gebhart/patrepeval huggingface dataset:
Identification and cloning of an 85‐kDa protein homologous to RING3 that is upregulated in proliferating endothelial cells (2001)

A central event in angiogenesis is proliferation of blood vessels, which plays a major role in the progression of a number of inflammatory and neoplastic diseases. It is responsible for the switch of endothelial cells from an antiangiogenic to an angiogenic phenotype. To identify novel activated/proliferating-related proteins in human endothelial cells, a subtractive immunization approach was used to elicit a host antibody response against human dermal microvascular endothelial cells (HDMECs) stimulated with a potent angiogenic cytokine such as VPF/VEGF165. In this study, a new mAb, LY9, which is highly specific to VPF/VEGF165-activated HDMECs, was isolated. Stimulation of HDMECs by VPF/VEGF165 or basic fibroblast growth factor (bFGF) resulted in a dose-dependent and time-dependent increase in the binding of LY9. On Western-blot analysis, LY9 identified an 85-kDa protein (p85) in the lysates of several endothelial cells derived from microvascular or large vessel sources, the expression of which is dramatically increased by VPF/VEGF165. The mAb also identified p85 in primary cell cultures of human foreskin keratinocytes but failed to recognize human fibroblasts (MRC5) and a number of different human tumor cell lines, including MG63 osteosarcoma and MCF7 breast carcinoma cells. Immunological screening of a human keratinocyte lambdagt11 cDNA expression library with LY9 identified a partial cDNA clone of 750 bp. DNA sequencing of this clone and predicted amino acids showed more than 93% homology to RING3 kinase, a member of a newly described family of bromodomain-containing proteins that transactivates in the nucleus the promoters of a number of the E2F family of transcription factors. This molecule may represent a new signaling target activated by VPF/VEGF165 and bFGF that allows endothelial cells to enter the proliferative phase of the angiogenic process.
Secretory Phospholipase A2, Group IIA Is a Novel Serum Amyloid A Target Gene (2009)

Atherosclerosis is a multifactorial vascular disease characterized by formation of inflammatory lesions. Elevated circulating acute phase proteins indicate disease risk. Serum amyloid A (SAA) is one such marker but its function remains unclear. To determine the role of SAA on aortic smooth muscle cell gene expression, a preliminary screen of a number of genes was performed and a strong up-regulation of expression of secretory phospholipase A(2), group IIA (sPLA(2)) was identified. The SAA-induced increase in sPLA(2) was validated by real time PCR, Western blot analysis, and enzyme activity assays. Demonstrating that SAA increased expression of sPLA(2) heteronuclear RNA and that inhibiting transcription eliminated the effect of SAA on sPLA(2) mRNA suggested that the increase was transcriptional. Transient transfections and electrophoretic mobility shift assays identified CAAT enhancer-binding protein (C/EBP) and nuclear factor kappaB (NFkappaB) as key regulatory sites mediating the induction of sPLA(2). Moreover, SAA activated the inhibitor of NF-kappaB kinase (IKK) in cultured smooth muscle cells. Previous reports showed that interleukin (IL)-1beta up-regulates Pla2g2a gene transcription via C/EBPbeta and NFkappaB. Interestingly, SAA activated smooth muscle cell IL-1beta mRNA expression, however, blocking IL-1 receptors had no effect on SAA-mediated activation of sPLA(2) expression. Thus, the observed changes in sPLA(2) expression were not secondary to SAA-induced IL-1 receptor activation. The association of SAA with high density lipoprotein abrogated the SAA-induced increase in sPLA(2) expression. These data suggest that during atherogenesis, SAA can amplify the involvement of smooth muscle cells in vascular inflammation and that this can lead to deposition of sPLA(2) and subsequent local changes in lipid homeostasis.
LONG-TERM RESULTS OF NEPHRON SPARING SURGERY FOR LOCALIZED RENAL CELL CARCINOMA: 10-YEAR FOLLOWUP (2000)

Partial nephrectomy is effective for localized renal cell carcinoma, providing long-term tumor control with preservation of renal function.
Inhibition of Insulin Receptor Activation by Insulin-like Growth Factor Binding Proteins (1997)

