of marine red algaG. acerosaagainst Alzheimer’s beta-amyloid peptide 25–35 (2014)

Overall, the results suggest that G. acerosa might have direct interaction with the aggregated peptide, thereby preventing oligomerization and fibrillation of Aβ 25-35.
Shape complementarity at protein–protein interfaces (1994)

A matching algorithm using surface complementarity between receptor and ligand protein molecules is outlined. The molecular surfaces are represented by "critical points," describing holes and knobs. Holes (maxima of a shape function) are matched with knobs (minima). This simple and appealing surface representation has been previously described by Connolly [(1986) Biopolymers, Vol. 25, pp. 1229-1247]. However, attempts to implement this description in a docking scheme have been unsuccessful (e.g., Connolly, ibid.). In order to decrease the combinatorial complexity, and to make the execution time affordable, four critical hole/knob point matches were sought. This approach failed since some bound interfaces are relatively flat and do not possess four critical point matches. On the otherhand, matchings of fewer critical points require a very time-consuming, full conformational (grid) space search [Wang, (1991) Journal of Computational Chemistry, Vol. 12, pp. 746-750]. Here we show that despite the initial failure of this approach, with a simple and straightforward modification in the matching algorithm, this surface representation works well. Out of the 16 protein-protein complexes we have tried, 15 were successfully docked, including two immunoglobulins. The entire molecular surfaces were considered, with absolutely no additional information regarding the binding sites. The whole process is completely automated, with no manual intervention, either in the input atomic coordinate data, or in the matching. We have been able to reach this level of performance with the hole/knob surface description by using pairs of critical points along with their surface normals in the calculation of the transformation matrix. The success of this approach suggests that future docking methods should use geometric docking as the first screening filter.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of Actin Polymerization and Adhesion to Extracellular Matrix in Rac- and Rho-induced Cytoskeletal Reorganization (1997)

Most animal cells use a combination of actin-myosin-based contraction and actin polymerization- based protrusion to control their shape and motility. The small GTPase Rho triggers the formation of contractile stress fibers and focal adhesion complexes (Ridley, A.J., and A. Hall. 1992. Cell. 70:389-399) while a close relative, Rac, induces lamellipodial protrusions and focal complexes in the lamellipodium (Nobes, C.D., and A. Hall. 1995. Cell. 81:53-62; Ridley, A.J., H.F. Paterson, C.L. Johnston, D. Diekmann, and A. Hall. 1992. Cell. 70:401-410); the Rho family of small GTPases may thus play an important role in regulating cell movement. Here we explore the roles of actin polymerization and extracellular matrix in Rho- and Rac-stimulated cytoskeletal changes. To examine the underlying mechanisms through which these GTPases control F-actin assembly, fluorescently labeled monomeric actin, Cy3-actin, was introduced into serum-starved Swiss 3T3 fibroblasts. Incorporation of Cy3- actin into lamellipodial protrusions is concomitant with F-actin assembly after activation of Rac, but Cy3-actin is not incorporated into stress fibers formed immediately after Rho activation. We conclude that Rac induces rapid actin polymerization in ruffles near the plasma membrane, whereas Rho induces stress fiber assembly primarily by the bundling of actin filaments. Activation of Rho or Rac also leads to the formation of integrin adhesion complexes. Integrin clustering is not required for the Rho-induced assembly of actin-myosin filament bundles, or for vinculin association with actin bundles, but is required for stress fiber formation. Integrin-dependent focal complex assembly is not required for the Rac-induced formation of lamellipodia or membrane ruffles. It appears, therefore, that the assembly of large integrin complexes is not required for most of the actin reorganization or cell morphology changes induced by Rac or Rho activation in Swiss 3T3 fibroblasts.