gebhart/patrepeval huggingface dataset:
Abstract 1101: Cardio-protective Action of Follistatin Like-1, a Secreted Anti-apoptotic Factor Regulated by Akt1 (2007)

Recent reports have proposed the importance of secreted factors that display cardioprotective effects through autocrine / paracrine mechanisms. Identification of these factors will provide novel th...
Structural comparison of CuII complexes in atom transfer radical polymerization (2002)

The molecular structures of [CuII(dNbpy)2Br]+[CuIBr2]−, CuII(pmdeta)Br2, CuII(tNtpy)Br2, [CuII(hmteta)Br]+[Br]− and [CuII(cyclam)Br]+[Br]− [dNbpy = 4,4′-di(5-nonyl)-2,2′-bipyridine, pmdeta = N,N,N′,N″,N″-pentamethyldiethylenetriamine, tNtpy = 4,4′,4″-tris(5-nonyl)-2,2′:6′,2″-terpyridine, hmteta = 1,1,4,7,10,10-hexamethyltriethylenetetramine, Me4cyclam = 1,4,8,11-tetraaza-1,4,8,11-tetramethylcyclotetradecane] isolated from atom transfer radical polymerizations (ATRP) were determined. The CuII complexes showed either a trigonal bipyramidal structure as in the case of the dNbpy ligand, or a distorted square pyramidal coordination in the case of triamines and tetramines. Depending on the type of amine ligand, the complexes were either neutral (triamines) or ionic (bpy and tetramines). The counterions in the case of the ionic complexes were either bromide (Me4cyclam and hmteta) or the linear [CuIBr2]− anion (dNbpy). No direct correlation was found between the CuII–Br bond length and the deactivation rate constant in ATRP, which suggests that other parameters such as the entropy for the structural reorganization between the CuI and CuII complexes might play an important role in determining the overall activity of the catalyst in ATRP.
A Biosynthetic Route to Photoclick Chemistry on Proteins (2010)

Light-induced chemical reactions exist in nature, regulating many important cellular and organismal functions, e.g., photosensing in prokaryotes and vision formation in mammals. Here, we report the genetic incorporation of a photoreactive unnatural amino acid, p-(2-tetrazole)phenylalanine (p-Tpa), into myoglobin site-specifically in E. coli by evolving an orthogonal tRNA/aminoacyl-tRNA synthetase pair and the use of p-Tpa as a bioorthogonal chemical "handle" for fluorescent labeling of p-Tpa-encoded myoglobin via the photoclick reaction. Moreover, we elucidated the structural basis for the biosynthetic incorporation of p-Tpa into proteins by solving the X-ray structure of p-Tpa-specific aminoacyl-tRNA synthetase in complex with p-Tpa. The genetic encoding of this photoreactive amino acid should make it possible in the future to photoregulate protein function in living systems.
The R1 component of mammalian ribonucleotide reductase has malignancy-suppressing activity as demonstrated by gene transfer experiments (1997)

Our recent studies have shown that deregulated expression of R2, the rate-limiting component of ribonucleotide reductase, enhances transformation and malignant potential by cooperating with activated oncogenes. We now demonstrate that the R1 component of ribonucleotide reductase has tumor-suppressing activity. Stable expression of a biologically active ectopic R1 in ras-transformed mouse fibroblast 10T(1/2) cell lines, with or without R2 overexpression, led to significantly reduced colony-forming efficiency in soft agar. The decreased anchorage independence was accompanied by markedly suppressed malignant potential in vivo. In three ras-transformed cell lines, R1 overexpression resulted in abrogation or marked suppression of tumorigenicity. In addition, the ability to form lung metastases by cells overexpressing R1 was reduced by >85%. Metastasis suppressing activity also was observed in the highly malignant mouse 10T(1/2) derived RMP-6 cell line, which was transformed by a combination of oncogenic ras, myc, and mutant p53. Furthermore, in support of the above observations with the R1 overexpressing cells, NIH 3T3 cells cotransfected with an R1 antisense sequence and oncogenic ras showed significantly increased anchorage independence as compared with control ras-transfected cells. Finally, characteristics of reduced malignant potential also were demonstrated with R1 overexpressing human colon carcinoma cells. Taken together, these results indicate that the two components of ribonucleotide reductase both are unique malignancy determinants playing opposing roles in its regulation, that there is a novel control point important in mechanisms of malignancy, which involves a balance in the levels of R1 and R2 expression, and that alterations in this balance can significantly modify transformation, tumorigenicity, and metastatic potential.
Metabotropic Glutamate Receptor 5-Induced Phosphorylation of Extracellular Signal-Regulated Kinase in Astrocytes Depends on Transactivation of the Epidermal Growth Factor Receptor (2001)

