gebhart/patrepeval huggingface dataset:
Insulin stimulates the activity of a novel protein kinase C, PKC-epsilon, in cultured fetal chick neurons. (1990)

In this study we examined the effects of insulin on protein kinase C (PKC) activity in cultured fetal chick neurons. PKC activity, measured as 32P incorporation into histone H1 in the presence of calcium (500 microM), phosphatidylserine (100 micrograms/ml), and diolein (3.3 micrograms/ml) minus the incorporation in the presence of calcium alone, was detected in neuronal cytosolic (207 +/- 33 pmol/min/mg) and membrane (33 +/- 8 pmol/min/mg) fractions. Insulin added to intact neurons increased the activity of PKC in both cytosolic and membrane fractions by about 40%. Neurons preincubated with cycloheximide (10 micrograms/ml) 30 min prior to insulin treatment showed the same degree of stimulation of PKC activity by insulin. The activation of PKC was maximal within 5-10 min of insulin exposure and was sustained for at least 60 min. Insulin stimulated PKC in a dose-dependent manner, with a maximal response obtained at 100 ng/ml. Addition of phosphatidylserine and diolein to neuronal cell extracts resulted in the phosphorylation of four major cytosolic proteins (70, 57, 18, and 16 kDa) and one major membrane protein (75 kDa). Phosphorylation of all five proteins was increased 2-fold in extracts from insulin-treated neurons. Immunoblot analysis of whole cell extracts using antibodies against PKC-alpha, PKC-beta, PKC-gamma, PKC-delta, and PKC-epsilon revealed that cultured fetal chick neurons contained only one of these PKC isoforms, the epsilon-isoform. The enzyme was mostly cytosolic. Insulin had no effect on either the amount of distribution of PKC-epsilon in cultured neurons but induced a small change in the mobility of PKC-epsilon on sodium dodecyl sulfate-polyacrylamide gels. When assay conditions were designed to measure specifically the activity of PKC-epsilon, using a synthetic peptide substrate in the absence of calcium, activity was 50 +/- 12% higher in insulin-treated cells (p less than 0.005). PKC activity in control and insulin treated-neurons was almost completely inhibited when assays included a peptide identical to the pseudo-substrate binding site of PKC-epsilon. We conclude that PKC-epsilon is the major PKC isoform present in cultured fetal chick neurons. Insulin stimulates PKC-epsilon activity by a mechanism that does not involve translocation of the enzyme from cytosol to membrane.
The Columbia–Suicide Severity Rating Scale: Initial Validity and Internal Consistency Findings From Three Multisite Studies With Adolescents and Adults (2011)

These findings suggest that the C-SSRS is suitable for assessment of suicidal ideation and behavior in clinical and research settings.
Structure-Based Design of Potent Non-Peptide MDM2 Inhibitors (2005)

A successful structure-based design of a class of non-peptide small-molecule MDM2 inhibitors targeting the p53-MDM2 protein-protein interaction is reported. The most potent compound 1d binds to MDM2 protein with a Ki value of 86 nM and is 18 times more potent than a natural p53 peptide (residues 16-27). Compound 1d is potent in inhibition of cell growth in LNCaP prostate cancer cells with wild-type p53 and shows only a weak activity in PC-3 prostate cancer cells with a deleted p53. Importantly, 1d has a minimal toxicity to normal prostate epithelial cells. Our studies provide a convincing example that structure-based strategy can be employed to design highly potent, non-peptide, cell-permeable, small-molecule inhibitors to target protein-protein interaction, which remains a very challenging area in chemical biology and drug design.
Lasers and mass spectrometry (1991)

