gebhart/patrepeval huggingface dataset:
Transport of heparan sulfate into the nuclei of hepatocytes. (1986)

Monolayer cultures of a rat hepatocyte cell line shown previously to accumulate a nuclear pool of free heparan sulfate chains that are enriched in sulfated glucuronic acid (GlcA) residues (Fedarko, N.S., and Conrad, H.E., (1986) J. Cell Biol. 587-599) were incubated with 35SO4(2-), and the rate of appearance of heparan [35S]sulfate in the nuclei was measured. Heparan [35S]sulfate began to accumulate in the nuclei 2 h after the administration of 35SO4(2-) to the cells and reached a steady state level after 20 h. Heparan [35S]sulfate was lost from the nuclei of prelabeled cells with a t1/2 of 8 h. Chloroquine did not inhibit the transport of heparan sulfate into the nucleus, but increased the t1/2 for the exit of heparan sulfate from the nucleus to 20 h and led to a doubling of the steady state level of nuclear heparan sulfate. Heparan [35S]sulfate which was obtained from the medium or from the cell matrix of a labeled culture and which contained only low levels of GlcA-2-SO4 residues was incubated with cultures of unlabeled cells, and the uptake of the exogenous heparan [35S]sulfate was studied. At 37 degrees C the cells took up proteoheparan [35S]sulfate and transported about 10% of the internalized heparan [35S]sulfate into the nucleus, where it appeared as free chains. The heparan [35S]sulfate isolated from the nucleus was enriched in GlcA-2-SO4 residues, whereas the heparan [35S]sulfate remaining in the rest of the intracellular pool showed a corresponding depletion in GlcA-2-SO4 residues. At 16 degrees C, where endocytosed materials do not enter the lysosomes, the cells also transported exogenous proteoheparan [35S]sulfate to the nucleus with similar processing. Thus, the metabolism of exogenous heparan sulfate by hepatocytes follows the same pathway observed in continuously labeled cells and does not involve lysosomal processing of the internalized heparan sulfate.
Modified Vaccinia Virus Ankara Induces Toll-Like Receptor-Independent Type I Interferon Responses (2007)

Modified vaccinia virus Ankara (MVA) is a highly attenuated vaccinia virus strain undergoing clinical evaluation as a replication-deficient vaccine vector against various infections and tumor diseases. To analyze the basis of its high immunogenicity, we investigated the mechanism of how MVA induces type I interferon (IFN) responses. MVA stimulation of bone marrow-derived dendritic cells (DC) showed that plasmacytoid DC were main alpha IFN (IFN-alpha) producers that were triggered independently of productive infection, viral replication, or intermediate and late viral gene expression. Increased IFN-alpha levels were induced upon treatment with mildly UV-irradiated MVA, suggesting that a virus-encoded immune modulator(s) interfered with the host cytokine response. Mice devoid of Toll-like receptor 9 (TLR9), the receptor for double-stranded DNA, mounted normal IFN-alpha responses upon MVA treatment. Furthermore, mice devoid of the adaptors of TLR signaling MyD88 and TRIF and mice deficient in protein kinase R (PKR) showed IFN-alpha responses that were only slightly reduced compared to those of wild-type mice. MVA-induced IFN-alpha responses were critically dependent on autocrine/paracrine triggering of the IFN-alpha/beta receptor and were independent of IFN-beta, thus involving "one-half" of a positive-feedback loop. In conclusion, MVA-mediated type I IFN secretion was primarily triggered by non-TLR molecules, was independent of virus propagation, and critically involved IFN feedback stimulation. These data provide the basis to further improve MVA as a vaccine vector.
Derivatives of the muscarinic agent N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide (1988)

A series of tertiary and quaternary analogues (acyclic imides, sulfonimides, N-acetyl sulfonamides, and trifluoroacetamides) of the selective partial muscarinic agonist N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide (BM 5,35) was synthesized. The compounds were found to be muscarinic agonists, partial agonists, or antagonists in the isolated guinea pig ileum. Replacement of the acetyl group or the N-methyl group of 35 and its analogues by a methanesulfonyl group abolished efficacy and decreased affinity at ileal muscarinic receptors. Trifluoroacetamide analogues of 35 also had lower affinity and efficacy than 35. Substitution of an acetyl group for the N-methyl group in compounds related to 35 decreased efficacy, but had no appreciable effect on affinity. Most of the tertiary amines showed central antimuscarinic activity as they antagonized oxotremorine-induced tremors in mice.
Three-dimensional microscopy with phase-shifting digital holography (1998)

We applied phase-shifting digital holography to microscopy by deriving the complex amplitude of light scattered from microscopic three-dimensional objects through a microscope objective by video camera recording, phase-shifting analysis, and computer reconstruction. This method requires no mechanical movement and provides a flexible display and quantitative evaluation of the reconstructed images. A theory of image formation and experimental verification with specimens are described.
임상연구 : 자궁경부 국소적 진행암에서 선행 화학요법으로서 Cisplatin , Ifosfamide , Paclitaxel ( CIP ) 의 phase II 연구 (2000)