G-protein-coupled receptors (GPCRs) induce the phosphorylation of mitogen-activated protein (MAP) kinase by actions on any of a number of signal transduction systems. Previous studies have revealed that activation of the G(q)-coupled metabotropic glutamate receptor 5 (mGluR5) induces phosphorylation of the MAP kinase extracellular signal-regulated kinase 2 (ERK2) in cultured rat cortical astrocytes. We performed a series of studies to determine the mechanisms underlying mGluR5-induced phosphorylation of MAP kinase in these cells. Interestingly, our studies suggest that mGluR5-mediated ERK2 phosphorylation is dependent on the activation of G(alphaq) but is not mediated by the activation of phospholipase Cbeta1, activation of protein kinase C, or increases in intracellular calcium. Studies with peptide inhibitors suggest that this response is not dependent on G(betagamma) subunits. However, the activation of ERK2 was dependent on activation of the epidermal growth factor (EGF) receptor and activation of a Src family tyrosine kinase. Furthermore, activation of mGluR5 induced an association of this receptor and the EGF receptor, suggesting the formation of a signaling complex involved in the activation of ERK2. These data suggest that mGluR5 increases ERK2 phosphorylation in astrocytes by a novel mechanism involving the activation of G(alphaq) and both receptor and nonreceptor tyrosine kinases but that is independent of the activation of phospholipase Cbeta1.
Z3, a novel Jak2 tyrosine kinase small-molecule inhibitor that suppresses Jak2-mediated pathologic cell growth (2008)

Jak2 tyrosine kinase is essential for animal development and hyperkinetic Jak2 function has been linked to a host of human diseases. Control of this pathway using Jak2-specific inhibitors would therefore potentially serve as a useful research tool and/or therapeutic agent. Here, we used a high-throughput program called DOCK to predict the ability of 20,000 small molecules to interact with a structural pocket adjacent to the ATP-binding site of murine Jak2. One small molecule, 2-methyl-1-phenyl-4-pyridin-2-yl-2-(2-pyridin-2-ylethyl)butan-1-one (herein designated as Z3), bound to Jak2 with a favorable energy score. Z3 inhibited Jak2-V617F and Jak2-WT autophosphorylation in a dose-dependent manner but was not cytotoxic to cells at concentrations that inhibited kinase activity. Z3 selectively inhibited Jak2 kinase function with no effect on Tyk2 or c-Src kinase function. Z3 significantly inhibited proliferation of the Jak2-V617F-expressing, human erythroleukemia cell line, HEL 92.1.7. The Z3-mediated reduction in cell proliferation correlated with reduced Jak2 and STAT3 tyrosine phosphorylation levels as well as marked cell cycle arrest. Finally, Z3 inhibited the growth of hematopoietic progenitor cells isolated from the bone marrow of an essential thrombocythemia patient harboring the Jak2-V617F mutation and a polycythemia vera patient carrying a Jak2-F537I mutation. Collectively, the data suggest that Z3 is a novel specific inhibitor of Jak2 tyrosine kinase.
Assignment of functional domains involved in ADP-ribosylation and B-oligomer binding within the carboxyl terminus of the S1 subunit of pertussis toxin (1994)

