gebhart/patrepeval huggingface dataset:
Zmpste24 deficiency in mice causes spontaneous bone fractures, muscle weakness, and a prelamin A processing defect (2002)

Zmpste24 is an integral membrane metalloproteinase of the endoplasmic reticulum. Biochemical studies of tissues from Zmpste24-deficient mice (Zmpste24(-/-)) have indicated a role for Zmpste24 in the processing of CAAX-type prenylated proteins. Here, we report the pathologic consequences of Zmpste24 deficiency in mice. Zmpste24(-/-) mice gain weight slowly, appear malnourished, and exhibit progressive hair loss. The most striking pathologic phenotype is multiple spontaneous bone fractures-akin to those occurring in mouse models of osteogenesis imperfecta. Cortical and trabecular bone volumes are significantly reduced in Zmpste24(-/-) mice. Zmpste24(-/-) mice also manifested muscle weakness in the lower and upper extremities, resembling mice lacking the farnesylated CAAX protein prelamin A. Prelamin A processing was defective both in fibroblasts lacking Zmpste24 and in fibroblasts lacking the CAAX carboxyl methyltransferase Icmt but was normal in fibroblasts lacking the CAAX endoprotease Rce1. Muscle weakness in Zmpste24(-/-) mice can be reasonably ascribed to defective processing of prelamin A, but the brittle bone phenotype suggests a broader role for Zmpste24 in mammalian biology.
Sequential Tyrosine Sulfation of CXCR4 by Tyrosylprotein Sulfotransferases (2008)

CXC-chemokine receptor 4 (CXCR4) is a G protein-coupled receptor for stromal cell-derived factor-1 (SDF-1/CXCL12). SDF-1-induced CXCR4 signaling is indispensable for embryonic development and crucial for immune cell homing and has been implicated in metastasis of numerous types of cancer. CXCR4 also serves as the major coreceptor for cellular entry of T-cell line-tropic (X4) HIV-1 strains. Tyrosine residues in the N-terminal tail of CXCR4, which are post-translationally sulfated, are implicated in the high-affinity binding of SDF-1 to CXCR4. However, the specific roles of three potential tyrosine sulfation sites are not well understood. We investigated the pattern and sequence of CXCR4 sulfation by using recombinant human tyrosylprotein sulfotransferases TPST-1 and TPST-2 to modify a peptide that corresponds to amino acids 1-38 of the receptor (CXCR4 1-38). We analyzed the reaction products with a combination of reversed-phase HPLC, proteolytic cleavage, and mass spectrometry. We found that CXCR4 1-38 is sulfated efficiently by both TPST enzymes, leading to a final product with three sulfotyrosine residues. Sulfates were added stepwise to the peptide, producing specific intermediates with one or two sulfotyrosines. The pattern of sulfation in these intermediates indicates that with both enzymes Tyr-21 is sulfated first, followed by Tyr-12 or Tyr-7. Using heteronuclear NMR spectroscopy, we demonstrated that the SDF-1 binding affinity of CXCR4 1-38 increases with the number of sulfotyrosines present, which suggests a potential physiological role for sulfation of all three sites in the N-terminus of CXCR4. These results provide a structural basis for understanding the role of post-translational tyrosine sulfation in SDF-1-induced CXCR4 signaling.
Targeting the epidermal growth factor receptor in non-small cell lung cancer. (2003)

