gebhart/patrepeval huggingface dataset:
Exploring the charge space of protein–protein association: A proteomic study (2005)

The rate of association of a protein complex is a function of an intrinsic basal rate and of the magnitude of electrostatic steering. In the present study we analyze the contribution of electrostatics towards the association rate of proteins in a database of 68 transient hetero-protein-protein complexes. Our calculations are based on an upgraded version of the computer algorithm PARE, which was shown to successfully predict the impact of mutations on k(on) by calculating the difference in Columbic energy of interaction of a pair of proteins. HyPare (http://bip.weizmann.ac.il/HyPare), automatically calculates the impact of mutations on a per-residue basis for all residues of a protein-protein interaction, achieving a precision similar to that of PARE. Our calculations show that electrostatics play a marginal role (<10 fold) in determining the rate of association for about half of the complexes in the database. Strong electrostatic steering, which results in an increase of over 100-fold in k(on), was calculated for about 25% of the complexes. Applying HyPare to all 68 complexes in the database shows that a small number of residues are hotspots for association. About 40% of the hotspots are calculated to increase the rate of association upon mutation, and thus increase binding affinity. This is a much higher ratio than found for hotspots for dissociation, where the large majority cause weaker binding. About 40% of the hotspots are located outside the physical boundary of the binding site, making them ideal candidates for protein engineering. Our data shows that a majority of protein-protein complexes are not optimized for fast association. Hotspots are not evenly distributed between all types of amino acids. About 75% of all hotspots are of charged residues. This is understandable, as a charge-reverse mutant changes the total charge by 2. The small number of hydrophobic residues that are hotspots upon mutation probably relates to their location and surrounding. For 18 out of the 68 complexes in the database, experimental values of k(on) are available. For these, a basal rate of association was calculated to be in the range of 10(4)M(-1)s(-1) to 10(7)M(-1)s(-1). Some of these rates were verified independently from experimental mutant data. The basal rates were correlated with the size of the proteins and the shape of the interface.
Surfactants (2000)

Abstract The term surfactant is a contraction of surface‐active agent. Surfactant has become universally accepted to describe organic substances having certain characteristic features in structure and properties. The term detergent is often used interchangeably with surfactant. As a designation for a substance capable of cleaning, detergent can also encompass inorganic substances when these do in fact perform a cleaning function. More often, detergent refers to a combination of surfactants with other substances, organic or inorganic, formulated to enhance functional performance, specifically cleaning, over that of the surfactant alone. Surfactants are characterized by amphipathic structure, solubility, adsorption at interfaces, orientation at interfaces, micelle formation, and functional properties. Each is discussed, as are uses, production, and economic aspects.
Exosome and Microvesicle-Enriched Fractions Isolated from Mesenchymal Stem Cells by Gradient Separation Showed Different Molecular Signatures and Functions on Renal Tubular Epithelial Cells (2017)

Several studies have suggested that extracellular vesicles (EVs) released from mesenchymal stem cells (MSCs) may mediate MSC paracrine action on kidney regeneration. This activity has been, at least in part, ascribed to the transfer of proteins/transcription factors and different RNA species. Information on the RNA/protein content of different MSC EV subpopulations and the correlation with their biological activity is currently incomplete. The aim of this study was to evaluate the molecular composition and the functional properties on renal target cells of MSC EV sub-populations separated by gradient floatation. The results demonstrated heterogeneity in quantity and composition of MSC EVs. Two peaks of diameter were observed (90-110 and 170-190 nm). The distribution of exosomal markers and miRNAs evaluated in the twelve gradient fractions showed an enrichment in fractions with a flotation density of 1.08-1.14 g/mL. Based on this observation, we evaluated the biological activity on renal cell proliferation and apoptosis resistance of low (CF1), medium (CF2) and high (CF3) floatation density fractions. EVs derived from all fractions, were internalized by renal cells, CF1 and CF2 but not CF3 fraction stimulated significant cell proliferation. CF2 also inhibited apoptosis on renal tubular cells submitted to ischemia-reperfusion injury. Comparative miRNomic and proteomic profiles reveal a cluster of miRNAs and proteins common to all three fractions and an enrichment of selected molecules related to renal regeneration in CF2 fraction. In conclusion, the CF2 fraction enriched in exosomal markers was the most active on renal tubular cell proliferation and protection from apoptosis.
Dissociation of Second Messenger Activation by Parathyroid Hormone Fragments in Osteosarcoma Cells* (1991)

