gebhart/patrepeval huggingface dataset:
Role of Immune Checkpoint Proteins in Idiopathic Pulmonary Fibrosis (2017)

Abstract Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease, with unknown etiopathogenesis and suboptimal therapeutic options. Due to the lack of clinical efficacy of standard immuno-suppressants in IPF, the role of the immune response in this disease remains elusive. Nevertheless, previous reports have shown that increased T cell numbers and phenotype is predictive of prognosis in IPF, suggesting that these cells might have a role in this disease. Transcriptomic analysis of CD3 + T cells isolated from IPF lungs removed prior to lung transplant (i.e. explant lung) revealed a loss of CD28 expression and both elevated checkpoint and lymphocyte activation pathways. Flow cytometric analysis of a mixture of immune and non-immune cells isolated from explanted IPF lungs showed elevated PD-1 and CTLA4 protein expression on CD4 - lymphocytes and PD-L1 expression on EpCAM + and CD45 - EpCAM - cells. Lung remodeling and loss of BAL surfactant protein C were observed in NOD SCID IL-2R γ -/- (NSG) mice that received an intravenous injection of a mixture of IPF cells, including purified IPF T cells. Finally, in humanized NSG mice, anti-CTLA4, but not anti-PD1, mAb treatment induced an expansion of CD3 + T cells and accelerated lung fibrosis. Together, these results demonstrate that IPF T cells are profibrotic but the immune checkpoint protein, CTLA-4, appears to limit this effect in IPF.
Developments in suicide genes for preclinical and clinical applications. (2000)

The graduation of gene therapy from unfulfilled dreams to conventional therapy for genetic and acquired disorders will require a mastery of multiple disparate components including gene delivery vectors, regulated tissue-specific gene expression, control of immunity and manipulation of cell viability. Improvements in suicide genes have opened up a whole new treatment modality for treating hyperproliferative disorders and for designing animal models for disease. Along with herpes simplex virus-1 thymidine kinase, a host of additional suicide genes have been developed. A critical comparison of these will follow along with progress in utilizing these reagents for therapeutic benefits.
Symbiotic Expression of Cosmid-Borne Bradyrhizobium japonicum Hydrogenase Genes (1987)

The expression of cosmid-borne Bradyrhizobium japonicum hydrogenase genes in alfalfa, clover, and soybean nodules harboring Rhizobium transconjugants was studied. Cosmid pHU52 conferred hydrogen uptake (Hup) activity in both free-living bacteria and in nodules on the different plant hosts, although in nodules the instability of the cosmid resulted in low levels of Hup activity. In contrast, cosmid pHU1, which does not confer Hup activity on free-living bacteria, gave a Hup phenotype in nodules on alfalfa and soybean. Nodules formed by B. japonicum USDA 123Spc(pHU1) recycled about 90% of nitrogenase-mediated hydrogen evolution. Both subunits of hydrogenase (30- and 60-kilodalton polypeptides) were detected in enzyme-linked immunosorbent assays of bacteroid preparations from nodules harboring B. japonicum strains with pHU1 or pHU52. Neither pHU53 nor pLAFR1 conferred detectable Hup activity in either nodules or free-living bacteria. Based on the physical maps of pHU1 and pHU52, it is suggested that a 5.5-kilobase EcoRI fragment unique to pHU52 contains a gene or part of a gene required for Hup activity in free-living bacteria but not in nodules. This conclusion is supported by the observation that two Tn5 insertions in the chromosome of B. japonicum USDA 122DES obtained by marker exchange with Tn5-mutagenized pHU1 abolished Hup activity in free-living bacteria but not in nodules.
Association of Eotaxin gene family with asthma and serum total IgE (2003)