Fifteen% or fewer of patients with non-small cell lung cancer (NSCLC) survive 5 years. The current standard of care for patients with locally advanced or metastatic NSCLC is systemic chemotherapy with a two-drug combination regimen that includes a platinum agent. Although systemic chemotherapy reduces the rate of death attributable to lung cancer, disease progression is inevitable and dose-limiting toxicities restrict their use. New molecularly targeted therapies aim to inhibit specific pathways and key molecules implicated in tumor growth and progression while sparing normal cells. Several therapies, which target signal transduction pathways involved in angiogenesis, metastasis, and apoptosis, are in clinical development to treat lung cancer. Among these targeted therapies are the oral, small-molecule epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitors gefitinib and erlotinib. Both therapies have been validated preclinically as new treatment approaches for NSCLC and have shown single-agent activity against advanced, chemorefractory NSCLC in clinical trials. This article focuses on the biology of the EGFR-TK signal transduction pathway, its role in the proliferation of solid tumors, and the rationale for the clinical development of EGFR-TK inhibitors. We also review clinical trials with EGFR-TK inhibitors in NSCLC and future directions of investigation with these targeted agents.
Diverse Viewpoints on Computational Aspects of Molecular Diversity (2001)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTDiverse Viewpoints on Computational Aspects of Molecular DiversityYvonne C. MartinView Author Information Computer Assisted Molecular Design, Abbott Laboratories, Abbott Park, Illinois 60064-3500 Cite this: J. Comb. Chem. 2001, 3, 3, 231–250Publication Date (Web):March 8, 2001Publication History Received25 August 2000Published online8 March 2001Published inissue 1 May 2001https://pubs.acs.org/doi/10.1021/cc000073ehttps://doi.org/10.1021/cc000073ereview-articleACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views587Altmetric-Citations69LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options SUBJECTS:Cluster chemistry,Combinatorial libraries,Drug discovery,Molecules,Pharmacophores Get e-Alerts
A Structural View of the Action ofEscherichia coli(lacZ) β-Galactosidase, (2001)

The structures of a series of complexes designed to mimic intermediates along the reaction coordinate for beta-galactosidase are presented. These complexes clarify and enhance previous proposals regarding the catalytic mechanism. The nucleophile, Glu537, is seen to covalently bind to the galactosyl moiety. Of the two potential acids, Mg(2+) and Glu461, the latter is in better position to directly assist in leaving group departure, suggesting that the metal ion acts in a secondary role. A sodium ion plays a part in substrate binding by directly ligating the galactosyl 6-hydroxyl. The proposed reaction coordinate involves the movement of the galactosyl moiety deep into the active site pocket. For those ligands that do bind deeply there is an associated conformational change in which residues within loop 794-804 move up to 10 A closer to the site of binding. In some cases this can be inhibited by the binding of additional ligands. The resulting restricted access to the intermediate helps to explain why allolactose, the natural inducer for the lac operon, is the preferred product of transglycosylation.
General Ligand Affinity Chromatography in Enzyme Purification Ligands, Affinity Chromatography, Enzyme Purification (1976)

Abstract Recent developments in enzyme purification have revolutionized isolation techniques and at the same time provided a more profitable manner in which to obtain them. These developments are primarily concerned with the preparation and usability of imobilized ligands for the selective isolation and purification of biologically active substance1–5, particularly enzymes. This technique is based on the unique principle that the biological macromolecule is able to be adsorbed to the immobilized ligand, specifically and reversibly, unlike the traditional methods by which proteins are separated by their dffferences in physicochemical properties. Numerous proteins have been purified since this technique was first applied by Campbell et al.6 for the purification and isolation of antibodies. From these preliminary efforts it is apparent that further development of thfs method would greatly facilitate our understanding and utilizattion of enzymes.
An Iterative CT Reconstruction Algorithm for Fast Fluid Flow Imaging (2015)

The study of fluid flow through solid matter by computed tomography (CT) imaging has many applications, ranging from petroleum and aquifer engineering to biomedical, manufacturing, and environmental research. To avoid motion artifacts, current experiments are often limited to slow fluid flow dynamics. This severely limits the applicability of the technique. In this paper, a new iterative CT reconstruction algorithm for improved a temporal/spatial resolution in the imaging of fluid flow through solid matter is introduced. The proposed algorithm exploits prior knowledge in two ways. First, the time-varying object is assumed to consist of stationary (the solid matter) and dynamic regions (the fluid flow). Second, the attenuation curve of a particular voxel in the dynamic region is modeled by a piecewise constant function over time, which is in accordance with the actual advancing fluid/air boundary. Quantitative and qualitative results on different simulation experiments and a real neutron tomography data set show that, in comparison with the state-of-the-art algorithms, the proposed algorithm allows reconstruction from substantially fewer projections per rotation without image quality loss. Therefore, the temporal resolution can be substantially increased, and thus fluid flow experiments with faster dynamics can be performed.
A study on a channel allocation scheme with an adaptive array in SDMA (2002)