PTH activates multiple second messengers in its target cells, but the level at which the hormonal signal splits into different pathways is still unknown. To achieve insights on this issue, we have studied the structure-function relationship of PTH by analyzing the effects of bovine PTH-(1-34) [bPTH-(1-34)] and PTH fragments truncated at the N-terminus on the intracellular calcium concentration [( Ca2+]i) and cAMP production in the rat osteogenic sarcoma cell line UMR 106-01. [Ca2+]i was measured in single cells using fura-2. When exposed to 10(-7) M bPTH-(1-34), 20% of the cells responded with a transient increase in [Ca2+]i of variable amplitude. Equimolar doses of bPTH-(2-34), propionyl bPTH-(2-34) [(pbPTH-(2-34)], and bPTH-(3-34) also transiently increased [Ca2+]i, whereas both [tyrosine34]bPTH-(7-34) amide [bPTH-(7-34)] and bPTH-(30-34) were ineffective. The amplitude of the [Ca2+] i transients was dose-dependent, with threshold concentrations of 10(-10) M for bPTH-(1-34) and bPTH-(2-34), and 10(-9) M for bPTH-(3-34). The response rate to the active peptides ranged between 10-30%, without a clear dose-relatedness. A second addition of 10(-7) M bPTH-(1-34) to cells prestimulated with equimolar doses of bPTH-(2-34), pbPTH-(2-34), or bPTH-(3-34) produced another transient, whereas after exposure to 10(-7) M bPTH-(1-34), the cells were completely desensitized to a second homologous stimulation, suggesting that the binding affinity of the truncated peptides for the PTH receptor is lower than that of the intact bPTH-(1-34) fragment. In addition, both bPTH-(1-34) and bPTH-(2-34) dose-dependently stimulated cAMP production, but the former was more potent (ED50 = 10(-9) vs. 10(-7) M, respectively). On the contrary, pbPTH-(2-34), bPTH-(3-34), and bPTH-(7-34) had no effect on cAMP. Pretreating the cells with pertussis toxin to enhance cAMP responses via inhibition of Gi potentiated the effect of bPTH-(1-34) and bPTH-(2-34) and disclosed weak but detectable agonist action of pbPTH-(2-34). These results indicate that specific domains of the PTH molecule are linked to activation of different second messenger pathways; while the first two amino acids are indispensable for activating the cAMP system, generation of the [Ca2+]i signal appears to involve a longer domain, including the amino acid residue in position 3.
Requirement of Cell Cycle and Apoptosis Regulator 1 for Target Gene Activation by Wnt and β-Catenin and for Anchorage-independent Growth of Human Colon Carcinoma Cells (2009)

Aberrant Wnt signaling promotes oncogenesis by increasing cellular levels of beta-catenin, which associates with DNA-bound transcription factors and activates Wnt target genes. However, the molecular mechanism by which beta-catenin mediates gene expression is still poorly understood. Here, we show that cell cycle and apoptosis regulator 1 (CCAR1), which was recently shown to function as a transcriptional coactivator for nuclear receptors, also interacts with beta-catenin and enhances the ability of beta-catenin to activate expression of transiently transfected reporter genes. Furthermore, association of CCAR1 with the promoter of an endogenous Wnt/beta-catenin target gene in a colon cancer cell line depends on the presence of beta-catenin. Depletion of CCAR1 inhibits expression of several Wnt/beta-catenin target genes and suppresses anchorage-independent growth of the colon cancer cell line. Thus, CCAR1 is a novel component of Wnt/beta-catenin signaling that plays an important role in transcriptional regulation by beta-catenin and that, therefore, may represent a novel target for therapeutic intervention in cancers involving aberrantly activated Wnt/beta-catenin signaling.
Modeling of Tool-Tissue Interactions for Computer-Based Surgical Simulation: A Literature Review (2008)