The Eotaxin gene family (Eotaxin1, Eotaxin2 and Eotaxin3) recruits and activates CCR3-bearing cells such as eosinophils, mast cells and Th2 lymphocytes that play a major role in allergic disorders. To date, the effect of polymorphisms of Eotaxin genes on asthma phenotypes has not been thoroughly examined. In our research, we sequenced whole regions of the Eotaxin gene family to identify polymorphisms, which may be involved in the development of asthma and total serum IgE. We have identified 37 SNPs in the Exotaxin gene family (Exotaxin1, 2 and 3), and 17 common polymorphic sites were selected for genotyping in our asthma cohort (n=721). Statistical analysis revealed that the EOT2+1265A>G G* allele showed significantly lower frequency in asthmatics than in normal healthy controls (0.14 versus 0.23, P=0.002), and that distribution of the EOT2+1265A>G G* allele-containing genotypes was also much lower in asthmatics (26.3 versus 40.8%, P=0.003). In addition, a non-synonymous SNP in Eotaxin1, EOT1+123Ala>Thr showed significant association with total serum IgE levels (P=0.002-0.02). The effect of EOT1+123Ala>Thr on total serum IgE appeared in a gene-dose-dependent manner. Our findings suggest that the development of asthma may be associated with EOT2+1265A>G polymorphisms, and the susceptibility to high IgE production may be attributed to the EOT1+123Ala>Thr polymorphism. Eotaxin variation/haplotype information identified in this study might provide valuable insights into strategies for the control of asthma.
Characterization of radioligand binding to a transmembrane receptor reconstituted into Lipobeads (2004)

Lipobeads are hydrogel beads surrounded by a lipid bilayer membrane and have been developed to act as a cell analogue. The FLAG-tagged M(2) muscarinic receptor was incorporated onto the surface of the Lipobead by incubating pre-Lipobeads with proteoliposomes containing the receptor. Receptors reconstituted onto the surface of the Lipobeads were functional in that they bound the antagonists quinuclidinylbenzilate and scopolamine with characteristic muscarinic affinities. This demonstrates the feasibility of using Lipobeads to study the binding properties of the M(2) muscarinic receptor and offers a promising approach to the study of transmembrane protein biology in general.
Improved efficacy for ezetimibe and rosuvastatin by attenuating the induction of PCSK9 (2011)

Reducing circulating LDL-cholesterol (LDL-c) reduces the risk of cardiovascular disease in people with hypercholesterolemia. Current approaches to reduce circulating LDL-c include statins, which inhibit cholesterol synthesis, and ezetimibe, which blocks cholesterol absorption. Both elevate serum PCSK9 protein levels in patients, which could attenuate their efficacy by reducing the amount of cholesterol cleared from circulation. To determine whether PCSK9 inhibition could enhance LDL-c lowering of both statins and ezetimibe, we utilized small interfering RNAs (siRNAs) to knock down Pcsk9, together with ezetimibe, rosuvastatin, and an ezetimibe/rosuvastatin combination in a mouse model with a human-like lipid profile. We found that ezetimibe, rosuvastatin, and ezetimibe/rosuvastatin combined lower serum cholesterol but induce the expression of Pcsk9 as well as the Srebp-2 hepatic cholesterol biosynthesis pathway. Pcsk9 knockdown in combination with either treatment led to greater reductions in serum non-HDL with a near-uniform reduction of all LDL-c subfractions. In addition to reducing serum cholesterol, the combined rosuvastatin/ezetimibe/Pcsk9 siRNA treatment exhibited a significant reduction in serum APOB protein and triglyceride levels. Taken together, these data provide evidence that PCSK9 inhibitors, in combination with current therapies, have the potential to achieve greater reductions in both serum cholesterol and triglycerides.
Design of slotted waveguide antenna with slot depth variation (2013)

본 논문에서는 슬롯의 깊이를 변화시켜 X-밴드에서 동작하는 1.4m길이의 도파관 슬롯배열 안테나를 설계하였다. 54개의 슬롯배열이 모델링되어 CST로 시뮬레이션 되었으며 부엽레벨은 주어진 주파수 범위에서 효과적으로 억압되었다. 안테나의 측정 결과 이득은 21.8dB, 최대 부엽레벨은 -31dB, 반전력빔폭은 <TEX>$2.0^{\circ}$</TEX>의 결과를 얻을 수 있었다. We design a slotted waveguide antenna for X-band which a 1.4m length with slot depth variation. A 54 slot array is modeled and simulated by CST, and the side lobe level is suppressed effectively in a certain range of frequency. The experimental results of the antenna show that its gain, maximum sidelobe level and half power beam-width are 21.8dB, -31dB and 2.0deg, respectively.
A FORTRAN Coloring Book (1978)

