gebhart/patrepeval huggingface dataset:
Discovery of Low‐Molecular‐Weight Ligands for the AF6 PDZ Domain (2006)

In the groove: The “drugability” of protein–protein interaction domains is still a matter of debate. The 3D structure of a complex of a small organic ligand and the AF6 PDZ domain revealed the creation of a binding pocket by the ligand (see picture). The derived compound is able to compete with a natural peptide ligand of the domain and represents a basic building block for the generation of selective PDZ inhibitors. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2006/z503965_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Efficient Packaging of Readthrough RNA in ALV: Implications for Oncogene Transduction (1987)

Readthrough viral transcripts are present at relatively high levels in cells infected with avian leukosis virus. It has been proposed that they can function as intermediates in the transduction of proto-oncogenes by retroviruses. It is shown here, by the analysis of viruses containing a mutation in the AAUAAA polyadenylation signal, that readthrough RNAs have the requisite properties to function as transduction intermediates: (i) readthrough RNAs were polyadenylated and packaged as efficiently as normal viral RNA, (ii) RNAs nearly 11.2 kilobases (3.5 kilobases larger than wild-type avian leukosis virus genomes) were present in virions of the mutant virus, and (iii) virus particles containing both readthrough and normal genomes were most likely infectious.
Intra Subject Variability of Progesterone 200 mg Soft Capsules in Indian Healthy Adult Postmenopausal Female Subjects under Fasting Conditions (2014)

The aim of this study was to evaluate the intra subject variability of progesterone 200 mg soft capsules of Test product with Prometrium® (Progesterone USP) capsules 200 mg (Reference) marketed by Solvay Pharmaceuticals Inc., Marietta, GA in healthy adult, human, post-menopausal female volunteers. This study was an open label, randomized, balanced, single-dose, two sequence two period, crossover oral bioequivalence study was conducted in 12 healthy adult, human, post-menopausal female volunteers under fasting conditions. Subjects received progesterone 200 mg of either test or reference formulation with a washout period of 10 days. After study drug administration, serial blood samples were collected over a period of 36 hours post dose. The plasma concentrations of progesterone were determined by a validated method using LC/MS/MS. Pharmacokinetic parameters Cmax, Tmax, AUC0-t, AUC0-∞, Kel and T1/2 were determined for both the formulations. The formulations were to be considered bioequivalent if the geometric least square mean ratio of test and reference of Cmax, AUC0-t and AUC0-∞ were within the predetermined bioequivalence range of 80% to 125%. A total of 12 subjects were enrolled. No significant differences were found based on analysis of variance. The 90% confidence intervals (CI) of Cmax, AUC0-t and AUC0-∞, of progesterone were 52.10-148.80%, 52.66-164.84%, and 56.05-152.68% respectively. The test formulation in this study fails to show the bioequivalence with that of reference formulation for progesterone. The intra subject variability (%) for Cmax, AUC0-t and AUC0-∞ were found to be 68.2, 75.6 and 64.6 respectively. There was significant intra subject variability was observed for progesterone under fed conditions.
Database Tuning: Principles, Experiments, and Troubleshooting Techniques. (2002)

Tuning your database for optimal performance means more than following a few short steps in a vendor-specific guide. For maximum improvement, you need a broad and deep knowledge of basic tuning principles, the ability to gather data in a systematic way, and the skill to make your system run faster. This is an art as well as a science, and Database Tuning: Principles, Experiments, and Troubleshooting Techniques will help you develop portable skills that will allow you to tune a wide variety of database systems on a multitude of hardware and operating systems. Further, these skills, combined with the scripts provided for validating results, are exactly what you need to evaluate competing database products and to choose the right one.
Tyrosinase Inhibition Kinetics of Anisic Acid (2003)

Anisic acid (p-methoxybenzoic acid) was characterized as a tyrosinase inhibitor from ani-seed, a common food spice. It inhibited the oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) catalyzed by tyrosinase with an IC50 of 0.60 mM. The inhibition of tyrosinase by anisic acid is a reversible reaction with residual enzyme activity. This phenolic acid was found to be a classical noncompetitive inhibitor and the inhibition constant K(I) was obtained as 0.603 mM. Anisic acid also inhibited the hydroxylation of L-tyrosine catalyzed by tyrosinase. The lag phase caused by the monophenolase activity was lengthened and the steady-state activity of the enzyme was decreased by anisic acid.
Down-regulation of Forkhead Box M1 Transcription Factor Leads to the Inhibition of Invasion and Angiogenesis of Pancreatic Cancer Cells (2007)