Surgical simulators present a safe and potentially effective method for surgical training, and can also be used in robot-assisted surgery for pre- and intra-operative planning. Accurate modeling of the interaction between surgical instruments and organs has been recognized as a key requirement in the development of high-fidelity surgical simulators. Researchers have attempted to model tool-tissue interactions in a wide variety of ways, which can be broadly classified as (1) linear elasticity-based, (2) nonlinear (hyperelastic) elasticity-based finite element (FE) methods, and (3) other techniques that not based on FE methods or continuum mechanics. Realistic modeling of organ deformation requires populating the model with real tissue data (which are difficult to acquire in vivo) and simulating organ response in real time (which is computationally expensive). Further, it is challenging to account for connective tissue supporting the organ, friction, and topological changes resulting from tool-tissue interactions during invasive surgical procedures. Overcoming such obstacles will not only help us to model tool-tissue interactions in real time, but also enable realistic force feedback to the user during surgical simulation. This review paper classifies the existing research on tool-tissue interactions for surgical simulators specifically based on the modeling techniques employed and the kind of surgical operation being simulated, in order to inform and motivate future research on improved tool-tissue interaction models.
Potentiation of diacylglycerol‐induced activation of protein kinase C by lysophospholipids (1993)

Lysophospholipid, particularly 2-lysophosphatidylcholine (lysoPtdCho), significantly potentiates the diacylglycerol (DAG)-induced activation of protein kinase C (PKC) in vitro. LysoPtdCho shows no effect, unless DAG and phosphatidylserine (PtdSer) are present. This lysoPtdCho action also depends on its own as well as on Ca2+ concentration. At physiological Ca2+ concentrations, the activation of the alpha-, beta-, and gamma-subspecies (cPKC) is enhanced by lysoPtdCho in the 10(-6) M range, but inversely inhibited in the 10(-5) M range. The delta- and epsilon-subspecies (nPKC), which are enzymatically insensitive to Ca2+, are mostly inhibited by lysoPtdCho at its low concentrations. The enhancement of cPKC activation by lysoPtdCho is due to the increase in an apparent affinity of the enzyme for PtdSer but not for DAG. The results may account, at least in part, for the previous observations made with intact cell systems that lysoPtdCho significantly potentiates the DAG-induced cellular responses such as T-lymphocyte activation and HL-60 cell differentiation [(1992) Trends Biochem. Sci. 17, 414-417].
Reflectance analysis based countermeasure technique to detect face mask attacks (2013)

Face photographs, videos or masks can be used to spoof face recognition systems. Recent studies show that face recognition systems are vulnerable to these attacks. In this paper, a countermeasure technique, which analyzes the reflectance characteristics of masks and real faces, is proposed to detect mask attacks. There are limited studies on countermeasures against mask attacks. The reason for this delay is mainly due to the unavailability of public mask attack databases. In this study, a 2D+3D face mask attack database is used which is prepared for a research project in which the authors are all involved. The performance of the countermeasure is evaluated using the texture images which were captured during the acquisition of 3D scans. The results of the proposed countermeasure outperform the results of existing techniques, achieving a classification accuracy of 94.47%. In this paper, it is also proved that reflectance analysis may provide more information for the purpose of mask spoofing detection compared to texture analysis.
THE PATHWAY OF EUKARYOTIC mRNA FORMATION (1983)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Specific inhibition of transcription by triple helix-forming oligonucleotides. (1992)

