gebhart/patrepeval huggingface dataset:
A General and Efficient Copper Catalyst for the Amidation of Aryl Halides (2002)

An experimentally simple and inexpensive catalyst system was developed for the amidation of aryl halides by using 0.2-10 mol % of CuI, 5-20 mol % of a 1,2-diamine ligand, and K(3)PO(4), K(2)CO(3), or Cs(2)CO(3) as base. Catalyst systems based on N,N'-dimethylethylenediamine or trans-N,N'-dimethyl-1,2-cyclohexanediamine were found to be the most active even though several other 1,2-diamine ligands could be used in the easiest cases. Aryl iodides, bromides, and in some cases even aryl chlorides can be efficiently amidated. A variety of functional groups are tolerated in the reaction, including many that are not compatible with Pd-catalyzed amidation or amination methodology.
Recurrent GNAS Mutations Define an Unexpected Pathway for Pancreatic Cyst Development (2011)

More than 2% of the adult U.S. population harbors a pancreatic cyst. These often pose a difficult management problem because conventional criteria cannot always distinguish cysts with malignant potential from those that are innocuous. One of the most common cystic neoplasms of the pancreas, and a bona fide precursor to invasive adenocarcinoma, is called intraductal papillary mucinous neoplasm (IPMN). To help reveal the pathogenesis of these lesions, we purified the DNA from IPMN cyst fluids from 19 patients and searched for mutations in 169 genes commonly altered in human cancers. In addition to the expected KRAS mutations, we identified recurrent mutations at codon 201 of GNAS. A larger number (113) of additional IPMNs were then analyzed to determine the prevalence of KRAS and GNAS mutations. In total, we found that GNAS mutations were present in 66% of IPMNs and that either KRAS or GNAS mutations could be identified in 96%. In eight cases, we could investigate invasive adenocarcinomas that developed in association with IPMNs containing GNAS mutations. In seven of these eight cases, the GNAS mutations present in the IPMNs were also found in the invasive lesion. GNAS mutations were not found in other types of cystic neoplasms of the pancreas or in invasive adenocarcinomas not associated with IPMNs. In addition to defining a new pathway for pancreatic neoplasia, these data suggest that GNAS mutations can inform the diagnosis and management of patients with cystic pancreatic lesions.
The gas permeability coefficient of the cyanobacterial gas vesicle wall (1992)

Summary: The gas permeability coefficient of the cyanobacterial gas vesicle wall has been determined by comparing the concentration gradient of oxygen gas in a film of gas vesicles with the gradient in an underlying film of agar supported over an oxygen atmosphere. The gradients were determined with an oxygen microelectrode. The value of the gradient in aqueous agar was 0·81 of that in a suspension in which gas vesicles occupied 0·35 of the total volume. From this it was calculated that the notional diffusivity of oxygen through the gas vesicle was equivalent to 0·53 of the diffusivity in water. The permeability coefficient of the gas vesicle membrane is calculated to be k = 32 mm s −1, the rate coefficient for filling the gas vesicle by diffusion is a = 2·4 x 106 s −1 and the folding time for equilibration of gas into a gas vesicle is t e = 0·4 μs. The permeability coefficient is about 100-fold higher than the minimum value set by previous pressure rise experiments, and confirms that gas vesicles could not store gas. The measurements also show, however, that randomly oriented gas vesicles would not provide a diffusion channel with a diffusivity higher than that in water, although a layer of gas vesicles oriented with their long axes parallel to the diffusion gradient would provide a diffusivity 3·5-fold higher. The determination of the diffusivity was made with a theory, based on diffusion equations, which can be used in the determination of the diffusivity through other cell organelles.
Hypertension and dysregulated proinflammatory cytokine production in receptor activity-modifying protein 1-deficient mice (2007)