The insulin-like growth factors (IGFs) are transported by a family of high-affinity binding proteins (IGFBPs) that protect IGFs from degradation, limit their binding to IGF receptors, and modulate IGF actions. The six classical IGFBPs have been believed to have no affinity for insulin. We now demonstrate that IGFBP-7/mac25, a newly identified member of the IGFBP superfamily that binds IGFs specifically with low affinity is a high-affinity insulin binding protein. IGFBP-7 blocks insulin binding to the insulin receptor and thereby inhibiting the earliest steps in insulin action, such as autophosphorylation of the insulin receptor beta subunit and phosphorylation of IRS-1, indicating that IGFBP-7 is a functional insulin-binding protein. The affinity of other IGFBPs for insulin can be enhanced by modifications that disrupt disulfide bonds or remove the conserved COOH terminus. Like IGFBP-7, an NH2-terminal fragment of IGFBP-3 (IGFBP-3((1-87))), also binds insulin with high affinity and blocks insulin action. IGFBPs with enhanced affinity for insulin might contribute to the insulin resistance of pregnancy, type II diabetes mellitus, and other pathological conditions.
Chromatographic Isolation of Methionine-containing Peptides for Gel-free Proteome Analysis (2002)

A novel gel-free proteomic technology was used to identify more than 800 proteins from 50 million Escherichia coli K12 cells in a single analysis. A peptide mixture is first obtained from a total unfractionated cell lysate, and only the methionine-containing peptides are isolated and identified by mass spectrometry and database searching. The sorting procedure is based on the concept of diagonal chromatography but adapted for highly complex mixtures. Statistical analysis predicts that we have identified more than 40% of the expressed proteome, including soluble and membrane-bound proteins. Next to highly abundant proteins, we also detected low copy number components such as the E. coli lactose operon repressor, illustrating the high dynamic range. The method is about 100 times more sensitive than two-dimensional gel-based methods and is fully automated. The strongest point, however, is the flexibility in the peptide sorting chemistry, which may target the technique toward quantitative proteomics of virtually every class of peptides containing modifiable amino acids, such as phosphopeptides, amino-terminal peptides, etc., adding a new dimension to future proteome research.
Design of an Emission Ratiometric Biosensor from MerR Family Proteins:  A Sensitive and Selective Sensor for Hg2+ (2007)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTDesign of an Emission Ratiometric Biosensor from MerR Family Proteins: A Sensitive and Selective Sensor for Hg2+Seraphine V. Wegner, Ayse Okesli, Peng Chen, and Chuan HeView Author Information Department of Chemistry, The University of Chicago, 5735 South Ellis Avenue, Chicago, Illinois 60637 Cite this: J. Am. Chem. Soc. 2007, 129, 12, 3474–3475Publication Date (Web):March 3, 2007Publication History Received21 November 2006Revised15 February 2007Published online3 March 2007Published inissue 1 March 2007https://pubs.acs.org/doi/10.1021/ja068342dhttps://doi.org/10.1021/ja068342drapid-communicationACS PublicationsCopyright © 2007 American Chemical SocietyRequest reuse permissionsArticle Views2831Altmetric-Citations255LEARN 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 optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Fluorescence,Genetics,Mercury,Oligomers,Sensors Get e-Alerts
A Convenient Synthesis of 1-Alkyl-1-phenylhydrazines fromN-Aminophthalimide (2003)

Abstract N-Alkylaminophthalimides were synthesized by condensation of N-aminophthalimide with aldehydes, and subsequent reduction of the intermediate with pyridine-borane in acetic acid. N-Phenylation and removal of the phthalimide group gave 1-alkyl-1-phenylhydrazines in high yield.
Automation of the CHARMM General Force Field (CGenFF) II: Assignment of Bonded Parameters and Partial Atomic Charges (2012)