Homopyrimidine oligonucleotides bind to the major groove of a complementary homopyrimidine.homopurine stretch by triple helix formation. The bla gene from transposon Tn3 contains a homopyrimidine.homopurine sequence of 13 base pairs located just downstream of the RNA polymerase binding site. A 13-mer homopyrimidine oligonucleotide targeted to this sequence was tested for its effect on transcription of the bla gene in vitro. We show that the consequence of triple helix formation in front of the Escherichia coli RNA polymerase-promoter complex is to block the holoenzyme at its start site during a period that is dependent on temperature. The temperature dependence of transcription inhibition shows a direct correlation between this effect and the stabilization of the triple helix. Substitution of 5-methylcytosine to cytosine in the 13-mer oligonucleotide enhances triplex stability and transcription inhibition. Transcription inhibition by this synthetic repressor was also confirmed by footprinting studies demonstrating its specificity of action. The 13-mer oligonucleotide containing a psoralen derivative covalently linked to its 5' end shows an irreversible and specific inhibition of transcription initiation after exposure to light of wavelength greater than 310 nm.
Purification and identification of tyrosine‐phosphorylated proteins from B lymphocytes stimulated through the antigen receptor (1994)

The activation of protein tyrosine kinase (PTKs) and subsequent tyrosine phosphorylation of cellular proteins is a critical initial signal in the response of eukaryotic cells to mitogens, differentiative signals, and other stimuli. A number of PTK substrates have been identified and many of these are components of signal transduction pathways that regulate cell function. However, the majority of proteins that are tyrosine-phosphorylated in response to receptor signaling remain unidentified. As some of these unidentified PTK substrates may also be signal-transducing proteins, their identification and functional characterization is an important objective towards understanding receptor signaling. We describe the development of a comprehensive and general process for the isolation and structural characterization of tyrosine-phosphorylated proteins. The method involves enrichment by anti-phosphotyrosine affinity chromatography, electrophoretic concentration and separation, and proteolytic fragmentation of individual purified phosphoproteins. Resulting peptide fragments are separated by microbore reverse-phase high performance liquid chromatography (RP-HPLC) and a portion of the eluted peptides are subjected to electrospray-mass spectrometry (ES/MS) for accurate determination of peptide masses. Proteolytic fragmentation of a protein produces a characteristic set of peptide masses that can be used to rapidly identify the protein by searching databases containing the peptide mass "fingerprints" for all known proteins. The identity of the protein established by this method can be confirmed by sequence analysis of selected peptides. We have applied this procedure to the analysis of PTK substrates from B lymphocytes that have been stimulated through the B cell antigen receptor (BCR). Signaling by this receptor is involved in the generation of antibodies against foreign molecules (antigens). The BCR activates multiple PTKs which phosphorylate at least 30 different proteins. We have identified several of these tyrosine-phosphorylated proteins, including Syk, a PTK that is known to be tyrosine-phosphorylated in activated B cells. Thus, the procedure described here can be used to identify regulatory proteins of low abundance. The process consists of a logical succession of compatible steps that avoids pitfalls inherent to prior attempts to characterize low abundance phosphoproteins and should find wide use for the identification of tyrosine-phosphorylated proteins in other cell types.
A Point Mutation (D79N) of the α2A Adrenergic Receptor Abolishes the Antiepileptogenic Action of Endogenous Norepinephrine (1998)

Norepinephrine serves as a neurotransmitter for a population of neurons the cell bodies of which reside in a brainstem nucleus and the axons of which project widely to discrete subsets of forebrain neurons. Norepinephrine powerfully inhibits epileptogenesis in the kindling model. Pharmacological methods have demonstrated that the antiepileptogenic actions of norepinephrine are exerted via alpha2 adrenergic receptors residing on targets of noradrenergic neurons. The existence of three alpha2 adrenergic receptor subtypes together with the lack of subtype-specific ligands has precluded understanding the role of individual alpha2 adrenergic receptor subtypes in the antiepileptogenic actions of norepinephrine. Gene targeting was used to introduce a point mutation into the alpha2A adrenergic subtype in the mouse genome. The mutation produced a marked enhancement of epileptogenesis and abolished the proepileptogenic actions of the alpha2 adrenergic receptor antagonist idazoxan. These studies reveal the crucial contribution of the alpha2A receptor subtype in suppression of epileptogenesis. Development of agents that promote selective activation of the alpha2A receptor subtype may provide novel therapeutic strategies for the prophylaxis of epilepsy.
Cell surface expression of the C3b/C4b receptor (CR1) protects Chinese hamster ovary cells from lysis by human complement. (1992)