Calcitonin gene-related peptide (CGRP) is thought to be a prominent neuropeptide in cardiovascular regulation and neuroimmune modulation. There are two isoforms of CGRP (alphaCGRP and betaCGRP), and the main CGRP receptors are probably composed of a calcitonin receptor-like receptor (CLR) and a receptor activity-modifying protein (RAMP)1. However, the physiological functions of CGRP that are mediated through the CLR/RAMP1 receptors remain to be clarified. For an improved understanding of the functions, we generated mice deficient in RAMP1, a specific subunit of CGRP receptors, by a conditional gene-targeting technique. The RAMP1-deficient mice (RAMP1(-/-)) exhibited high blood pressure, with no changes in heart rate. alphaCGRP was found to have a potent vascular relaxant activity compared with betaCGRP in the artery of the WT (RAMP1(+/+)) mice. The activities of both CGRP isoforms were remarkably suppressed in the arteries of the RAMP1(-/-) mice. The LPS-induced inflammatory responses of the RAMP1(-/-) mice revealed a transient and significant increase in the serum CGRP levels and high serum levels of proinflammatory cytokines compared with the RAMP1(+/+) mice. alphaCGRP and betaCGRP equally suppressed the production of TNF-alpha and IL-12 in bone marrow-derived dendritic cells stimulated with lipopolysaccharide. Their inhibitory effects were not observed in the bone marrow-derived dendritic cells of the RAMP1(-/-) mice. These results indicate that CGRP signaling through CLR/RAMP1 receptors plays a crucial role in the regulation of both blood pressure by vascular relaxation and proinflammatory cytokine production from dendritic cells.
BMP-1: Resurrection As Procollagen C-Proteinase (1996)

The characterization of the function of bone morphogenetic protein-1 (BMP-1) was reported in last week's issue of Science (19 January, p. 360) . In his Perspective, A. H. Reddi explains why it was surprising (and important) that BMP-1 turned out to be identical to procollagen C-proteinase, the enzyme responsible for triggering the self-assembly of collagen.
Bayesian Networks-Based Approach for Power Systems Fault Diagnosis (2006)

In this paper, three element-oriented models based on simplified Bayesian networks with Noisy-Or and Noisy-And nodes are proposed to estimate the faulty section of a transmission power system. The three models are used to test if any transmission line, transformer, or busbar within a blackout area is faulty. They can deal with uncertain or incomplete data and knowledge relating to power system diagnosis, so they are flexible. The structures and initial parameters of the Bayesian networks depend on the prior knowledge of the domain experts. The parameters can be revised by using an error back propagation algorithm similar to the back-propagation algorithm for artificial neural networks. The fault diagnosis models do not vary with the change of the network structure, so they can be applied to any transmission power system. Furthermore, they have clear semantics, rapid reasoning, powerful error tolerance ability, and no convergence problem during the diagnosing procedure. Experimental tests show that the approach is feasible and efficient, so the prototype program based on the approach is promising to be used in a large transmission power system for online fault diagnosis.
Basement Membrane Proteins: Structure, Assembly, and Cellular Interactions (1992)

Basement membranes are thin layers of a specialized extracellular matrix that form the supporting structure on which epithelial and endothelial cells grow, and that surround muscle and fat cells and the Schwann cells of peripheral nerves. One common denominator is that they are always in close apposition to cells, and it has been well demonstrated that basement membranes do not only provide a mechanical support and divide tissues into compartments, but also influence cellular behavior. The major molecular constituents of basement membranes are collagen IV, laminin-entactin/nidogen complexes, and proteoglycans. Collagen IV provides a scaffold for the other structural macromolecules by forming a network via interactions between specialized N- and C-terminal domains. Laminin-entactin/nidogen complexes self-associate into less-ordered aggregates. These two molecular assemblies appear to be interconnected, presumably via binding sites on the entactin/nidogen molecule. In addition, proteoglycans are anchored into the membrane by an unknown mechanism, providing clusters of negatively charged groups. Specialization of different basement membranes is achieved through the presence of tissue-specific isoforms of laminin and collagen IV and of particular proteoglycan populations, by differences in assembly between different membranes, and by the presence of accessory proteins in some specialized basement membranes. Many cellular responses to basement membrane proteins are mediated by members of the integrin class of transmembrane receptors. On the intracellular side some of these signals are transmitted to the cytoskeleton, and result in an influence on cellular behavior with respect to adhesion, shape, migration, proliferation, and differentiation. Phosphorylation of integrins plays a role in modulating their activity, and they may therefore be a part of a more complex signaling system.
Design of a WDM network using a multiple ring approach (2002)