C.H. Chen et al : Isotopically selective counting of atoms and molecules using resonance ionization spectroscopy J.E. Parks: Surface analysis using resonance ionization spectroscopy C.H. Becker: The analysis of inorganic and organic surfaces by ionization of desorbed neutrals with untuned ultraviolet and vacuum ultraviolet lasers N.S. Nogar & R.C. Estler: Laser desorption/laser ablation with detection by resonance ionization mass spectrometry R.W. Odom & B. Schueler: Laser microprobe mass spectrometry J.J. Morelli: Laser micro mass spectrometry for direct analysis of coal macerals D.P. Land t al: Post-ionization of laser-desorbed neutrals for the analysis of molecular adsorbates on surfaces P. Arrowsmith: Applications of laser ablation K.R. Hess & W.W. Harrison: Laser ablation and ionization studies in a glow discharge W. Emary et al: Lasers for the generation and excitation of ions in tandem mass spectrometry R.R. Weller et al: Combining lasers with Fourier transform ion cyclotron resonance mass spectrometry M.P. Chiarelli & M.L. Gross: Lasers and Fourier transform mass spectrometry L.M. Nuwaysir & C.L. Wilkins: Lasers coupled with Fourier transform mass spectrometry R.B. Cody et al : Applications of laser desorption/Fourier transform mass spectrometry to polymer and surface analysis J. Shabanowitz & D.F. Hunt: Laser photodissociation on a tandem quadrupole Fourier-transform mass spectrometer D.M. Lubman & L. Li: Resonant two-photon ionization spectroscopy of biological molecules in supersonic jets volatilized by pulsed laser desorption M.S. de Vries et al: Analysis of organic molecules on surfaces T.R. Rizzo & D.H. Levy: Multiphoton ionization spectroscopy of biologically related molecules in supersonic molecular beam J.W. Hager & S.C. Wallace: Two-colour threshold photoionization spectroscopy of polyatomic molecules and clusters T.A. Cool: Combustion species detection by resonance enhanced ionization J.A. Syage: New developments in molecular detection by supersonic molecular beam, laser mass spectrometry R.B. Opsal: Resolution and sensitivity in laser ionization mass spectrometry S. Weeks et al: Multidimension, resonance enhanced multiphoton ionization time-of-flight mass spectrometry for characterizing environmental and biological samples for polycyclic aromatic compounds.
Novel Cancer Antiangiotherapy Using the VEGF Promoter-targeted Artificial Zinc-finger Protein and Oncolytic Adenovirus (2008)

Inhibition of tumor angiogenesis through modulation of vascular endothelial growth factor (VEGF) and its signaling pathway has been clinically validated as a viable therapeutic modality in the treatment of cancer. The use of artificial transcription factors based on Cys2-His2 zinc-finger proteins (ZFPs) targeting the VEGF promoter offers a novel strategy for modulating VEGF levels in tumors. In order to demonstrate the utility of VEGF-targeted ZFPs as therapeutic agents, we generated adenoviruses (Ads) expressing VEGF promoter-targeted transcriptional repressor ZFP, F435-KOX. A replication-incompetent Ad expressing F435-KO X, namely, Ad-DeltaE1-KOX, significantly reduced VEGF expression and functionally led to inhibition of angiogenesis. In vivo, an oncolytic Ad expressing F435-KOX, namely, Ad-DeltaB7-KOX, elicited a pronounced antitumor effect against a human glioblastoma xenograft model, U87MG. Further, consistent with its expected mechanism of action, Ad-DeltaB7-KOX was shown to greatly reduce the level of VEGF and vessel density in tumor tissue and increase terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive apoptotic cells in tumors. Survival rates were also significantly increased in Ad-DeltaB7-KOX-treated mice. Taken together, the findings from this study identify F435-KOX as a novel and potent ZFP transcription factor that can inhibit VEGF-A-mediated angiogenesis and offer a novel therapeutic modality in the treatment of cancer.
2-deoxygalactose, a specific substrate of the Salmonella typhiimurium galactose permease: its use for the isolation of galP mutants (1978)

2-Deoxygalactose is a specific substrate of the galactose permease. The apparent Km is about 500 micron, compared to 45 micron for galactose, whereas the maximal rate of uptake is one-half to one-third of that of galactose. None of the other galactose transport systems, including methyl beta-D-thiogalactosides I and II, the beta-methyl-galactoside permease, and both arabinose systems, is able to catalyze transport of 2-deoxygalactose to a significant extent. 2-Deoxygalactose can also be used to isolate mutants defective in galactose permease, since it is bacteriostatic. Colonies that grow with lactate, malate, or succinate as a carbon source in the presence of 0.5 to 2 mM 2-doexygalactose were found to be mostly galP mutants, lacking galactose permease. Spontaneous 2-deoxygalactose-resistant strains arose with a frequency of about 2 X 10(-6). galP mutants have also been derived from pts deletion mutants that require galactose permease for growth on glucose. Revertants have been obtained that have acquired the parental phenotype.
Four glucosyltransferases, GtfJ, GtfK, GtfL and GtfM, from Streptococcus salivarius ATCC 25975 (1995)