This paper describes spatial division multiple access (SDMA) using an adaptive array. A spatial correlation coefficient is proposed as a criterion to determine the possibility of duplicate channel allocation. When the average input SNR is more than 20 dB, the users satisfying a correlation coefficient of less than 0.9 can be accommodated in the same channel in a 2-user SDMA model with a 2-element adaptive array. The blocking rate performance shows that this 2-user SDMA can improve channel efficiency almost twice.
Treatment of refractory inflammatory monoarthritis in ankylosing spondylitis by intraarticular injection of infliximab. (2006)

We observed a beneficial effect of IA infliximab in refractory arthritis in patients with AS. This procedure could be considered an effective and safe treatment for therapy of refractory monoarthritis in AS and an alternative for parenteral TNF-blocking therapy.
Multiple Eruptive Melius Hair Cysts Treated with Carbon Dioxide Laser Vaporization (1987)

The use of carbon dioxide laser to treat multiple facial, eruptive vellus hair cysts is described. An excellent cosmetic result without scarring or recurrence of lesions was obtained.
Two Cases of Acneiform Eruption Induced by Inhibitor of Epidermal Growth Factor Receptor (2007)

The cutaneous adverse effects of cetuximab are similar to other EGF-R-targeted agents and result from direct interference with the functions of EGF-R signaling in the skin.
Differential effects of W mutations on p145c-kit tyrosine kinase activity and substrate interaction. (1992)

The c-kit gene, mapped to the dominant white spotting (W) locus of the mouse (Chabot, B., Stephenson, D. A., Chapman, V. M., Besmer, P., and Bernstein, A. (1988) Nature 335, 88-89; Geissler, E. N., Ryan, M. A., and Housman, D. E. (1988) Cell 55, 185-192), encodes a receptor tyrosine kinase, p145c-kit. Germline mutations at the W locus lead to loss of function alterations in p145c-kit, and result in mice with developmental defects of varying severity in the melanocytic, hematopoietic stem cell, and primordial germ cell lineages. To investigate in more detail the effect of W mutations on p145c-kit signaling, three mutations, W42, Wv, and W41, that confer severe, intermediate, and mild phenotypic characteristics, respectively, were introduced into the human p145c-kit tyrosine kinase domain. These mutations attenuated the intrinsic tyrosine kinase activity of the receptor to different degrees. In addition, they had differential effects on the interaction of the p145c-kit substrates, phospholipase C gamma, GTPase-activating protein, and the receptor-binding subunit of phosphatidylinositol 3'-kinase, p85. Notably, the Wv mutation, while retaining significant receptor tyrosine kinase activity, was unable to bind phospholipase C gamma and GTPase-activating protein, but could still associate with p85. These results suggest that the location of W mutations may be an important determinant of the specificity of substrate association and phosphorylation, and may explain, at least in part, the cell type-specific defects associated with certain W alleles.
CLINICAL SIGNIFICANCE OF MEASUREMENT OF UROKINASE-TYPE PLASMINOGEN ACTIVATOR ANTIGEN IN PLASMA (1993)

The plasma concentration of urokinase-type plasminogen activator (u-PA) antigen in 107 cases of various diseases associated with angiopathy and thrombosis was measured with ELISA method. The plasma level of u-PA antigen showed a tendency to increase in diabetes mellitus, hypertension, acute cerebral and myocardial infarctions when compared with that of normal control. The significant elevation of u-PA levels was found in coronary heart disease, deep venous thrombosis, varicosis and arterial occlusion (P<0.001) . These results suggested that measurment of plasma u-PA antigen could be a reference parameter for evaluating the functioning situation of in vivo endothelial cells.