The roles of the carboxyl terminus of the S1 subunit (composed of 235 amino acids) of pertussis toxin in the ADP-ribosylation of transducin (Gt) and in B-oligomer binding were defined by analysis of two carboxyl-terminal deletion mutants of the recombinant S1 (rS1) subunit: C204, which is composed of amino acids 1 through 204 of S1, and C219, which is composed of amino acids 1 through 219 of S1. C204 was expressed in Escherichia coli as a stable, soluble peptide that had an apparent molecular mass of 23.4 kDa. In a linear velocity assay, the specific activity of C180 was 2% and that of C204 was 80% of the activity displayed by rS1 in catalyzing the ADP-ribosylation of Gt. In addition, C204 possessed catalytic efficiencies (kcat/Km) that were 110% at variable Gt concentrations and 40% at variable NAD concentrations of those reported for rS1. These data showed that the catalytic activity of C204 approached the activity of S1. C204 and C219 were unable to associate with the B oligomer under conditions which promoted association of rS1 with the B oligomer. Consistent with these results, mixtures of C204 or C219 with the B oligomer did not elicit a clustering phenotype in CHO cells, whereas rS1 which had associated with the B oligomer was as cytotoxic as native pertussis toxin. These data indicate that residues between 219 and 235 are important in the association of the S1 subunit with the B oligomer. These data allow the assignment of functional regions to the carboxyl terminus of S1. Residues 195 to 204 are required for optimal ADP-ribosyltransferase activity, residues 205 to 219 link the catalytic region of S1 and a B-oligomer-binding region of S1, and residues 220 to 235 are required for association of S1 with the B oligomer.
A monoclonal antibody discriminating between subsets of T and B cells. (1981)

A description is given of a rat anti-mouse hybridoma antibody, JIId, which reacts with erythrocytes, neutrophils, greater than 90% of thymus cells, and most B cells. JIId does not have detectable activity for mature T cells, pluripotential stem cells, platelets, or cells of the monocyte-macrophage lineage. Although the JIId antigen is present on 90 to 95% of typical small B lymphocytes, pretreatment of spleen cells with JIId plus complement has no effect on secondary IgG antibody responses; by contrast, primary IgM responses and proliferative responses to lipopolysaccharide are substantially reduced. Unlike the precursors of IgG antibody-producing cells (AFC), IgG AFC per se are strongly JIId-positive. Rapid acquisition of the JIId antigen also applied to the early progeny of pluripotential stem cells.
Characterization of eds1, a mutation in Arabidopsis suppressing resistance to Peronospora parasitica specified by several different RPP genes. (1996)

The interaction between Arabidopsis and the biotrophic oomycete Peronospora parasitica (downy mildew) provides an attractive model pathosystem to identify molecular components of the host that are required for genotype-specific recognition of the parasite. These components are the so-called RPP genes (for resistance to P. parasitica). Mutational analysis of the ecotype Wassilewskija (Ws-0) revealed an RPP-nonspecific locus called EDS1 (for enhanced disease susceptibility) that is required for the function of RPP genes on chromosomes 3 (RPP1/RPP14 and RPP10) and 4 (RPP12). Genetic analyses demonstrated that the eds1 mutation is recessive and is not a defective allele of any known RPP gene, mapping to the bottom arm of chromosome 3 (approximately 13 centimorgans below RPP1/RPP14). Phenotypically, the Ws-eds1 mutant seedlings supported heavy sporulation by P. parasitica isolates that are each diagnostic for one of the RPP genes in wild-type Ws-0; none of the isolates is capable of sporulating on wild-type Ws-0. Ws-eds1 seedlings exhibited enhanced susceptibility to some P. parasitica isolates when compared with a compatible wild-type ecotype, Columbia, and the eds1 parental ecotype, Ws-0. This was observed as earlier initiation of sporulation and elevated production of conidiosporangia. Surprisingly, cotyledons of Ws-eds1 also supported low sporulation by five isolates of P. parasitica from Brassica oleracea. These isolates were unable to sporulate on > 100 ecotypes of Arabidopsis, including wild-type Ws-0. An isolate of Albugo candida (white blister) from B. oleracea also sporulated on Ws-eds1, but the mutant exhibited no alteration in phenotype when inoculated with several oomycete isolates from other host species. The bacterial resistance gene RPM1, conferring specific recognition of the avirulence gene avrB from Pseudomonas syringae pv glycinea, was not compromised in Ws-eds1 plants. The mutant also retained full responsiveness to the chemical inducer of systemic acquired resistance, 2,6-dichloroisonicotinic acid; Ws-eds1 seedlings treated with 2,6-dichloroisonicotinic acid became resistant to the Ws-0-compatible and Ws-0-incompatible P. parasitica isolates Emwa1 and Noco2, respectively. In summary, the EDS1 gene appears to be a necessary component of the resistance response specified by several RPP genes and is likely to function upstream from the convergence of disease resistance pathways in Arabidopsis.
Polymerization of Butadiene and Isoprene with Lanthanide Catalysts; Characterization and Properties of Homopolymers and Copolymers (1985)