The four recombinant glucosyltransferases (GTFs), GtfJ, GtfK, GtfL and GtfM, that had previously been cloned from Streptococcus salivarius ATCC 25975, were individually expressed in Escherichia coli and their glucan products and kinetic properties were analysed. GtfJ was a primer-dependent GTF which synthesized an insoluble glucan composed mainly of alpha-(1-->3)-linked glucosyl residues in the presence of dextran T-10. GtfK was primer-stimulated, and produced a linear soluble dextran without any detectable branch points both in the absence and in the presence of dextran T-10. GtfL was primer-independent and produced a mixed-linkage insoluble glucan composed of approximately equal proportions of alpha-(1-->3)- and alpha-(1-->6)-linked glucosyl residues. GtfL was inhibited by dextran T-10. GtfM was primer-independent and produced a soluble dextran with approximately 5% alpha-(1-->3)-linked glucosyl residues. GtfM was essentially unaffected by the presence of dextran T-10. The results confirmed that each enzyme represented one of the four possible combinations of primer-dependency and product solubility and that each possessed unique biosynthetic properties. The soluble dextrans formed by GtfK and GtfM, as well as the mixed-linkage insoluble glucan formed by GtfL, were also capable of acting as primers for the primer-dependent GtfJ and the primer-stimulated GtfK. Unexpectedly, the linear dextran produced by GtfK was by far the least effective either at priming itself or at activating and priming the primer-dependent GtfJ.
Pharmacologic Therapy: Novel Approaches for Chronic Obstructive Pulmonary Disease (2007)

Chronic obstructive pulmonary disease (COPD) is increasing in the United States and throughout the world. There have been a number of advances in the treatment of this disease within the last several decades, and these improved therapies continue to become available, making the prospects for the future encouraging. Bronchodilation is the treatment of choice, and we point out in this article the potential availability of many new bronchodilators. There will be several options in the beta(2)-agonist and the anticholinergic categories for once-a-day preparations. There will also be a number of products combining these categories of bronchodilators and inhaled steroids, and the combination products will be available in once-a-day preparations. Also under development are several candidates for specific and effective antiinflammatory agents in COPD. It is likely that our ability to control the inflammation underlying COPD will be a reality in the future. Although many new cases of COPD are being diagnosed in former smokers, for patients who smoke, the most important treatment is smoking cessation. A number of new drugs are available, and more will be brought to market in the future. We have highlighted the details of this important area.
Stable Amorphous CaCO3 Microparticles with Hollow Spherical Superstructures Stabilized by Phytic Acid (2005)

Amorphous CaCO3 (ACC) is stabilized by the presence of phytic acid, a natural inositol hexakisphosphate (IP6). Micrometer-sized hollow spheres of ACC have been obtained (see Figure). The spheres are stable for at least three months in solution, which is equivalent to that described for more complex special biopolymers in biomineralization processes, and by far exceeds the previously known stability of ACC prepared in the presence of synthetic molecules. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2089/2005/c0747_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.
Quantitative Analysis of the Coverage Density of Br– Ions on Pd{100} Facets and Its Role in Controlling the Shape of Pd Nanocrystals (2013)

We report an approach based on a combination of inductively coupled plasma mass spectrometry and X-ray photoelectron spectroscopy for quantitative analysis of the role played by Br(-) ions in the synthesis of Pd nanocrystals. The Br(-) ions were found to adsorb onto Pd{100} facets selectively with a coverage density of ca. 0.8 ion per surface Pd atom. The chemisorbed Br(-) ions could be removed via desorption at an elevated temperature under reductive conditions. They could also be gradually released from the surface when Pd cubic seeds grew into cuboctahedrons and then octahedrons. On the basis of the coverage density information, we were able to estimate the minimum concentration of Br(-) ions needed for the formation of Pd nanocubes with a specific size. If the concentration of Br(-) ions was below this minimum value, not all of the {100} facets could be stabilized by the capping agent, leading to the formation of nanocubes with truncated corners. The quantitative analysis developed in this study is potentially extendable to other systems involving chemisorbed capping agents.
A Cereblon Modulator (CC-220) with Improved Degradation of Ikaros and Aiolos (2017)