Molecular mechanics force fields are widely used in computer-aided drug design for the study of drug candidates interacting with biological systems. In these simulations, the biological part is typically represented by a specialized biomolecular force field, while the drug is represented by a matching general (organic) force field. In order to apply these general force fields to an arbitrary drug-like molecule, functionality for assignment of atom types, parameters, and partial atomic charges is required. In the present article, algorithms for the assignment of parameters and charges for the CHARMM General Force Field (CGenFF) are presented. These algorithms rely on the existing parameters and charges that were determined as part of the parametrization of the force field. Bonded parameters are assigned based on the similarity between the atom types that define said parameters, while charges are determined using an extended bond-charge increment scheme. Charge increments were optimized to reproduce the charges on model compounds that were part of the parametrization of the force field. A "penalty score" is returned for every bonded parameter and charge, allowing the user to quickly and conveniently assess the quality of the force field representation of different parts of the compound of interest. Case studies are presented to clarify the functioning of the algorithms and the significance of their output data.
Peptide vaccine candidate mimics the heterogeneity of natural SARS-CoV-2 immunity in convalescent humans and induces broad T cell responses in mice models (2020)

Abstract We developed a global peptide vaccine against SARS-CoV-2 that addresses the dual challenges of heterogeneity in the immune responses of different individuals and potential heterogeneity of the infecting virus. PolyPEPI-SCoV-2 is a polypeptide vaccine containing nine 30-mer peptides derived from all four major structural proteins of the SARS-CoV-2. Vaccine peptides were selected based on their frequency as HLA class I and class II personal epitopes (PEPIs) restricted to multiple autologous HLA alleles of individuals in an in silico cohort of 433 subjects of different ethnicities. PolyPEPI-SCoV-2 vaccine administered with Montanide ISA 51VG adjuvant generated robust, Th1-biased CD8 + and CD4 + T cell responses against all four structural proteins of the virus, as well as binding antibodies upon subcutaneous injection into BALB/c and CD34 + transgenic mice. In addition, PolyPEPI-SCoV-2-specific, polyfunctional CD8 + and CD4 + T cells were detected ex vivo in each of the 17 asymptomatic/mild COVID-19 convalescents’ blood investigated, 1–5 months after symptom onset. The PolyPEPI-SCoV-2-specific T cell repertoire used for recovery from COVID-19 was extremely diverse: donors had an average of seven different peptide-specific T cells, against the SARS-CoV-2 proteins; 87% of donors had multiple targets against at least three SARS-CoV-2 proteins and 53% against all four. In addition, PEPIs determined based on the complete HLA class I genotype of the convalescent donors were validated, with 84% accuracy, to predict PEPI-specific CD8 + T cell responses measured for the individuals. Extrapolation of the above findings to a US bone marrow donor cohort of 16,000 HLA-genotyped individuals with 16 different ethnicities (n=1,000 each ethnic group) suggest that PolyPEPI-SCoV-2 vaccination in a general population will likely elicit broad, multi-antigenic CD8 + and CD4 + T cell responses in 98% of individuals, independent of ethnicity, including Black, Asian, and Minority Ethnic (BAME) cohorts.
Assessing Receptor Affinity for Inverse Agonists: Schild and Cheng-Prusoff Methods Revisited (2006)

Classical methods for the estimation of antagonist affinity constants were developed under the assumption of one unique state for the receptor. The finding of receptor constitutive activity, which implies that at least two (one active and the other inactive) receptor states coexist at equilibrium, extended the concept of antagonism by distinguishing between neutral antagonists and inverse agonists. To account for the complexity introduced in the concept of antagonism, classical Schild and Cheng-Prusoff methods have been revisited within the two-state model of agonism. The resulting equations match the classical expressions for neutral antagonists but not for inverse agonists. It is suggested a revision of current routine procedures for antagonist affinity estimation.
The phase compensation scheme for multiple planar antenna on the SOTM (2009)

The antenna of the satellite communication on the move (SOTM) system generally is paraboloid antenna. It is difficult to miniaturize the SOTM system because of the height of the antenna. In some applications it is substituted by the planar phased array antenna. Aiming at the application on vehicle platform the low profile multiple planar antenna system is presented to reduce the antenna height more. The method of two-class phase compensation is provided to resolve the problems of the aperture effect and the aperture transit-time. It can expand working band width of the antenna system. Meanwhile genetic algorithm is applied in adjusting the phase weight of sub-array to optimize the sidelobe level of the antenna pattern. Experiments show that the scheme of the multiple planar antenna has similar performance to the planar antenna while fulfilling the height demand of vehicle platform. It is hopeful in applications.
The role of complement in ocular pathology (2008)