This paper introduces a new all-optical network design approach using a multiple ring concept as an alternative to the present mesh network scheme. It is shown that several different design alternatives using multiple rings exist and they can be classified into two categories according to the way in which the traffic is accommodated. The one that offers the most simple control and management has been investigated and is discussed here. It is shown that this approach can be very useful for the design and implementation of wavelength division multiplexing networks as it offers many useful advantages of the ring structure while is still able to achieve the high efficiency of network bandwidth usage due to high connectivity in the mesh topology. For example, in the sample network considered here the multiple ring scheme only requires less than 10% extra capacity in comparison to the pure mesh design.
Ternary Pt-Ru-Ni catalytic layers for methanol electrooxidation prepared by electrodeposition and galvanic replacement (2014)

Ternary Pt-Ru-Ni deposits on glassy carbon substrates, Pt-Ru(Ni)/GC, have been formed by initial electrodeposition of Ni layers onto glassy carbon electrodes, followed by their partial exchange for Pt and Ru, upon their immersion into equimolar solutions containing complex ions of the precious metals. The overall morphology and composition of the deposits has been studied by SEM microscopy and EDS spectroscopy. Continuous but nodular films have been confirmed, with a Pt ÷ Ru ÷ Ni % bulk atomic composition ratio of 37 ÷ 12 ÷ 51 (and for binary Pt-Ni control systems of 47 ÷ 53). Fine topographical details as well as film thickness have been directly recorded using AFM microscopy. The composition of the outer layers as well as the interactions of the three metals present have been studied by XPS spectroscopy and a Pt ÷ Ru ÷ Ni % surface atomic composition ratio of 61 ÷ 12 ÷ 27 (and for binary Pt-Ni control systems of 85 ÷ 15) has been found, indicating the enrichment of the outer layers in Pt; a shift of the Pt binding energy peaks to higher values was only observed in the presence of Ru and points to an electronic effect of Ru on Pt. The surface electrochemistry of the thus prepared Pt-Ru(Ni)/GC and Pt(Ni)/GC electrodes in deaerated acid solutions (studied by cyclic voltammetry) proves the existence of a shell consisting exclusively of Pt-Ru or Pt. The activity of the Pt-Ru(Ni) deposits toward methanol oxidation (studied by slow potential sweep voltammetry) is higher from that of the Pt(Ni) deposit and of pure Pt; this enhancement is attributed both to the well-known Ru synergistic effect due to the presence of its oxides but also (based on the XPS findings) to a modification effect of Pt electronic properties.
Image melding (2012)

Current methods for combining two different images produce visible artifacts when the sources have very different textures and structures. We present a new method for synthesizing a transition region between two source images, such that inconsistent color, texture, and structural properties all change gradually from one source to the other. We call this process image melding . Our method builds upon a patch-based optimization foundation with three key generalizations: First, we enrich the patch search space with additional geometric and photometric transformations. Second, we integrate image gradients into the patch representation and replace the usual color averaging with a screened Poisson equation solver. And third, we propose a new energy based on mixed L 2 /L 0 norms for colors and gradients that produces a gradual transition between sources without sacrificing texture sharpness. Together, all three generalizations enable patch-based solutions to a broad class of image melding problems involving inconsistent sources: object cloning, stitching challenging panoramas, hole filling from multiple photos, and image harmonization. In several cases, our unified method outperforms previous state-of-the-art methods specifically designed for those applications.
Discovery of Novel PI3-Kinase δ Specific Inhibitors for the Treatment of Rheumatoid Arthritis: Taming CYP3A4 Time-Dependent Inhibition (2012)

