gebhart/patrepeval huggingface dataset:
T cell recognition of transforming proteins encoded by mutated ras proto-oncogenes (1991)

Activated ras proto-oncogenes contribute to the pathogenesis of many animal and human malignancies. ras proto-oncogenes are generally activated by point mutations within codons 12 or 61, which result in the expression of ras protein (p21) bearing characteristic single amino acid substitutions at the corresponding residues. The purpose of the current study was to determine whether the presence of single transforming amino acid substitutions can render normal ras protein immunogenic and, thus, a possible target for T cell-mediated tumor therapy. In initial experiments, C57BL/6 mice were immunized with a synthetic peptide corresponding to residues 5 through 16 of p21 containing the transforming substitution of arginine for normal glycine at residue 12. The results demonstrated that class II MHC-restricted T cells which were specific for the peptide could be elicited, and that the peptide-induced T cells could specifically recognize the corresponding intact p21 ras protein. Recognition of p21 ras protein by peptide-specific T cells implies that C57BL/6 APC can process the activated ras protein in a fashion that allows presentation of digested protein by class II MHC molecules in a configuration similar to the configuration with synthetic peptide. Evaluation of the immunogenicity of peptides containing alternative transforming amino acid substitutions of ras protein demonstrated that some, but not all, were immunogenic in individual strains of mice. Therefore, although ras protein-specific T cells can be elicited by immunization with synthetic peptides, not all of the potential ras mutations commonly associated with malignancy may be recognizable by T cells from all individuals.
Potatoes (1993)

A historical account of the role of the potato in scurvy prevention and cure underlines the nutritional virtues of this vegetable.
Effects of zidovudine-selected human immunodeficiency virus type 1 reverse transcriptase amino acid substitutions on processive DNA synthesis and viral replication (1996)

Certain amino acid substitutions in the reverse transcriptase (RT), including D67N, K70R, T215Y, and K219Q, cause high-level resistance of human immunodeficiency virus type 1 (HIV-1) to zidovudine (3'-azidothymidine; AZT) and appear to approximate the template strand of the enzyme-template-primer complex in structural models. We studied whether this set of mutations altered RT-template-primer interaction as well as their effect on virus replication in the absence of inhibitor. When in vitro polymerization was limited to a single association of an RT with an oligodeoxynucleotide-primed heteropolymeric RNA template (a single processive cycle), recombinant-expressed mutant 67/70/215/219 RT synthesized 5- to 10-fold more high-molecular-weight DNA products (>200 nucleotides in length) than wild-type RT. This advantage was maintained as deoxynucleoside triphosphate (dNTP) concentrations were decreased to limiting levels. In contrast, no difference was seen between wild-type and mutant RTs under conditions allowing repeated associations of enzyme with template-primer. Because intracellular dNTP concentrations are low prior to mitogenic stimulation, we compared replication of mutant 67/70/215/219 virus and wild-type virus in peripheral blood mononuclear cells (PBMC) stimulated before and after infection. In the absence of inhibitor, mutant 67/70/215/219 virus had a replication advantage in PBMC stimulated with phytohemagglutinin and interleukin-2 after infection, but virus replication was similar in PBMC stimulated before infection in vitro. The results confirm that RT mutations D67N, K70R, T215Y, and K219Q affect an enzyme-template-primer interaction in vitro and suggest that such substitutions may affect HIV-1 pathogenesis during therapy by increasing viral replication capacity in cells stimulated after infection.
In situ Phosphorylation of Platelet Actin-binding Protein by cAMP-dependent Protein Kinase Stabilizes It against Proteolysis by Calpain (1989)