The C3b/C4b receptor, also known as complement receptor type 1 (CR1, CD35), is a single chain glycoprotein consisting of 30 repeating homologous protein domains known as short consensus repeats (SCR) followed by transmembrane and cytoplasmic domains. A series of recombinant proteins derived from CR1 has been prepared and assessed for the capacity to inhibit complement lysis of the host Chinese hamster ovary (CHO) cells. The full-length recombinant CR1 inhibited human complement-mediated CHO cell lysis, and the efficiency of inhibition was directly proportional to the number of receptors/cell. The SCR 15-18 of CR1, but not SCR 15-16, inhibited complement lysis of the host CHO cell, bound monomeric C3b (Kd,app = 6.5 x 10(-7) M), and dimeric C3b (Kd = 1.8 x 10(-8) M), and served as a cofactor in the proteolysis of C3b by factor I, confirming and extending the observations of Fearon and colleagues (Kalli, K. R., Hsu, P., Bartow, T. J., Ahearn, J. M., Matsumoto, A. K., Klickstein, L. B., and Fearon, D. T. (1991) J. Exp. Med. 174, 1451-1460). The SCR 1-4 of CR1, but not SCR 1-2, also inhibited complement lysis of the host CHO cell, indicating that more than two SCR are necessary and that four SCR are sufficient for optimal C4b binding to CR1. Thus, the structural requirements for C4b binding are analogous to those for C3b binding, namely, four SCR of CR1 form the binding sites for each of these proteins. CR1 has long been recognized to regulate extrinsic complement activation, that is, to bind to and promote the degradation of fluid phase C3b and of C3b attached to immune complex. These results demonstrate that CR1 is also an intrinsic regulator of complement activation in that, under appropriate conditions, CR1 inhibits complement-mediated lysis of the cell on which it is expressed.
Building and Using a Fault-Tolerant MPI Implementation (2004)

In this paper we discuss the design and use of a fault-tolerant MPI (FT-MPI) that handles process failures in a way beyond that of the original MPI static process model. FTMPI allows the semantics and associated modes of failures to be explicitly controlled by an application via a modified functionality within the standard MPI 1.2 API. Given is an overview of the FT-MPI semantics, architecture design, example usage and sample applications. A short discussion is given on the consequences of designing a fault-tolerant MPI both in terms of how such an implementation handles failures at multiple levels internally as well as how existing applications can use new features while still remaining within the MPI standard.
Identification of immunostimulatory dendritic cells in the synovial effusions of patients with rheumatoid arthritis. (1985)

Dendritic cells in the circulation are leukocytes that are rich in Ia antigens and that actively stimulate T cell replication. We have identified dendritic cells in the joint effusions of patients with rheumatoid arthritis. By phase-contrast and immunofluorescence microscopy, synovial mononuclear cells contained 1-5% dendritic profiles that were rich in HLA-DR and DQ, had small amounts of C3bi receptor, and lacked a battery of monocyte and lymphocyte markers. These dendritic cells could be enriched to 60-80% purity by cytolytic depletion of monocytes and lymphocytes with a group of monoclonal antibodies (MAb) and complement. By transmission electron microscopy, the dendritic cell processes were bulbous in shape and lacked organelles. The cytoplasm had few lysosomes or endocytic vacuoles but contained a well-developed smooth reticulum that was comparable to that previously described in the Ia-rich interdigitating cells of lymphoid tissues. The growth of sodium periodate-modified T lymphocytes was used as a rapid quantitative assay of accessory cell function. Synovial mononuclear cells were some ten times more active than normal blood cells. Treatment with alpha-Ia MAb and complement ablated stimulatory function. In contrast, removal of monocytes (MAb, 3C10) or monocytes and B (MAb, BA-1) plus T (MAb, OKT3, or T101) lymphocytes did not significantly alter total activity, and the function per viable cell increased four- to eightfold. We conclude that rheumatoid arthritis synovial fluids contain cells that are comparable in function, phenotype, and structure to blood dendritic cells, although the frequency (1-5%) is 10 times greater in joints. The reason for their accumulation in the articular cavity is not known, but dendritic cells may be important in perpetuating the joint inflammation characteristic of this disease.