right way to a FORTRAN book, the author of this one tells us now that we've almost to its last page, by a series of skimming passes. Each time through you pick up a bit more of the nitty-gritty detail. When you pick up an IBM manual, for instance, first flip through it looking for the jokes. There aren't any, so go back and flip through again, getting familiar with the overall idea. Then flip through from back to front, side to side, and top to bottom. If there's a centerfold, you're in the wrong publication! Each time through, you'll be looking for specific details connected with whatever you are doing at the time on the computer. After a while, the whole works will have seeped through your skin by osmosis. This introduction to FORTRAN works like that, squared. Or unsquared. Anyway, it's unlike any technical manual or textbook you've ever seen. You may you're chuckling knowingly at some felicitous irreverence the author has craftily inserted, or gravely pondering a remark by one of his cartoon animals, or groaning over an especially outrageous pun. You may even think you're just coloring the giraffe yellow. But you're really learning FORTRAN--how to use it, how to keep it from using you--on the sly. High school kids can deal with it. The book will also appeal to, like, college sophomores, since it revels in a brand of collegiate humor that is just not going to go away, that is going to last--alas--through generations of computers. And sophomores, nowadays, are finding that FORTRAN is more often a prerequisite or academic requirement than is, oh, French, just to mention another popular modern language.The book teaches its readers all they need to know to get a start at programming real computers about such things as algorithms, the arithmetic if, array storage, artichokes, assignment statements, branches, bugs (including those in programs), call statements, complex constants, conditional branches, control statements, dimension statements, do loops, dummy arguments, errors, exponential notation, floating point numbers, floormats, the Gauss-Seidel method, go-to statements, hierarchy, integer field specifications, Kaufman, line printers, logical assignment statements, mixed modes, nested implied do loops, parentheses, prunes, read statements, recursion relations, relational operators, specification statements, Spiro Whatsisname, storage, subprograms, type statements, unary and ornery operators, write statements, X-field specifications, and you-can't-get-there-from-here statements.That's not all, folks, and not in that order. Like any good book that's not a dictionary, this one is ordered in a functional rather than alphabetical way, but some of these topics think they deserve top billing, so...Roger Kaufman first tried out his coloring book in a course he taught to MIT freshmen. They liked it just fine, and said so in their formal course evaluation. They probably learned FORTRAN better--more accurately, more memorably--than they would have from some stuffy text.Dr. Kaufman the book. I mean, he wrote it, the actual words you see, with a pen. He also drew the pictures, diagrams, flow charts, and things.
Influence of micronutrients on rheological characteristics and bread-making quality of flour (2008)

Studies were carried out to see the influence of different iron and calcium salts along with some vitamins on the rheological characteristics and bread-making quality of wheat flour. Fortification with iron (30-90 ppm) from different sources showed a marginal increase in water absorption (2%). Calcium ranging between 800 and 1,600 ppm did not show any influence on the mixing properties of the dough. Except for ethylenediamine tetraacetic acid and calcium lactate, all other salts did not have any influence on the alveograph characteristics. The gelatinization temperature slightly increased by about 2-3 degrees C and the cold paste viscosity increased from 468 to 524 BU. Addition of micronutrient premix containing ferrous sulphate, calcium carbonate and vitamins such as thiamine (thiamine hydrochloride), riboflavin, niacin (nicotinic acid) and folic acid at different levels showed a marginal effect on the rheological parameters. There was no significant influence of micronutrient premix on the objective and subjective evaluation of the breads, except for the crumb colour. Fortification with the vitamin-mineral premix did not affect the theological parameters and bread-making quality of flour, even after storage.
Magnetic forces in high-T(sub c) superconducting bearings (1990)

In September 1987 research at Cornell levitated a small rotor on superconducting bearing at 10,000 rpm. In April 1989 a speed of 120,000 rpm was achieved in a passive bearing with no active control. The bearing material used was YBa2Cu3O7. There is no evidence that the rotation speed has any significant effect on the lift force. Magnetic force measurements between a permanent rare-earth magnet and high T(sub c) superconducting material versus vertical and lateral displacements were made. A large hysteresis loop results for large displacements, while minor loops result for small displacements. These minor loops seem to give a slope proportional to the magnetic stiffness, and are probably indicative of flux pinning forces. Experiments of rotary speed versus time show a linear decay in a vacuum. Measurements of magnetic drag forces of a magnetic dipole over a high-T(sub c) superconducting disc of YBCO show that the drag force reaches a constant value, independent of the speed. Dampling of lateral vibrations of levitated rotors were measured which indicates that transverse flux motion in the superconductor will create dissipation. As a result of these force measurements, an optimum shape for the superconductor bearing pads which gives good lateral and axial stability was designed. Recent force measurements on melt-quench processed superconductors indicate a substantial increase in levitation force and magnetic stiffness over free sintered materials. As a result, application of high-T(sub c) superconducting bearings are beginning to show great promise at this time.
Terpestacin Inhibits Tumor Angiogenesis by Targeting UQCRB of Mitochondrial Complex III and Suppressing Hypoxia-induced Reactive Oxygen Species Production and Cellular Oxygen Sensing (2010)