The Forkhead Box M1 (FoxM1) transcription factor has been shown to play important roles in regulating the expression of genes involved in cell proliferation, differentiation, and transformation. Overexpression of FoxM1 has been found in a variety of aggressive human carcinomas including pancreatic cancer. However, the precise role and the molecular mechanism of action of FoxM1 in pancreatic cancer remain unclear. To elucidate the cellular and molecular function of FoxM1, we tested the consequences of down-regulation and up-regulation of FoxM1 in pancreatic cancer cells, respectively. Using multiple cellular and molecular approaches such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, gene transfection, flow cytometry, real-time reverse transcription-PCR, Western blotting, migration, invasion, and angiogenesis assays, we found that down-regulation of FoxM1 inhibited cell growth, decreased cell migration, and decreased invasion of pancreatic cancer cells. FoxM1 down-regulation also decreased cell population in the S phase. Compared with control, FoxM1 small interfering RNA-transfected cells showed decreased expression of cyclin B, cyclin D1, and Cdk2, whereas p21 and p27 expression was increased. We also found that down-regulation of FoxM1 reduced the expression of matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor, resulting in the inhibition of migration, invasion, and angiogenesis. These findings suggest that FoxM1 down-regulation could be a novel approach for the inhibition of pancreatic tumor progression.
Hematopoietic Stem-cell Transplantation Using Umbilical-cord Blood (2003)

In the recent years, umbilical cord blood (UCB) has emerged as an alternative source of hematopoietic progenitors (CD34+) for allogeneic stem cell transplantation, mainly in patients lacking an HLA-matched marrow donor. Since 1998, about 2500 patients have received UCB transplants for a variety of malignant and non-malignant diseases. The vast majority of recipients were children with an average weight of 20kg, however, more than 500 UCB transplantations (UCBT) have already been performed in adults. The "naive" nature of UCB lymphocytes may explain the lower incidence and severity of graft vs. host disease (GvHD) encountered in UCBT compared to the allogeneic transplant setting. Furthermore, UCB is rich in primitive CD16-CD56++ NK cells, which possess significant proliferative and cytotoxic capacities and can be expanded using IL-12 or IL-15, so as to mount a substantial graft vs. leukemia (GvL) effect. The major disadvantage of UCB is the low yield of stem cells, resulting in higher rates of engraftment failure and slower time to engraftment compared to bone marrow transplantation (BMT). A rational approach thus involves ex vivo expansion of UCB derived hematopoietic precursors. All these issues are discussed in detail in this review.
The basic domain of plant B-ZIP proteins facilitates import of a reporter protein into plant nuclei. (1991)

The import of large molecules into the nucleus is an active process that requires the presence in cis of a nuclear localization signal (NLS). Although these signals have been well characterized in mammalian, yeast, and amphibian nuclear proteins, no plant NLS has yet been described. The NLSs identified so far generally contain clusters of basic amino acids. This characteristic feature prompted us to test several basic domains from the plant DNA-binding proteins TGA-1A and TGA-1B and the TATA box-binding protein TFIID for nuclear targeting function. When tested as N-terminal fusions to the beta-glucuronidase protein, only those constructs containing the DNA binding (basic) domain of the basic-zipper (B-ZIP) region of TGA-1A or TGA-1B conferred nuclear import. These results suggest a close association or overlap of the DNA binding and nuclear targeting domains of B-ZIP proteins. We also demonstrated that a wild-type but not a mutant simian virus 40 large T-antigen NLS facilitates import into plant nuclei, indicating a strong conservation between nuclear import mechanisms in animals and plants.
Water Desalination across Nanoporous Graphene (2012)

We show that nanometer-scale pores in single-layer freestanding graphene can effectively filter NaCl salt from water. Using classical molecular dynamics, we report the desalination performance of such membranes as a function of pore size, chemical functionalization, and applied pressure. Our results indicate that the membrane's ability to prevent the salt passage depends critically on pore diameter with adequately sized pores allowing for water flow while blocking ions. Further, an investigation into the role of chemical functional groups bonded to the edges of graphene pores suggests that commonly occurring hydroxyl groups can roughly double the water flux thanks to their hydrophilic character. The increase in water flux comes at the expense of less consistent salt rejection performance, which we attribute to the ability of hydroxyl functional groups to substitute for water molecules in the hydration shell of the ions. Overall, our results indicate that the water permeability of this material is several orders of magnitude higher than conventional reverse osmosis membranes, and that nanoporous graphene may have a valuable role to play for water purification.
Gene delivery from replication-selective viruses: arming guided missiles in the war against cancer (2000)