To identify the protein kinase that is responsible for catalyzing phosphorylation of actin-binding protein (ABP) in platelets, we have examined the effects of protein kinase C and cAMP-dependent protein kinase on this process. We found that purified platelet protein kinase C from platelets was unable to phosphorylate ABP in vitro. However, a crude platelet kinase preparation phosphorylated ABP in the presence of cAMP, but not in the presence of Ca2+/phosphatidylserine. Fresh platelet plasma membranes incubated with [gamma-32P]ATP phosphorylated ABP in the presence of cAMP and the process was blocked by a cAMP-dependent protein kinase inhibitor; ABP phosphorylation induced by prostaglandin E1 (PGE1) appeared to be reduced by the subsequent addition of thrombin. These results strongly suggest that in situ ABP is phosphorylated by activated cAMP-dependent protein kinase when platelet function is inhibited by PGE1. Furthermore, in the PGE1-treated platelets, ABP was proteolyzed at a slower rate than in control platelets when they were lysed with Triton in the absence of EGTA. Partially purified ABP was proteolyzed by calpain in vitro at a slower rate as well. It was demonstrated that ABP from PGE1-treated platelets recovered its sensitivity to calpain after ABP was incubated with a protein phosphatase that had been purified from platelets. We postulate that ABP is stabilized against proteolysis in response to cAMP-elevating agents and that this blocks cytoskeleton reorganization.
Expression of anti-VEGF antibody together with anti-EGFR or anti-FAP enhances tumor regression as a result of vaccinia virotherapy (2015)

The tumor microenvironment plays an important role in tumor growth and progression. Here we demonstrate that vaccinia virus-mediated, constitutively expressed intratumoral antibodies against vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), and fibroblast activation protein (FAP) significantly improved tumor regression and oncolytic virotherapy through suppression of angiogenesis, cell proliferation, and stromagenesis in virus-colonized tumors. In contrast to the tumor growth inhibition by the three tumor growth-inhibiting antibodies individually, when two of the three antibodies were expressed simultaneously by single vaccinia virus strains tumor regression was further enhanced. These findings strongly indicate that interference with the two tumor growth-stimulating mechanisms did in fact result in enhanced therapeutic efficacy in tumor xenograft models and may lead to an effective therapy in patients with cancer.
Pyruvate production and excretion by the luminous marine bacteria (1977)

During aerobic growth on glucose, several species of luminous marine bacteria exhibited an imcomplete oxidative catabolism of substrate. Pyruvate, one of the products of glucose metabolism, was excreted into the medium during exponential growth and accounted for up to 50% of the substrate carbon metabolized. When glucose was depleted from the medium, the excreted pyruvate was promptly utilized, demonstrating that the cells are capable of pyruvate catabolism. Pyruvate excretion is not a general phenomenon of carbohydrate metabolism since it does not occur during the utilization of glycerol or maltose. When cells pregrown on glycerol were exposed to glucose, they began to excrete pyruvate, even if protein synthesis was blocked with chloramphenicol. Glucose thus appears to have an effect on the activity of preexisting catabolic enzymes.
From Spectrum Pooling to Space Pooling: Opportunistic Interference Alignment in MIMO Cognitive Networks (2010)

We describe a noncooperative interference alignment (IA) technique which allows an opportunistic multiple input multiple output (MIMO) link (secondary) to harmlessly coexist with another MIMO link (primary) in the same frequency band. Assuming perfect channel knowledge at the primary receiver and transmitter, capacity is achieved by transmiting along the spatial directions (SD) associated with the singular values of its channel matrix using a water-filling power allocation (PA) scheme. Often, power limitations lead the primary transmitter to leave some of its SD unused. Here, it is shown that the opportunistic link can transmit its own data if it is possible to align the interference produced on the primary link with such unused SDs. We provide both a processing scheme to perform IA and a PA scheme which maximizes the transmission rate of the opportunistic link. The asymptotes of the achievable transmission rates of the opportunistic link are obtained in the regime of large numbers of antennas. Using this result, it is demonstrated that depending on the signal-to-noise ratio and the number of transmit and receive antennas of the primary and opportunistic links, both systems can achieve transmission rates of the same order.
Towards in situ tissue repair: Human mesenchymal stem cells express chemokine receptors CXCR1, CXCR2 and CCR2, and migrate upon stimulation with CXCL8 but not CCL2 (2007)