Cellular oxygen sensing is required for hypoxia-inducible factor-1alpha stabilization, which is important for tumor cell survival, proliferation, and angiogenesis. Here we find that terpestacin, a small molecule previously identified in a screen of microbial extracts, binds to the 13.4-kDa subunit (UQCRB) of mitochondrial Complex III, resulting in inhibition of hypoxia-induced reactive oxygen species generation. Consequently, such inhibition blocks hypoxia-inducible factor activation and tumor angiogenesis in vivo, without inhibiting mitochondrial respiration. Overexpression of UQCRB or its suppression using RNA interference demonstrates that it plays a crucial role in the oxygen sensing mechanism that regulates responses to hypoxia. These findings provide a novel molecular basis of terpestacin targeting UQCRB of Complex III in selective suppression of tumor progression.
Identification of Residues Essential for Human Paraoxonase (PON1) Arylesterase/Organophosphatase Activities (1999)

Human serum paraoxonase (PON1) is a calcium-dependent organophosphatase. To identify residues essential for PON1 activity, we adopted complementary approaches based on chemical modification and site-directed mutagenesis. To detect 45Ca2+ binding to native and chemically modified PON1, we performed nondenaturating gel electrophoresis. The environment of calcium-binding sites was probed using the Ca2+ analogue, terbium. Tb3+ binds to calcium-binding sites as shown by displacement of 45Ca2+ by Tb3+. Binding of Tb3+ is accompanied by a complete loss of enzyme activity. PON1 chemical modification with the Trp-selective reagent, N-bromosuccinimide, and the Asp/Glu-selective, dicyclohexylcarbodiimide, established that Trp and Asp/Glu residues are components of the PON1 active center and calcium-binding sites. Additional evidence for the presence of a Trp residue in the PON1 calcium-binding sites was a characteristic fluorescence emission at 545 nm from the PON1-Tb3+ complex and abolishment of that fluorescence upon modification by N-bromosuccinimide. The importance of aromatic/hydrophobic character of the residue 280 was demonstrated by site-directed mutagenesis: the W280F mutant was fully active while the W280A and W280L mutants had markedly reduced activity. Twelve amino acids among conserved His and Asp/Glu residues were found essential for PON1 arylesterase and organophosphatase activities: H114, H133, H154, H242, H284, D53, D168, D182, D268, D278, E52, and E194. Finally, the cysteines constituting the PON1 disulfide bond (C41 and C352) were essential, but the glycan chains linked to Asn 252 and 323 were not essential for PON1 secretion and activity.
A General, Regioselective Synthesis of 2-Alkenylanilines (1995)

Reduction of selected 2,1-benzothiazines with sodium amalgam leads to the formation of 2-alkenylanilines in high yield. The benzothiazines are readily available from the reaction of N-phenyl-S-(p-tolyl)sulfonimidoyl chloride with alkynes in the presence of aluminum chloride. The sulfonimidoyl chloride is derived from aniline, and the process described herein thus constitutes a high-yielding, regioselective functionalization of aniline.
Comparative Studies on the Carbohydrate-containing membrane components of normal and virus-transformed mouse fibroblasts. II. Separation of glycoproteins and glycopeptides by Sephadex chromatography (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTComparative Studies on the Carbohydrate-containing membrane components of normal and virus-transformed mouse fibroblasts. II. Separation of glycoproteins and glycopeptides by Sephadex chromatographyElias Meezan, Henry C. Wu, Paul H. Black, and Phillips W. RobbinsCite this: Biochemistry 1969, 8, 6, 2518–2524Publication Date (Print):June 1, 1969Publication History Published online1 May 2002Published inissue 1 June 1969https://doi.org/10.1021/bi00834a039RIGHTS & PERMISSIONSArticle Views346Altmetric-Citations202LEARN 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 InReddit PDF (616 KB) Get e-Alerts Get e-Alerts
A Novel Src Homology 3 Domain-containing Adaptor Protein, HIP-55, That Interacts with Hematopoietic Progenitor Kinase 1 (1999)