The drugs lenalidomide and pomalidomide bind to the protein cereblon, directing the CRL4-CRBN E3 ligase toward the transcription factors Ikaros and Aiolos to cause their ubiquitination and degradation. Here we describe CC-220 (compound 6), a cereblon modulator in clinical development for systemic lupus erythematosis and relapsed/refractory multiple myeloma. Compound 6 binds cereblon with a higher affinity than lenalidomide or pomalidomide. Consistent with this, the cellular degradation of Ikaros and Aiolos is more potent and the extent of substrate depletion is greater. The crystal structure of cereblon in complex with DDB1 and compound 6 reveals that the increase in potency correlates with increased contacts between compound 6 and cereblon away from the modeled binding site for Ikaros/Aiolos. These results describe a new cereblon modulator which achieves greater substrate degradation via tighter binding to the cereblon E3 ligase and provides an example of the effect of E3 ligase binding affinity with relevance to other drug discovery efforts in targeted protein degradation.
Clinical and economic outcomes after surgical aortic valve replacement in Medicare patients (2012)

Among elderly patients undergoing AVR, long-term mortality and costs are substantially greater for high-risk than for non-high-risk individuals. These findings indicate that further research is needed to understand whether newer approaches to aortic valve replacement such as transcatheter AVR may be a lower cost, clinically valuable alternative.
The concurrency workbench (1993)

The Concurrency Workbench is an automated tool for analyzing networks of finite-state processes expressed in Milner's Calculus of Communicating Systems. Its key feature is its breadth: a variety of different verification methods, including equivalence checking, preorder checking, and model checking, are supported for several different process semantics. One experience from our work is that a large number of interesting verification methods can be formulated as combinations of a small number of primitive algorithms. The Workbench has been applied to the verification of communications protocols and mutual exclusion algorithms and has proven a valuable aid in teaching and research.
XopC and XopJ, Two Novel Type III Effector Proteinsfrom Xanthomonas campestris pv.vesicatoria (2003)

Pathogenicity of the gram-negative plant pathogen Xanthomonas campestris pv. vesicatoria depends on a type III secretion (TTS) system which translocates bacterial effector proteins into the plant cell. Previous transcriptome analysis identified a genome-wide regulon of putative virulence genes that are coexpressed with the TTS system. In this study, we characterized two of these genes, xopC and xopJ. Both genes encode Xanthomonas outer proteins (Xops) that were shown to be secreted by the TTS system. In addition, type III-dependent translocation of both proteins into the plant cell was demonstrated using the AvrBs3 effector domain as a reporter. XopJ belongs to the AvrRxv/YopJ family of effector proteins from plant and animal pathogenic bacteria. By contrast, XopC does not share significant homology to proteins in the database. Sequence analysis revealed that the xopC locus contains several features that are reminiscent of pathogenicity islands. Interestingly, the xopC region is flanked by 62-bp inverted repeats that are also associated with members of the Xanthomonas avrBs3 effector family. Besides xopC, a second gene of the locus, designated hpaJ, was shown to be coexpressed with the TTS system. hpaJ encodes a protein with similarity to transglycosylases and to the Pseudomonas syringae pv. maculicola protein HopPmaG. HpaJ secretion and translocation by the X. campestris pv. vesicatoria TTS system was not detectable, which is consistent with its predicted Sec signal and a putative function as transglycosylase in the bacterial periplasm.
Novel somatic mutations of the MET oncogene in human carcinoma metastases activating cell motility and invasion. (2002)

Several gene mutations responsible for human cancer initiation have been discovered, whereas only a few have been identified in association with the progression to metastasis. In this study, we screened a large panel of human sporadic cancers, metastases, and tumor cell lines for mutations in the tyrosine kinase domain of the MET receptor, crucially involved in invasive cell growth and motility during embryogenesis. MET activating mutations have been described previously in hereditary papillary renal cell carcinoma and in a few sporadic tumors. Summarizing results of this and our previous studies, we did not detect mutations in the MET kinase domain from 153 sporadic human cancers and 25 cancer cell lines, whereas we found somatic MET mutations in 10 of 46 lymph nodal and 2 of 14 pulmonary metastases. We identified four MET mutations in metastases. Two were known as MET germ-line mutations (H1112R and Y1248C), which predispose to hereditary renal cell carcinoma. One of the two novel mutations (N1118Y) changed an asparagine in the region of the glycine-rich ATP binding site, which is highly conserved in all of the kinases. The other (Y1253D) changed a critical tyrosine, known to regulate MET kinase activity, to a negatively charged residue. The MET receptors carrying either the N1118Y or the Y1253D mutation were constitutively active and conferred a motile-invasive phenotype on transduced carcinoma cells. The latter phenotype was additionally stimulated by the MET receptor ligand scatter factor/hepatocyte growth factor. These data suggest that MET might be one of the long sought oncogenes controlling progression of primary cancers to metastasis.
An Approach to Estimate Between- and Within-Group Correlation Coefficients in Multicenter Studies: Plasma Carotenoids as Biomarkers of Intake of Fruits and Vegetables (2005)