PI3Kδ is a lipid kinase and a member of a larger family of enzymes, PI3K class IA(α, β, δ) and IB (γ), which catalyze the phosphorylation of PIP2 to PIP3. PI3Kδ is mainly expressed in leukocytes, where it plays a critical, nonredundant role in B cell receptor mediated signaling and provides an attractive opportunity to treat diseases where B cell activity is essential, e.g., rheumatoid arthritis. We report the discovery of novel, potent, and selective PI3Kδ inhibitors and describe a structural hypothesis for isoform (α, β, γ) selectivity gained from interactions in the affinity pocket. The critical component of our initial pharmacophore for isoform selectivity was strongly associated with CYP3A4 time-dependent inhibition (TDI). We describe a variety of strategies and methods for monitoring and attenuating TDI. Ultimately, a structure-based design approach was employed to identify a suitable structural replacement for further optimization.
Prostate-specific Antigen and Human Glandular Kallikrein: Two Kallikreins of the Human Prostate (1994)

Prostate-specific antigen (PSA) is a 33 kD protein synthesized in the epithelial cells of the prostate gland. It is a serine protease that belongs to the subgroup of kallikreins, among which it is very similar to a putative enzyme called human glandular kallikrein (hGK-1). Although the hGK-1 enzyme remains to be characterized in vivo, the hGK-1 gene is expressed in the same prostatic epithelial cells as the PSA gene. Expression of the PSA gene is under complex control and the steady-state level of PSA mRNA is increased by androgens, and decreased by epidermal growth factor and activation of protein kinase C. This suggests the existence of several regulatory elements within the cis-acting control elements of the PSA gene. As a seminal serine protease, PSA has been shown to digest the high molecular weight seminal vesicle protein, seminogelin. However, it is likely that this does not constitute the only natural substrate of PSA, as PSA has been shown to degrade insulin-like growth factor-binding protein-3. Serum PSA concentrations are frequently increased in patients with prostatic cancer, but this is also the case in patients with benign prostatic hyperplasia. Thus, PSA measurements alone are not useful as a screening tool for undiagnosed prostatic cancer. However, serum PSA concentrations can be successfully used together with other methods in diagnosing prostatic diseases and in monitoring the successfulness of treatments for prostatic cancer.
Simultaneous Analysis of the Majority of Low-Molecular-Weight, Redox-Active Compounds from Mitochondria (1998)

Studies of the interaction between oxidative stress and mitochondrial dysfunction are complicated by analytical limitations, especially the need to assess multiple parameters in relatively small samples. We have addressed this problem by developing a methodology for the simultaneous analysis of the majority of low-molecular-weight, redox-active compounds from mitochondria using HPLC separations followed by coulometric array detection. The method described should also be applicable for the study of redox-active compounds in other subcellular organelles as well as in intact cells and tissues. The protocol described enables simultaneous measurement of antioxidants (e.g., tocopherols, ascorbate, lipoates, uric acid, and glutathione), markers of oxidative stress (e.g., o-tyrosine, m-tyrosine, nitrotyrosine, dityrosine, glutathione disulfide, and 8-hydroxydeoxyguanosine) as well as other metabolites (e.g., purines and indoles). In all, ca. 600 redox active compounds can be detected, most with a limit of detection of approximately 5 pg on column. Results, including analytical parameters, from a study of liver mitochondria from control and diabetic rats are presented to demonstrate utility of this methodology.
Analysis of Pseudomonas exotoxin activation and conformational changes by using monoclonal antibodies as probes (1991)