The recruitment of bone marrow CD34- mesenchymal stem- and progenitor cells (MSC) and their subsequent differentiation into distinct tissues is the precondition for in situ tissue engineering. The objective of this study was to determine the entire chemokine receptor expression profile of human MSC and to investigate their chemotactic response to the selected chemokines CCL2, CXCL8 and CXCL12. Human MSC were isolated from iliac crest bone marrow aspirates and showed a homogeneous population presenting a typical MSC-related cell surface antigen profile (CD14-, CD34-, CD44+, CD45-, CD166+, SH-2+). The expression profile of all 18 chemokine receptors was determined by real-time PCR and immunohistochemistry. Both methods consistently demonstrated that MSC express CC, CXC, C and CX(3)C receptors. Gene expression and immunohistochemical analysis documented that MSC express chemokine receptors CCR2, CCR8, CXCR1, CXCR2 and CXCR3. A dose-dependent chemotactic activity of CXCR4 and CXCR1/CXCR2 ligands CXCL12 and CXCL8 (interleukin-8) was demonstrated using a 96-well chemotaxis assay. In contrast, the CCR2 ligand CCL2 (monocyte chemoattractant protein-1, MCP-1) did not recruited human MSC. In conclusion, we report that the chemokine receptor expression profile of human MSC is much broader than known before. Furthermore, for the first time, we demonstrate that human MSC migrate upon stimulation with CXCL8 but not CCL2. In combination with already known data on MSC recruitment and differentiation these are promising results towards in situ regenerative medicine approaches based on guiding of MSC to sites of degenerated tissues.
Fiber optic digital video signals transport for broadband subscriber network (2003)

A discussion is presented of various approaches for the fiber-based broadband integrated services digital network. Emphasis is placed on residential area use, focusing on service aspects, system architecture, and transmission technology from the viewpoint of video signal transport. Two methods used to realize broadband subscriber networks are described in detail.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Purification and properties of an intracellular leucine aminopeptidase from the fungus,Penicillium citrinum strain IFO 6352 (1996)

An intracellular leucine aminopeptidase (LAP) fromPenicillium citrinum (IFO 6352) was purified to homogeneity using three successive purification steps. The enzyme has a native molecular mass of 63 kDa using HPLC gel filtration analysis and a molecular mass of 65 kDa when using SDS-polyacrylamide gel electrophoresis. This monomeric aminopeptidase showed maximum enzyme activity at pH 8.5. An optimum temperature was 45–50°C whenl-Leu-p-nitroanilide (pNA) was the substrate, and enzyme activity drastically decreased above 60°C. The Michaelis-Menten constants forl-Leu-pNA andl-Met-pNA were 2.7 mM and 1.8 mM, respectively. When the enzyme reacted with biosynthetic methionyl human growth hormone, it showed high specificity for N-terminal methionine residue and recognized a stop sequence (Xaa-Pro). The aminopeptidase was inactivated by EDTA or 1,10-phenanthroline, indicating that it is a metallo-exoprotease. Enzyme activity was restored to 90% of maximal activity by addition of Co2+ ions. The activity of EDTA-treated enzyme was restored by addition of Zn2+, but reconstitution with Ca2+, Mg2+ or Mn2+ restored some enzyme activity. It is likely that Co2+ ions play an important role in the catalysis or stability of thePenicillium citrinum aminopeptidase, as zinc plays a similar function in other leucine aminopeptidases.
Overproduction of the pyruvate dehydrogenase multienzyme complex of Escherichia coli and site-directed substitutions in the E1p and E2p subunits (1992)