Gene therapy aims to deliver therapeutic genetic material in a safe and efficient manner to a target tissue, where it can accumulate to levels that afford maximal patient benefit. Replication-defective viral vectors have been the workhorse of gene therapy for cancer and other conditions. These vectors allow the efficient delivery of a variety of transgenes to target tissues and have demonstrated clear therapeutic benefit and safety in a variety of preclinical neoplastic animal models. Unfortunately, the tremendous promise of studies using replication-defective viruses in preclinical models has not been translated into similar patient benefits in the clinical setting (1–3). This shortfall may be due in large part to the one-dimensional nature of these approaches, asking for a successful therapeutic outcome against a highly complex biological target like a human tumor through the activity of a single gene. Therapeutic gene delivery needs to develop into a multidimensional system if it is to be successful in treating human cancers. A natural evolution of gene therapy is its incorporation into replication-selective oncolytic viruses, combining the antitumor properties of the viral infection with the action of the therapeutic proteins.
A protective effect of L actobacillus rhamnosus HN 001 against eczema in the first 2 years of life persists to age 4 years (2012)

This study showed that the protective effect of HN001 against eczema, when given for the first 2 years of life only, extended to at least 4 years of age. This, together with our findings for a protective effect against rhinoconjunctivitis, suggests that this probiotic might be an appropriate preventative intervention for high risk infants.
Direct probing of the adsorbate-substrate chemical bond using angle-dependent x-ray-emission spectroscopy (1995)

Angle-dependent x-ray-emission spectroscopy is a method for studying adsorbed molecules, which makes it possible to directly probe the electronic states responsible for the surface chemical bond. This technique allows the separation of the adsorbate density of states both in terms of atomic site and orbital symmetry. This is demonstrated for CO adsorbed on Ni(100) and Cu(100). The occupied part of the 2\ensuremath{\pi}-3d adsorbate-substrate bond, projected on the C and O atoms, is observed directly.
Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor (2008)

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that controls plasma LDL cholesterol levels by posttranslational regulation of the LDL receptor (LDLR). Previously, we showed that PCSK9 binds specifically to an EGF-like repeat (EGF-A) in LDLR and reroutes the receptor from endosomes to lysosomes rather than to the cell surface. Here, we defined the regions in LDLR and PCSK9 that are required for receptor degradation and examined the relationship between PCSK9 binding and LDLR conformation. Addition of PCSK9 to cultured hepatocytes promoted degradation of WT LDLR and of receptors lacking up to four ligand binding domains, EGF-B or the clustered O-linked sugar region. In contrast, LDLRs lacking the entire ligand binding domain or the beta-propeller domain failed to be degraded, although they bound and internalized PCSK9. Using gel filtration chromatography, we assessed the effects of PCSK9 binding on an acid-dependent conformational change that happens in the extracellular domain of the LDLR. Although PCSK9 prevented the reduction in hydrodynamic radius of the receptor that occurs at a reduced pH, the effect was not sufficient for LDLR degradation. A truncated version of PCSK9 containing the prodomain and the catalytic domain, but not the C-terminal domain, bound the receptor but did not stimulate LDLR degradation. Thus, domains in both the LDLR and PCSK9 that are not required for binding (or internalization) are essential for PCSK9-mediated degradation of the LDLR.
Thermodynamic Additivity of Sequence Variations: An Algorithm for Creating High Affinity Peptides Without Large Libraries or Structural Information (2010)

By using this additivity algorithm, peptide ligands with high affinity for protein targets were generated. With this algorithm, one of the highest affinity TNF-α binding peptides reported to date was produced. Most importantly, high affinity was achieved from small, chemically-synthesized libraries without the need for structural information at any time during the process. This is significantly different than protein mutagenesis, directed evolution, or fragment-based design approaches, which rely on large libraries and/or structural guidance. With this algorithm, high affinity/specificity peptide ligands can be developed rapidly, inexpensively, and in an entirely chemical manner.
The spastic mouse. And the search for an animal model of spasticity in human beings. (1990)

An animal model of chronic spasticity would be valuable. There has been little success at producing such a model, however, because there is no frequently occurring natural disease in animals and, after experimental injury, the animals tend to die or recover. Spasticity in animals or humans is one of the many manifestations of an upper motor neuron syndrome; there is no such thing as pure spasticity. Spasticity in animals and humans involves abnormal functions at many levels of the neurologic and muscular systems. Animal models of spasticity may not be directly applicable to human spasticity, because the animal brain is so different from the human brain. Genetically spastic mice are a homogeneous population that have an abnormally functioning neurotransmitter within the central nervous system. This model has been shown to develop abnormalities of muscle growth that ultimately lead to contracture. The spastic mouse shows some promise for investigation of the abnormalities of muscles and joints that occur in spastic humans.
Genetic Markers, Map Construction, and Their Application in Plant Breeding (1996)

[...] The purpose of this paper is to describe available marker types and examine factors critical for their use in map construction and MAS [marker-assisted selection]. This review clarifies how genetic markers are used in map construction and defines the potential use of genetic maps for MAS [...]
Physiologically based pharmacokinetic modeling of 1,3-butadiene, 1,2- epoxy-3-butene, and 1,2:3,4-diepoxybutane toxicokinetics in mice and rats (1997)