Pseudomonas exotoxin (PE) is a protein toxin composed of three structural domains. In its native form, the toxin is a 66,000-Mr proenzyme that must be activated to express full ADP-ribosylating activity. To study the process of activation and accompanying conformational changes, we have isolated 10 monoclonal antibodies to a 40,000-Mr fragment of the toxin (PE40) that exhibits full enzyme activity but lacks the toxin's cell-binding domain and contains amino acids 253 to 613 (comprising domains II, Ib, and III). By using mutant PE molecules in which all of domain I and portions of domains II, Ib, and III were deleted, the locations of the epitopes for each of the antibodies were determined. Eight of these monoclonal antibodies were further characterized. Of these eight, all reacted with soluble PE40 and an interleukin-2-PE40 conjugate, but only two reacted strongly with native soluble PE. However, all eight reacted with PE after it had been immobilized on nitrocellulose or after it had been activated to express full ADP-ribosylating activity. Antibodies were also assessed for their ability to neutralize the cytotoxic activity of either PE or interleukin-2-PE40. These antibodies should be useful as probes for monitoring the activation and processing of PE that occur during endocytosis and in determining the location of epitopes that are important for toxin activity.
Mitogen-activated protein kinase kinase 1 (MKK1) is negatively regulated by threonine phosphorylation. (1994)

Mitogen-activated protein kinase kinase 1 (MKK1), a dual-specificity tyrosine/threonine protein kinase, has been shown to be phosphorylated and activated by the raf oncogene product as part of the mitogen-activated protein kinase cascade. Here we report the phosphorylation and inactivation of MKK1 by phosphorylation on threonine 286 and threonine 292. MKK1 contains a consensus phosphorylation site for p34cdc2, a serine/threonine protein kinase that regulates the cell division cycle, at Thr-286 and a related site at Thr-292. p34cdc2 catalyzes the in vitro phosphorylation of MKK1 on both of these threonine residues and inactivates MKK1 enzymatic activity. Both sites are phosphorylated in vivo as well. The data presented in this report provide evidence that MKK1 is negatively regulated by threonine phosphorylation.
Characterization of p150, an Adaptor Protein for the Human Phosphatidylinositol (PtdIns) 3-Kinase (1997)

Genetic and biochemical studies have shown that the phosphatidylinositol (PtdIns) 3-kinase encoded by the yeast VPS34 gene is required for the efficient sorting and delivery of proteins to the vacuole. A human homologue of the yeast VPS34 gene product has recently been characterized as part of a complex with a cellular protein of 150 kDa (Volinia, S., Dhand, R., Vanhaesebroeck, B., MacDougall, L. K., Stein, R., Zvelebil, M. J., Domin, J., Panaretou, C., and Waterfield, M. D. (1995) EMBO J. 14, 3339-3348). Here, cDNA cloning is used to show that the amino acid sequence of this protein, termed p150, is 29.6% identical and 53% similar to the yeast Vps15p protein, an established regulator of Vps34p. Northern blot analysis showed a ubiquitous tissue distribution for p150 similar to that previously observed with PtdIns 3-kinase. Recombinant p150 associated with PtdIns 3-kinase in vitro in a stable manner, resulting in a 2-fold increase in lipid kinase activity. Addition of phosphatidylinositol transfer protein (PI-TP) further stimulated the lipid kinase activity of the p150.PtdIns 3-kinase complex 3-fold. A PtdIns 3-kinase activity could also be co-immunoprecipitated from human cell lysates using anti-PI-TP antisera. This observation demonstrates that an interaction between a PtdIns 3-kinase and PI-TP occurs in vivo, which further implicates lipid transfer proteins in the regulation of PtdIns 3-kinase activity. These results suggest that the Vps15p.Vps34p complex has been conserved from yeast to man and in both species is involved in protein trafficking.
Activation of the respiratory burst oxidase in a fully soluble system from human neutrophils. (1987)

The O2(-)-forming respiratory burst oxidase is present in a dormant state in a fully soluble system containing both cytosol and a deoxycholate extract of membranes from resting human neutrophils. Sodium dodecyl sulfate at low concentrations converts this soluble dormant oxidase into its catalytically active form. The Vmax for the activated oxidase was 2.1 mumol of O2-/min/mg of membrane protein. Michaelis constants for NADPH and NADH (38 microM and 1.7 mM, respectively) were similar to those measured previously in other systems. Oxidase activity was not detected after sodium dodecyl sulfate treatment of systems containing solubilized neutrophil membranes obtained from patients with X-linked chronic granulomatous disease. These results suggest that the deoxycholate extract contains both the resting oxidase and those membrane-associated components needed for its activation, all in functioning states.