The aceEF-lpd operon of Escherichia coli encodes the pyruvate dehydrogenase (E1p), dihydrolipoamide acetyltransferase (E2p) and dihydrolipoamide dehydrogenase (E3) subunits of the pyruvate dehydrogenase multienzyme complex (PDH complex). An isopropyl beta-D-thiogalactopyranoside-inducible expression system was developed for amplifying fully lipoylated wild-type and mutant PDH complexes to over 30% of soluble protein. The extent of lipoylation was related to the degree of aeration during amplification. The specific activities of the isolated PDH complexes and the E1p component were 50-75% of the values normally observed for the unamplified complex. This could be due to altered stoichiometries of the overproduced complexes (higher E3 and lower E1p contents) or inactivation of E1p. The chaperonin, GroEL, was identified as a contaminant which copurifies with the complex. Site-directed substitutions of an invariant glycine residue (G231A, G231S and G231M) in the putative thiamine pyrophosphate-binding fold of the E1p component had no effect on the production of high-molecular-mass PDH complexes but their E1p and PDH complex activities were very low or undetectable, indicating that G231 is essential for the structural or catalytic integrity of E1p. A minor correction to the nucleotide sequence, which leads to the insertion of an isoleucine residue immediately after residue 273, was made. Substitution of the conserved histidine and arginine residues (H602 and R603) in the putative active-site motif of the E2p subunit confirmed that H602 of the E. coli E2p is essential, whereas R603 could be replaced without inactivating E2p. Deletions affecting putative secondary structural elements at the boundary of the E2p catalytic domain inhibited catalytic activity without affecting the assembly of the E2p core or its ability to bind E1p, indicating that the latter functions are determined elsewhere in the domain. The results further consolidate the view that chloramphenicol acetyltransferase serves as a useful structural and functional model for the catalytic domain of the lipoate acyltransferases.
Buildup Mechanism for Poly(l-lysine)/Hyaluronic Acid Films onto a Solid Surface (2001)

The formation of a new kind of biocompatible film based on poly(l-lysine) and hyaluronic acid (PLL/HA) by alternate deposition of PLL and HA was investigated. Optical waveguide lightmode spectroscopy, streaming potential measurements, atomic force microscopy, and quartz crystal microbalance (QCM) were used to analyze the different aspects of the buildup process such as the deposited mass after each new polyelectrolyte adsorption, the overall surface charge of the film, and its morphology. As for “conventional” polyelectrolyte multilayer systems, the driving force of the buildup process is the alternate overcompensation of the surface charge after each PLL and HA deposition. The construction of (PLL/HA)n films takes place over two buildup regimes. The first one is characterized by the formation of isolated islands that grow both by addition of new polyelectrolytes on their top and by mutual coalescence of the islands. The second regime sets in once a continuous film is formed after the eighth layer pair deposition in our working conditions and is characterized by an exponential increase of the mass. QCM measurements at different frequencies evidenced a viscoelastic behavior of the films with a shear viscosity on the order of 0.1 Pa·s. This new kind of biocompatible film incorporating a natural polymer of the cartilage and a widely used polypeptide is of potential use for cell-targeted action.
Partial-volume Bayesian classification of material mixtures in MR volume data using voxel histograms (1998)

We present a new algorithm for identifying the distribution of different material types in volumetric datasets such as those produced with magnetic resonance imaging (MRI) or computed tomography (CT). Because we allow for mixtures of materials and treat voxels as regions, our technique reduces errors that other classification techniques can create along boundaries between materials and is particularly useful for creating accurate geometric models and renderings from volume data. It also has the potential to make volume measurements more accurately and classifies noisy, low-resolution data well. There are two unusual aspects to our approach. First, we assume that, due to partial-volume effects, or blurring, voxels can contain more than one material, e.g., both muscle and fat; we compute the relative proportion of each material in the voxels. Second, we incorporate information from neighboring voxels into the classification process by reconstructing a continuous function, rho(x), from the samples and then looking at the distribution of values that rho(x) takes on within the region of a voxel. This distribution of values is represented by a histogram taken over the region of the voxel; the mixture of materials that those values measure is identified within the voxel using a probabilistic Bayesian approach that matches the histogram by finding the mixture of materials within each voxel most likely to have created the histogram. The size of regions that we classify is chosen to match the spacing of the samples because the spacing is intrinsically related to the minimum feature size that the reconstructed continuous function can represent.
Analysis of Minimum Distances in High-Dimensional Musical Spaces (2008)