1,3-Butadiene (BD) is a more potent tumor inducer in mice than in rats. BD also shows striking differences in metabolic activation, with substantially higher blood concentrations of 1,2:3,4-diepoxybutane (butadiene diepoxide; BDE) in BD-exposed mice than in similarly exposed rats. The objective of this study was to develop a single mechanistic model structure capable of describing BD disposition in both species. To achieve this objective, known pathways of 1,2-epoxy-3-butene (butadiene monoepoxide; BMO) and BDE metabolism were incorporated into a physiologically based pharmacokinetic model by scaling rates determined in vitro. With this model structure, epoxide clearance was underestimated for both rats and mice. Improved simulation of blood epoxide concentrations was achieved by addition of first-order metabolism in the slowly perfused tissues, verified by simulation of data on the time course for BMO elimination after i.v. injection of BMO. Blood concentrations of BD were accurately predicted for mice and rats exposed by inhalation to constant concentrations of BD. However, if all BD was assumed to be metabolized to BMO, blood concentrations of BMO were overpredicted. By assuming that only a fraction of BD metabolism produces BMO, blood concentrations of BMO could be predicted over a range of BD exposure concentrations for both species. In vitro and in vivo studies suggest an alternative cytochrome P-450-mediated pathway for BD metabolism that does not yield BMO. Including an alternative pathway for BD metabolism in the model also gave accurate predictions of blood BDE concentrations after inhalation of BD. Blood concentrations of BMO and BDE observed in both mice and rats are best explained by the existence of an alternative pathway for BD metabolism which does not produce BMO.
Exchange of recA protein between adjacent recA protein-single-stranded DNA complexes. (1986)

We have examined the exchange of recA protein between stable complexes formed with single-stranded DNA (ssDNA) and (a) other complexes and (b) a pool of free recA protein. We have also examined the relationship of ATP hydrolysis to these exchange reactions. Exchange was observed between two different recA X ssDNA complexes in the presence of ATP. Complete equilibration between two sets of complexes occurred with a t1/2 of 3-7 min under a set of conditions previously found to be optimal for recA protein-promoted DNA strand exchange. Approximately 200 ATPs were hydrolyzed for every detected migration of a recA monomer from one complex to another. This exchange occurred primarily between adjacent complexes, however. Little or no exchange was observed between recA X ssDNA complexes and the free recA protein pool, even after several hundred molecules of ATP had been hydrolyzed for every recA monomer present. ATP hydrolysis is not coupled to complete dissociation or association of recA protein from or with recA X ssDNA complexes under these conditions.
In Vitro Selection of RNA Aptamers to a Protein Target by Filter Immobilization (2000)

In vitro selection of RNA aptamers that bind to a protein target is detailed in the protocols presented in this unit. Aptamers generated from these types of selection experiments can potentially function as protein inhibitors, and are often used as diagnostic or therapeutic reagents.
Protection against lethal toxic shock by targeted disruption of the CD28 gene. (1996)

Toxic shock syndrome (TSS) is a multi system disorder resulting from superantigen-mediated cytokine production. Nearly 90% of the clinical cases of TSS arise due to an exotoxin, toxic shock syndrome toxin-1 (TSST-1), elaborated by toxigenic strains of Staphylococcus aureus. It is clearly established that besides antigen-specific signals a variety of costimulatory signals are required for full T cell activation. However, the nature and potential redundancy of costimulatory signals are incompletely understood, particularly with regards to superantigen-mediated T cell activation in vivo. Here we report that CD28-deficient mice (CD28-/-) are completely resistant to TSST-1-induced lethal TSS while CD28 (+/-) littermate mice were partially resistant to TSST-1. The mechanism for the resistance of the CD28 (-/-) mice was a complete abrogation of TNF-alpha accumulation in the serum and a nearly complete (90%) impairment of IFN-gamma secretion in response to TSST-1 injection. In contrast, the serum level of IL-2 was only moderately influenced by the variation of CD28 expression. CD28 (-/-) mice retained sensitivity to TNF-alpha as demonstrated by equivalent lethality after cytokine injection. These findings establish an essential requirement for CD28 costimulatory signals in TSST-1-induced TSS. The hierarchy of TSST-1 resistance among CD28 wild-type (CD28+/+), CD28 heterozygous (CD28+/-), and CD28-/- mice suggests a gene-dose effect, implying that the levels of T cell surface CD28 expression critically regulate superantigen-mediated costimulation. Finally, as these results demonstrate the primary and non-redundant role of CD28 receptors in the initiation of the in vivo cytokine cascade, they suggest therapeutic approaches for superantigen-mediated immunopathology.