Key words: 
Urokinase-type plasminogen activator; acute cerebral infarction; acute myocardial infarction.
Quantitative Approach to Single-Nucleotide Polymorphism Analysis Using MALDI-TOF Mass Spectrometry (2000)

Pooling of DNA samples before genotyping is a valuable means of streamlining large-scale genotyping efforts in disease association studies, single-nucleotide polymorphism (SNP) validation or mutant allele screening programs. In this report, we explore the application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to quantitative analysis of SNPs. The measurements are based on MALDI-TOF MS analysis of primer extension assays performed on standard mixtures of pooled PCR products at several test loci. The inherent high molecular weight resolution of MALDI-TOF MS conveys high specificity and good signal-to-noise ratio for performing accurate quantitation. The methods described maximize the sensitivity and quantitative capacity of MALDI-TOF MS while preserving the throughput and economic advantages of the MALDI-TOF platform. Using the format described, we demonstrate that allele frequencies as low as 5% can be detected quantitatively and unambiguously.
Perovskites by Design:  A Toolbox of Solid-State Reactions (2002)

In recent years, many soft-chemical reactions of layered perovskites have been reported, and they can be classified into sets of similar reactions. Simple ion-exchange and intercalation reactions replace or modify the interlayer cations of layered perovskites, and more complex metathesis reactions replace interlayer cations with cationic structural units. Topochemical condensation reactions that involve dehydration and reduction provide access to a variety of metastable structural features in three-dimensional perovskites, and similar reactions can be used to convert among higher order layered perovskite homologues. Other techniques, such as high pressure and anion intercalation/deintercalation, also yield interesting metastable phases. When combined, the individual reactions complement each other, and a powerful toolbox of solid-state reactions emerges. By using layered perovskites as templates, it is possible to retrosynthetically design new product perovskites that retain the structural features of the precursor layered phases. The toolbox of reactions was used to synthesize a new Ruddlesden−Popper phase, Na2Sr2Nb2MnO10, and to demonstrate the first example of a complete cycle of reactions of layered perovskites. In addition, topochemical dehydration and reduction were combined to synthesize the new A-site defective cubic perovskite Ca0.67Eu1.33La0.67Ti3O9. It should be possible to extend the toolbox to include more complex systems using layer-by-layer assembly of perovskite thin films, which provide access to “made to order” stacking sequences.
Clonal analysis of sucrase-isomaltase expression in the human colon adenocarcinoma Caco-2 cells (1991)

To investigate the biosynthetic basis for the mosaic expression of brush border enzymes in confluent Caco-2 cells, a human colon carcinoma cell line exhibiting characteristics of adult small intestinal enterocytes, we have obtained a series of clones differing markedly in their growth rates, amounts of transforming growth factor-alpha/epidermal growth factor-like activity released into the culture medium, and sucrase-isomaltase (SI) activity. Other intestinal markers (aminopeptidase N, dipeptidylpeptidase IV, lactase, alkaline phosphatase and 'crypt cell antigen') displayed a much more limited variability in expression, suggesting that the Caco-2 cell clones we have obtained did not differ in their overall ability to differentiate. Immunofluorescence staining, metabolic labelling with radioactive methionine and hybridization analysis of SI mRNA abundance were used to investigate SI synthesis and its regulation in clones endowed with low, intermediate or high sucrase activity. The results obtained have demonstrated heterogeneous SI expression, even in clonal cell lines, and a negative correlation between SI expression and growth factor concentrations in the culture medium, suggesting an autocrine regulation of cell proliferation and differentiation in confluent Caco-2 cells. Pulse-chase experiments using the two clones endowed with the lowest and highest levels of SI activity, followed by immunoprecipitation of labelled SI with epitope-specific antibodies and SDS/PAGE analysis, suggested that both transcriptional and post-translational mechanisms play a role in the regulation of SI expression in intestinal cells.
Deformable grating optical modulator (1992)