Functionally active complement system and complement regulatory proteins are present in the normal human and rodent eye. Complement activation and its regulation by ocular complement regulatory proteins contribute to the pathology of various ocular diseases including keratitis, uveitis and age-related macular degeneration. Furthermore, a strong relationship between age-related macular degeneration and polymorphism in the genes of certain complement components/complement regulatory proteins is now well established. Recombinant forms of the naturally occurring complement regulatory proteins have been exploited in the animal models for treatment of these ocular diseases. It is hoped that in the future recombinant complement regulatory proteins will be used as novel therapeutic agents in the clinic for the treatment of keratitis, uveitis, and age-related macular degeneration.
Approximately uniform random sampling in sensor networks (2004)

Recent work in sensor databases has focused extensively on distributed query problems, notably distributed computation of aggregates. Existing methods for computing aggregates broadcast queries to all sensors and use in-network aggregation of responses to minimize messaging costs. In this work, we focus on uniform random sampling across nodes, which can serve both as an alternative building block for aggregation and as an integral component of many other useful randomized algorithms. Prior to our work, the best existing proposals for uniform random sampling of sensors involve contacting all nodes in the network. We propose a practical method which is only approximately uniform, but contacts a number of sensors proportional to the diameter of the network instead of its size. The approximation achieved is tunably close to exact uniform sampling, and only relies on well-known existing primitives, namely geographic routing, distributed computation of Voronoi regions and von Neumann's rejection method. Ultimately our sampling algorithm has the same worst-case asymptotic cost as routing a point-to-point message, and thus it is asymptotically optimal among request/reply-based sampling methods. We provide experimental results demonstrating the effectiveness of our algorithm on both synthetic and real sensor topologies.
Superantigens: Mechanism of T-Cell Stimulation and Role in Immune Responses (1991)

Superantigens combine with MHC class-II molecules to form the ligands that stimulate T cells via the V beta element of the T-cell receptor. Two groups of superantigens have been described so far: first, endogenous murine products that include the Mls determinants, and second, bacterial products such as the Staphylococcal enterotoxins. Here, we review studies that address the interactions between the foreign superantigens and MHC class-II molecules, the mechanism of T-cell stimulation, and the role that tolerance to self-superantigens plays in shaping the T-cell repertoire. We speculate on the possible evolutionary significance of superantigens.
Complete amino acid sequence of NADPH-cytochrome P-450 reductase from porcine hepatic microsomes (1986)

The complete amino acid sequence of porcine hepatic microsomal NADPH-cytochrome P-450 reductase has been determined by microsequence analysis on several sets of proteolytic fragments. Sequence studies were performed initially on a 20-kilodalton (kDa) fragment and then on 80-kDa fragment. The amino-terminal end of the mature protein was blocked with an acetyl group, followed by 676 amino acid residues. It has been revealed that the COOH-terminal 20-kDa fragment has been derived from original enzyme by cleavage at the Asn-Gly (residues 502-503) linkage by an unknown mechanism. An NADPH-protected cysteine residue is located at residue 565, near a region exhibiting high sequence homology with ferredoxin-NADP+ reductase. The FMN and FAD binding regions are possibly located in the amino-terminal region and the middle part of the protein molecule, respectively, as suggested by Porter and Kasper [Porter, T. D., & Kasper, C. B. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 973-977]. When this sequence is compared with that of rat enzyme, 60 amino acid residues are substituted, probably due to species differences. However, total sequence homology between these enzymes is 90%. Hydropathy plot analysis reveals that two regions from residues 27-43 and from residues 523-544 exhibit a high degree of hydrophobicity, suggesting membrane binding or interaction with cytochrome P-450.
Distortion free LINC amplifier with chireix- outphasing combiner using phase-only predistortion (2004)