Hematopoietic progenitor kinase 1 (HPK1) is a member of the mitogen-activated protein kinase kinase kinase kinase (MAP4K) family and an upstream activator of the c-Jun N-terminal kinase (JNK) signaling cascade. HPK1 interacts, through its proline-rich domains, with growth factor receptor-bound 2 (Grb2), CT10-regulated kinase (Crk), and Crk-like (CrkL) adaptor proteins. We identified a novel HPK1-interacting protein of 55 kDa (HIP-55), similar to the mouse SH3P7 protein, containing an N-terminal actin-binding domain and a C-terminal Src homology 3 domain. We found that HPK1 bound to HIP-55 both in vitro and in vivo. When co-transfected, HIP-55 increased HPK1's kinase activity as well as JNK1's kinase activity. A dominant-negative HPK1 mutant blocked activation of JNK1 by HIP-55 showing that HIP-55 activates the JNK1 signaling pathway via HPK1. Our results identify a novel protein, HIP-55, that binds to HPK1 and regulates the JNK1 signaling cascade.
Emerging application of quantum dots for drug delivery and therapy (2008)

Quantum dots have proven themselves as powerful fluorescent probes, especially for long-term, multiplexed, and quantitative imaging and detection. Newly engineered quantum dots with integrated targeting, imaging and therapeutic functionalities have become excellent material to study drug delivery in cells and small animals. This fluorescent 'prototype' will provide important information in the rational design of biocompatible drug carriers and will serve as a superior alternative to magnetic and radioactive imaging contrast agents in preclinical drug screening, validation and delivery research. This Editorial article is not intended to offer a comprehensive review on drug delivery, but to highlight the breakthroughs in the emerging applications of quantum dots in this field and to provide our perspective on future research.
Inability of a Fusion Protein of IL-2 and Diphtheria Toxin (Denileukin Diftitox, DAB389IL-2, ONTAK) to Eliminate Regulatory T Lymphocytes in Patients With Melanoma (2005)

Elimination of regulatory T lymphocytes may provide a way to break self-tolerance and unleash the anti-tumor properties of circulating lymphocytes. The use of fusion proteins, which link cytotoxic molecules to receptor targets, provides one approach to this problem. This study examined the ability of a fusion protein of interleukin-2 (IL-2) and diphtheria toxin (Denileukin Diftitox, DAB389IL-2, ONTAK) to eliminate regulatory T lymphocytes based on their expression of high-affinity IL-2 receptors. Thirteen patients (12 with metastatic melanoma, 1 with metastatic renal cell carcinoma) were treated at one of the two Food and Drug Administration-approved doses of Denileukin Diftitox (seven patients at 9 microg/kg, six patients at 18 microg/kg). None of the patients experienced an objective clinical response. Foxp3 expression did not decrease significantly overall, although it did decrease minimally among patients receiving 18 microg/kg (-2.01+/-0.618 copies of Foxp3/10(3) copies of beta-actin; P=0.031). Denileukin Diftitox did not decrease the suppressive ability of CD4CD25 cells as quantified by an in vitro co-culture suppression assay. Furthermore, the increased numbers of lymphocytes in patients resulting from treatment with IL-2 were not susceptible to Denileukin Diftitox. Administration of Denileukin Diftitox does not appear to eliminate regulatory T lymphocytes or cause regression of metastatic melanoma.
Modulation and Chirp Characterization of a 100-GHz EO Polymer Mach-Zehnder Modulator (2011)

We experimentally characterize a 100-GHz polymer Mach-Zehnder modulator including its frequency chirp response and broadband data modulation. BER performance is achieved at 80 Gbit/s for DPSK and &gt;90 Gbit/s for OOK. Tunable chirp operation is demonstrated while eye diagrams at 100 Gbit/s and 110-GHz S21 measurements further demonstrate the &gt; 100-GHz response.
Phase II Study of the Farnesyl Transferase Inhibitor R115777 in Patients With Advanced Non–Small-Cell Lung Cancer (2003)

Single-agent R115777 was well tolerated in patients with advanced NSCLC, but demonstrated minimal clinical activity. Inhibition of farnesylation in vivo was consistently documented. On the basis of promising results of farnesyl transferase inhibitor combinations with standard chemotherapy agents, future studies of this agent in NSCLC should be in combination with systemic chemotherapy.