A new type of light modulator, the deformable grating modulator, based on electrically controlling the amplitude of a micromachined phase grating is described. Mechanical motion of one quarter of a wavelength is sufficient for switching in this device. The small mechanical motion allows the use of structures with high mechanical resonance frequencies. We have developed a deformable grating modulator with a bandwidth of 1.8 MHz and a switching voltage of 3.2 V and have demonstrated modulation with 16 dB of contrast. Smaller devices with bandwidths of as much as 6.1 MHz and predicted switching voltages of less than 10 V were also fabricated.
Idiotype vaccination against murine B cell lymphoma. Inhibition of tumor immunity by free idiotype protein. (1987)

A murine B cell lymphoma (38C13) was used as a model to study the induction of idiotype (Id)-specific tumor immunity. Immunization of syngeneic mice with Id protein derived from the tumor resulted in the production of anti-Id antibodies by the host and in the induction of a state of resistance to tumor growth. Tumor immunity could be established only if the Id protein was conjugated to a strongly immunogenic carrier protein such as keyhole limpet hemocyanin or thyroglobulin, and if the conjugate was administered at least 1 week prior to tumor challenge. Free Id protein, such as that present in tumor bearing animals, was found to inhibit tumor immunity in a dose-dependent manner. Although tumor immunity could be induced in animals with pre-existent serum Id protein, the expression of the immune state was inhibited by the presence of the soluble protein.
Clinical Impact of Bortezomib in Frontline Regimens for Patients with Multiple Myeloma (2007)

Standard frontline therapy for multiple myeloma comprises cytoreductive therapy with or without consolidative high-dose therapy plus stem cell transplantation (HDT-SCT). Despite therapeutic advances, the disease remains incurable; most patients relapse following frontline treatment and die within 5 years of diagnosis. New options are required to enhance and prolong response, and improve survival, particularly for elderly patients and those with renal dysfunction. Preclinical studies have demonstrated the ability of bortezomib to enhance the activity of commonly used myeloma agents, an observation validated through clinical studies in both the relapsed and frontline settings. This review focuses on the growing body of clinical evidence showing the effectiveness of bortezomib and bortezomib-based combinations in newly diagnosed patients, characterized by high overall response rates and consistently high rates of complete response. A number of studies incorporating bortezomib as part of induction therapy have demonstrated no adverse impact of bortezomib on stem cell harvest and engraftment in patients proceeding to transplantation. The higher rates of complete response typically associated with bortezomib treatment may potentially improve clinical outcomes in this setting. Final results from ongoing phase III studies of bortezomib-based combinations versus standard regimens will help define the optimal use of bortezomib as a standard component of frontline therapy for multiple myeloma. Disclosure of potential conflicts of interest is found at the end of this article.
Intermodulation distortion in current-commutating CMOS mixers (2000)

The nonlinearity behavior of CMOS current-switching mixers is investigated. By treating the mixer as a periodically-time-varying weakly nonlinear circuit, we study the distortion-causing mechanisms and we predict the mixer distortion performance. Normalized graphs are provided from which the designer can readily estimate the mixer nonlinearity for particular process and design parameters. A simple CMOS transistor model appropriate for our calculations, which also takes into account deviation from the square law is adopted. The significance of a physical transistor model for reliable distortion simulation is demonstrated. The prediction of our analysis is compared with simulation results and with experimental data.
Conjugate Addition Reactions Combined with Free-Radical Cross-Linking for the Design of Materials for Tissue Engineering (2001)

PEG-diacrylamide was synthesized and utilized to make materials for tissue engineering. Acrylamide groups readily react with thiol groups, and peptides containing a single thiol group were coupled to the PEG-diacrylamide in aqueous solution at room temperature in about 2 h. If only a portion of the acrylamide groups were targeted for reaction with peptide, sufficient amounts of PEG-diacrylamide remained to be polymerized by free-radical mechanisms via photoinitiation. The photopolymerization step can be performed in contact with cells, providing a means to produce bioactive scaffolds for tissue engineering. The photopolymerization conditions and precursor composition greatly affect the stiffness of the materials, which subsequently affected cell spreading. The kinetics and extent of cell spreading on the bioactive materials were measured and compared to cell spreading on tissue culture polystyrene. Although the PEG materials resist protein adsorption, the experiments suggest that the cells can secrete extracellular matrix that can adhere to the gels.