Abstract The lanthanide polymerization catalysts represent a significant achievement in the synthesis of stereospecific high- cis cis -polybutadiene, high- cis cis -polyisoprene, and high cis random and block copolymers of butadiene with isoprene. In contrast to the conventional 3d transition metal catalysts, changes in lanthanide metals, halogens, and ligands do not significantly affect the cis -1,4 content of the polymer. But, the catalyst activity is greatly dependent on the choice of lanthanide elements, counterions, and donor ligands. Energy efficient processes are possible by performing the polymerizations in low boiling aliphatic hydrocarbon solvents with high solids content and possibly, in the gas phase. In addition, the described lanthanide catalysts are very effective for producing high cis polymers with a broad range of molecular weights.
Prognosis for total control of complex partial and secondarily generalized tonic clonic seizures (1996)

The overall prognosis for control of seizures of any type for 12 months was best for those who had only GTC at entry (55% and 48%), worst for those who had only CPS at entry (23% and 26%), and intermediate for those with MIXED seizures at entry (32% and 25%) (all p < 0.0001). Prognosis can be based on the predominant seizure type in patients with multiple types.
MAP estimation, linear programming and belief propagation with convex free energies (2007)

Finding the most probable assignment (MAP) in a general graphical model is known to be NP hard but good approximations have been attained with max-product belief propagation (BP) and its variants. In particular, it is known that using BP on a single-cycle graph or tree reweighted BP on an arbitrary graph will give the MAP solution if the beliefs have no ties. In this paper we extend the setting under which BP can be used to provably extract the MAP. We define Convex BP as BP algorithms based on a convex free energy approximation and show that this class includes ordinary BP with single-cycle, tree reweighted BP and many other BP variants. We show that when there are no ties, fixed-points of convex max-product BP will provably give the MAP solution. We also show that convex sum-product BP at sufficiently small temperatures can be used to solve linear programs that arise from relaxing the MAP problem. Finally, we derive a novel condition that allows us to derive the MAP solution even if some of the convex BP beliefs have ties. In experiments, we show that our theorems allow us to find the MAP in many real-world instances of graphical models where exact inference using junction-tree is impossible. 1
Brillouin gain spectrum characterization in single-mode optical fibers (1997)

A novel method for Brillouin gain spectrum measurements in optical fibers is presented. It is based on the pump and probe technique with the specificity to use a single laser source together with an external modulator to generate the interacting lightwaves. The high accuracy and inherent stability of the technique makes it suitable for calibration and reference measurements. Different fibers with different refractive index profiles have been tested and characterized. The problem of the evolution of the polarization of the interacting waves is addressed in the article and a polarization insensitive determination of the actual Brillouin gain coefficient is made possible through two successive measurements with different polarizations. The effects of strain and temperature on the Brillouin gain spectrum are also fully characterized.
Identification of peptide sequences that potentially trigger HLA‐A2.1‐restricted cytotoxic T lymphocytes (1993)

We used the human processing defective cell line 174CEM.T2 (T2) to identify potential cytotoxic T lymphocyte (CTL) epitopes of human proteins. Exogenously added peptides can increase the number of properly folded HLA-A2.1 molecules on the cell surface of T2 cells, as shown by immunofluorescence measurements using the mouse monoclonal antibody BB7.2 (anti-HLA-A2.1) and fluorescein isothiocyanate-labeled goat anti-mouse F(ab')2 antibody. The peptides were selected on the basis of a computer score derived from the recently described HLA-A2.1 specific motif. Analysis of the influenza matrix protein showed that 15 out of 35 high-scoring peptides up-regulate the expression of HLA-A2.1 molecules on the T2 cell surface. The combination of the computer scoring program and an immunofluorescence-based peptide binding assay allows rapid detection of potential CTL target peptides.
Elevated levels of glyoxylate shunt enzymes in Escherichia coli strains constitutive for fatty acid degradation (1980)