In a multicenter study, the overall correlation between two variables can be broken down into a within- and a between-group correlation reflecting associations at the individual and aggregate levels, respectively. A random-effects model is used to estimate variance components of nutrition-related variables and the within- and between-group correlation coefficients. Using data from the European Prospective Investigation into Cancer and Nutrition (EPIC), the authors analyzed the association between levels of three plasma carotenoids (alpha-carotene, beta-cryptoxanthin, and lycopene) and dietary intake of three items (total fruits, carrots, and tomatoes), assessed through dietary questionnaire and single 24-hour dietary recall measurements, in a cross-sectional study involving 3,089 subjects from nine European countries. Intraclass correlation coefficients were 0.178 for alpha-carotene, 0.216 for beta-cryptoxanthin, and 0.299 for lycopene. The between-group correlation coefficients were higher than the within-group coefficients for all three carotenoids. For beta-cryptoxanthin and fruit intake, the between-group versus the within-group correlations were 0.78 and 0.26 for the dietary questionnaire and 0.85 and 0.19 for the 24-hour dietary recall. Results indicate that variability of exposure is driven mainly by the individual compared with the aggregate variation and that biomarker levels perform fairly accurately in discriminating population-level consumption of fruits and vegetables.
[Diagnosis of Alzheimer's disease. Evaluation of senile plaques of the diffuse type]. (1992)

The different types of plaques throughout the thickness of the pole of the temporal lobule of brains from autopsies of a patient with Alzheimer's disease and two elderly patients with normal cognitive function were quantified. Thioflavin-S techniques and cholinesterase marking indicating amyloid aggregates were employed. If the Khachaturian criteria had been followed one of the controls would have also been diagnosed with involvement of Alzheimer's disease. The aforementioned control and patients with Alzheimer's disease had numerous senile plaques, most of which were diffuse, however, only the patient with senile dementia also had neuritic plaques. This fact indicates the convenience of reviewing the pathologic diagnosis of Alzheimer's disease in two ways: firstly, specific techniques for neurofibrillary degeneration should be included and secondly, the plaques with neurofibrillary degeneration should be quantified since diffuse plaques without degeneration appear to have a questionable significance with respect to this diagnosis.
Expression of the Ryanodine Receptor Isoforms in Immune Cells (2001)

Ryanodine receptor (RYR) is a Ca(2+) channel that mediates Ca(2+) release from intracellular stores. We have used RT-PCR analysis and examined its expression in primary peripheral mononuclear cells (PBMCs) and in 164 hemopoietic cell lines. In PBMCs, type 1 RYR (RYR1) was expressed in CD19(+) B lymphocytes, but less frequently in CD3(+) T lymphocytes and in CD14(+) monocytes. Type 2 RYR (RYR2) was mainly detected in CD3(+) T cells. Induction of RYR1 and/or RYR2 mRNA was found after treatment with stromal cell-derived factor 1, macrophage-inflammatory protein-1alpha (MIP1alpha) or TGF-beta. Type 3 RYR (RYR3) was not detected in PBMCs. Many hemopoietic cell lines expressed not only RYR1 or RYR2 but also RYR3. The expression of the isoforms was not associated with specific cell lineage. We showed that the RYR-stimulating agent 4-chloro-m-cresol (4CmC) induced Ca(2+) release and thereby confirmed functional expression of the RYR in the cell lines expressing RYR mRNA. Moreover, concordant induction of RYR mRNA with Ca(2+) channel function was found in Jurkat T cells. In untreated Jurkat T cells, 4CmC (>1 mM) had no effect on Ca(2+) release, whereas 4CmC (<400 microM) caused Ca(2+) release after the induction of RYR2 and RYR3 that occurred after treatment with stromal cell-derived factor 1, macrophage-inflammatory protein-1alpha, or TGF-beta. Our results demonstrate expression of all three isoforms of RYR mRNA in hemopoietic cells. Induction of RYRs in response to chemokines and TGF-beta suggests roles in regulating Ca(2+)-mediated cellular responses during the immune response.