We propose an automatic method for measuring content-based music similarity, enhancing the current generation of music search engines and recommended systems. Many previous approaches to track similarity require brute-force, pair-wise processing between all audio features in a database and therefore are not practical for large collections. However, in an Internet-connected world, where users have access to millions of musical tracks, efficiency is crucial. Our approach uses features extracted from unlabeled audio data and near-neigbor retrieval using a distance threshold, determined by analysis, to solve a range of retrieval tasks. The tasks require temporal features-analogous to the technique of shingling used for text retrieval. To measure similarity, we count pairs of audio shingles, between a query and target track, that are below a distance threshold. The distribution of between-shingle distances is different for each database; therefore, we present an analysis of the distribution of minimum distances between shingles and a method for estimating a distance threshold for optimal retrieval performance. The method is compatible with locality-sensitive hashing (LSH)-allowing implementation with retrieval times several orders of magnitude faster than those using exhaustive distance computations. We evaluate the performance of our proposed method on three contrasting music similarity tasks: retrieval of mis-attributed recordings (fingerprint), retrieval of the same work performed by different artists (cover songs), and retrieval of edited and sampled versions of a query track by remix artists (remixes). Our method achieves near-perfect performance in the first two tasks and 75% precision at 70% recall in the third task. Each task was performed on a test database comprising 4.5 million audio shingles.
Alternative syntheses of steroidal maleimides (1983)

The described synthesis starts from the α-keto esters VIII and XVI which afford the maleimides X and XVIII via products of condensation with carbamoylmethylenetriphenylphosphorane ( IX and XVII ). In this way, the steroidal maleimides X and XVIII (structurally similar to the cardenolides), derived from 17β-androstanyl-(2-maleimide) and 21-nor-pregnanyl-(2-maleimide) were prepared. Other routes for their preparation have been studied.
Vascular biology of eicosanoids and atherogenesis (2009)

Atherosclerosis is a chronic and progressive inflammatory vascular disease that is characterized by a complex interplay between some components of the bloodstream and the arterial wall. The lipid derivatives eicosanoids have been identified as important mediators that contribute to mechanisms of atherogenesis. Prostaglandins and thromboxane A2 are members of the eicosanoid family synthesized from arachidonic acid by the combined action of cyclooxygenases and prostaglandins and thromboxane A2 synthase. Thromboxane A2, a potent platelet activator and vasoconstrictor and prostacyclin, a platelet inhibitor and vasodilator, are the most important in the development of cardiovascular diseases. Several pro-atherogenic biological effects have also been attributed to isoprostanes, a class of eicosanoid isomers formed via a free radical-mediated oxidation of fatty acids esterified in membrane phospholipids. Both groups of lipids manifest their biological activities by binding to specific receptors in target cells. In this article, we will describe the biological roles of prostacyclin, thromboxane A2 and isoprostanes in atherogenesis and discuss the latest pharmacological studies assessing the therapeutic effects of drugs that specifically target their biosynthesis and/or biological activities on vascular inflammation and atherosclerotic lesion development.
Why do humans reason? Arguments for an argumentative theory (2011)

Reasoning is generally seen as a means to improve knowledge and make better decisions. However, much evidence shows that reasoning often leads to epistemic distortions and poor decisions. This suggests that the function of reasoning should be rethought. Our hypothesis is that the function of reasoning is argumentative. It is to devise and evaluate arguments intended to persuade. Reasoning so conceived is adaptive given the exceptional dependence of humans on communication and their vulnerability to misinformation. A wide range of evidence in the psychology of reasoning and decision making can be reinterpreted and better explained in the light of this hypothesis. Poor performance in standard reasoning tasks is explained by the lack of argumentative context. When the same problems are placed in a proper argumentative setting, people turn out to be skilled arguers. Skilled arguers, however, are not after the truth but after arguments supporting their views. This explains the notorious confirmation bias. This bias is apparent not only when people are actually arguing, but also when they are reasoning proactively from the perspective of having to defend their opinions. Reasoning so motivated can distort evaluations and attitudes and allow erroneous beliefs to persist. Proactively used reasoning also favors decisions that are easy to justify but not necessarily better. In all these instances traditionally described as failures or flaws, reasoning does exactly what can be expected of an argumentative device: Look for arguments that support a given conclusion, and, ceteris paribus, favor conclusions for which arguments can be found.