Mutants of Escherichia coli K-12 constitutive for the synthesis of the enzymes of fatty acid degradation (fadR) have elevated levels of the glyoxylate shunt enzymes, isocitrate lyase and malate synthase. A temperature-sensitive fadR strain has high levels of glyoxylate shunt enzymes when grown at elevated temperatures but has low, inducible levels of glyoxylate shunt enzymes when grown at low temperatures. The increased activity of glyoxylate shunt enzymes did not appear to be due to the degradation of intracellular fatty acids in fadR strains or differences in allosteric effectors in fadR versus fadR+ strains. These studies suggest that the fadR gene product may be involved in the regulation of the glyoxylate operon.
Optics at critical intensity: Applications to nanomorphing (2004)

Laser-induced optical breakdown by femtosecond pulses is extraordinarily precise when the energy is near threshold. Despite numerous applications, the basis for this deterministic nature has not been determined. We present experiments that shed light on the basic mechanisms of light-matter interactions in this regime, which we term "optics at critical intensity." We find that the remarkably sharp threshold for laser-induced material damage enables the structure or properties of materials to be modified with nanometer precision. Through detailed study of the minimum ablation size and the effects of polarization, we propose a fundamental framework for describing light-matter interactions in this regime. In surprising contrast to accepted damage theory, multiphoton ionization does not play a significant role. Our results also reject the use of the Keldysh parameter in predicting the role of multiphoton effects. We find that the dominant mechanism is Zener ionization followed by a combination of Zener and Zener-seeded avalanche ionization. We predict that the minimum feature size ultimately depends on the valence electron density, which is sufficiently high and uniform, to confer deterministic behavior on the damage threshold even at the nanoscale. This behavior enables nanomachining with high precision, which we demonstrate by machining highly reproducible nanometer-sized holes and grooves in dielectrics.
Max: A Helix-Loop-Helix Zipper Protein That Forms a Sequence-Specific DNA-Binding Complex with Myc (1991)

The myc protooncogene family has been implicated in cell proliferation, differentiation, and neoplasia, but its mechanism of function at the molecular level is unknown. The carboxyl terminus of Myc family proteins contains a basic region helix-loop-helix leucine zipper motif (bHLH-Zip), which has DNA-binding activity and has been predicted to mediate protein-protein interactions. The bHLH-Zip region of c-Myc was used to screen a complementary DNA (cDNA) expression library, and a bHLH-Zip protein, termed Max, was identified. Max specifically associated with c-Myc, N-Myc, and L-Myc proteins, but not with a number of other bHLH, bZip, or bHLH-Zip proteins. The interaction between Max and c-Myc was dependent on the integrity of the c-Myc HLH-Zip domain, but not on the basic region or other sequences outside the domain. Furthermore, the Myc-Max complex bound to DNA in a sequence-specific manner under conditions where neither Max nor Myc exhibited appreciable binding. The DNA-binding activity of the complex was dependent on both the dimerization domain and the basic region of c-Myc. These results suggest that Myc family proteins undergo a restricted set of interactions in the cell and may belong to the more general class of eukaryotic DNA-binding transcription factors.
Rapid Identification of Antifungal Compounds against Exserohilum rostratum Using High Throughput Drug Repurposing Screens (2013)

A recent large outbreak of fungal infections by Exserohilum rostratum from contaminated compounding solutions has highlighted the need to rapidly screen available pharmaceuticals that could be useful in therapy. The present study utilized two newly-developed high throughput assays to screen approved drugs and pharmaceutically active compounds for identification of potential antifungal agents. Several known drugs were found that have potent effects against E. rostratum including the triazole antifungal posaconazole. Posaconazole is likely to be effective against infections involving septic joints and may provide an alternative for refractory central nervous system infections. The anti-E. rostratum activities of several other drugs including bithionol (an anti-parasitic drug), tacrolimus (an immunosuppressive agent) and floxuridine (an antimetabolite) were also identified from the drug repurposing screens. In addition, activities of other potential antifungal agents against E. rostratum were excluded, which may avoid unnecessary therapeutic trials and reveals the limited therapeutic alternatives for this outbreak. In summary, this study has demonstrated that drug repurposing screens can be quickly conducted within a useful time-frame. This would allow clinical implementation of identified alternative therapeutics and should be considered as part of the initial public health response to new outbreaks or rapidly-emerging microbial pathogens.