A LlNC amplifier with perfectly balanced branches and a Chireir-outphasing combiner is studied and the sources of its nonlinearity are identified. A phase-only predistortion function is derived in explicit form and used to linearize this amplifier. The predistortion function preserves constant envelope operation of the amplifiers. The impact of the predistortion function on the combiner efficiency is also investigated. It is found, through simulation with a CDMA signal that the predistortion function linearizes perfectly the amplifier. It is also shown, that with perfect linearity, the efficiency of Chireix-outphasing amplifier reduces to that of the LINC amplifier with a resistive combiner.
High-Frequency Lamb Wave Device Composed of LiNbO3Thin Film (2009)

It has been considered that it is difficult to realize a high-frequency device of 3 GHz or more, for instance, for a fourth generation mobile phone system in Japan, using a conventional surface acoustic wave (SAW) substrate. In this study, we attempted to fabricate a high-frequency resonator using Lamb waves, which has a high velocity and consists of a thin LiNbO3 film deposited by chemical vapor deposition (CVD). As a result, a 1-port Lamb wave resonator composed of an electrode/thin epitaxial LiNbO3 film/air-gap/base substrate was fabricated. The measured resonator has a high resonant frequency of 4.5 GHz, which corresponds to a very high velocity of 14,000 m/s, a large impedance ratio of 52 dB, and a relatively wide bandwidth of 7.2%.
METHYLNALTREXONE CHANGES GUT MOTILITY AND TRANSIT TIME IN CHRONIC METHADONE-MAINTAINED SUBJECTS* (1999)

S404 Constipation is the most common side effect of opioids and can be a severe problem in patients with chronic opioid pain therapy. [1] Methylnaltrexone (MNTX), a peripheral opioid receptor antagonist, offers the therapeutic potential of decreasing the side effects of opioids in the gut while preserving analgesia. [2] As a paradigm for cancer patients receiving chronic opioid therapy, we evaluated the effects of intravenous MNTX on subjects receiving chronic methadone therapy. METHODS: All protocols were approved by the IRB. In Study 1, the lactulose hydrogen breath test [3] was used to assess gastrointestinal transit time in 9 males and 10 females (mean age +/- SD 37.2 +/- 8.0 yr) who were chronically receiving methadone. Results of oral-cecal transit times were compared with results obtained from a previous study in healthy volunteers. Wilcoxon matched pairs signed rank test was used for statistical comparison. In Study 2, 4 subjects (2 males and 2 females) with opioid-induced constipation from chronic methadone therapy received placebo on day 1 and iv MNTX (0.05-0.45 mg/kg) twice daily for the rest of the week in a single-blind protocol. Oral-cecal transit time was recorded as well as laxation response based on the frequency and consistency of stools during the study period. Pharmacokinetic data were collected and analyzed. RESULTS: Constipation was experienced by 58% of our subjects. Mean oral-cecal transit time without MNTX was 159 +/- 49.2 min, significantly longer than the transit time in our previous study of volunteers (105 +/- 32 min, P < 0.01). These results suggest that chronic opioid use does not induce tolerance in the gut. In the second study, 2 subjects who received MNTX 0.45 mg/kg (a dose previously used in volunteers) showed immediate positive laxation with infusion. Of these, 1 subject had severe abdominal cramping but showed no other signs of systematic withdrawal such as lacrimation, diaphoresis, mydriasis, or hallucinations. In the remaining 2 subjects, MNTX was reduced to 0.05-0.15 mg/kg. They also had immediate laxation with mild abdominal cramping during and after medication. Stool frequency increased from 2-3 times/week before the study to 1.785 times/day during the treatment period. Gut transit times were reduced from 150 min (baseline) 5o 60 min for each subject by the end of the study. CONCLUSION: Tolerance to opioids does not appear to extend to gastrointestinal motility and transit. Low-dose MNTX transit time in chronic methadone subjects. Low-dose MNTX effectively reversed opioid-induced constipation and delay in gut transit time in chronic methadone subjects. We expect that cancer patients receiving opioids chronically also will have increased sensitivity to MNTX. Low-dose MNTX may have clinical utility in managing opioid-induced constipation. Supported in part by the IARS; Clinical Practice Enhancement & Anesthesia Research Foundation; grant M01 RR00055 from the U.S. Public Health Service General Clinical Research Center