목적 : 본 연구는 국소적으로 진행한 자궁경부 편평 세포암환자를 대상으로 Cisplatin,Ifosfamide, Paclitaxel(CIP)을 이용한 선행화학요법의 효과 및 독성을 연구하기 위한 목적으로 설정되었다
방법 : 1997년 2월부터 1999년 2월까지 자궁 경부 편평 세포암으로 확진된 40명(28 Ib2-IIa, 5 IIb, 4 IIIa, 2 IIIb, 1 IVa)의 환자를 대상으로 하였으며, 첫째날 paclitaxel 175mg/㎡를, 둘째날 cisplatin 50mg/㎡와 ifosfamide 5g/㎡, mesna 5mg/㎡를, 그리고 세째날 mesna 3mg/㎡을 투여하여 각 3주간 격으로 3회의 치료를 시행한 후 광범위 자궁적출술 및 임파선 절제술을 시행, 그 반응성을 조사하였다.결과 : 모든 40명의 환자의 임상적 반응율을 평가하였으며 또한 35명의 환자에서 수술을 시행하여 병리학적 반응율을 평가하여 으로 7예의 환자에서 완전 반응을 보였고 8예에서 적절한 부분 반응을 보였으며, 15예에서 미흡한 부분반응을, 5예에서 무반응양상을 보였고 평균 19개월간(15-31개월) 추적 조사한 결과 35예는 재발 없이 생존하였고, 4예에서 재발하였으며 나머지 1예는 사망하였다. 또한 독성에 관한 결과가 조사되었으나 그로 인한 심각한 합병증은 발생하지 않았다.
결론 : 국소적으로 진행된 자궁경부 편평 세포암에 있어서의 CIP regimen을 사용한 본 연구에서 병리학적 완전 반응 및 적정 부분 반응을 보인 경우는 37.5%로 나타났으며, 비교적 수용 가능한 범위 내에서의 독성 반응을 나타냈다. 앞으로는 본 약물을 이용한 선행화학 요법으로 질병의 진행여부 및 생존율 등 반응에 관한 좀 더 많은 예의 평가연구가 시행되어져야 할 것으로 생각된다.
The use of gold nanoparticles to enhance radiotherapy in mice (2004)

Mice bearing subcutaneous EMT-6 mammary carcinomas received a single intravenous injection of 1.9 nm diameter gold particles (up to 2.7 g Au/kg body weight), which elevated concentrations of gold to 7 mg Au/g in tumours. Tumour-to-normal-tissue gold concentration ratios remained approximately 8:1 during several minutes of 250 kVp x-ray therapy. One-year survival was 86% versus 20% with x-rays alone and 0% with gold alone. The increase in tumours safely ablated was dependent on the amount of gold injected. The gold nanoparticles were apparently non-toxic to mice and were largely cleared from the body through the kidneys. This novel use of small gold nanoparticles permitted achievement of the high metal content in tumours necessary for significant high-Z radioenhancement.
The topology of drug–target interaction networks: implicit dependence on drug properties and target families (2009)

The availability of interaction data between small molecule drugs and protein targets has increased substantially in recent years. Using seven different databases, we were able to assemble a total of 4767 unique interactions between 802 drugs and 480 targets, which means that on average every drug is currently acknowledged to interact with 6 targets. The application of network theory to the analysis of these data reveals an unexpectedly complex picture of drug-target interactions. The results confirm that the topology of drug-target networks depends implicitly on data completeness, drug properties, and target families. The implications for drug discovery are discussed.
Biochemical analysis of the epithelin receptor (1993)

Epithelin 1 and 2 are cysteine-rich proteins that act as growth modulators of epithelial cells. In this report, we have characterized the epithelins receptors of MDA-MB-468 human breast carcinoma cells using both binding and cross-linking techniques. Equilibrium binding studies of iodinated epithelin 1 indicated that two classes of binding sites are expressed at the surface of breast carcinoma cells. The high affinity sites had a dissociation constant of approximately 2 x 10(-10) M, with approximately 290 receptors/cell. The low affinity sites had a dissociation constant of approximately 10(-8) M, with approximately 32,000 receptors/cell. Binding of iodinated epithelin 1 was specifically inhibited by unlabeled epithelin 1, 2, or 3, but not by other growth factors tested. We also performed competition binding studies of 125I-epithelin 1 to cell surface receptors in the presence of unlabeled epithelin 1, 2, or 3. Binding results analyzed by the method of Scatchard suggested that all three epithelins interact with a same receptor. A 140-145-kDa epithelin 1-binding protein complex was identified by chemical cross-linking of 125I-epithelin 1 to breast cancer cells. Formation of such a complex was prevented by coincubation of 125I-epithelin 1 with an excess of unlabeled epithelin 1, 2, or 3.
Strains of Actinomyces naeslundii and Actinomyces viscosus Exhibit Structurally Variant Fimbrial Subunit Proteins and Bind to Different Peptide Motifs in Salivary Proteins (1999)

Oral strains of Actinomyces spp. express type 1 fimbriae, which are composed of major FimP subunits, and bind preferentially to salivary acidic proline-rich proteins (APRPs) or to statherin. We have mapped genetic differences in the fimP subunit genes and the peptide recognition motifs within the host proteins associated with these differential binding specificities. The fimP genes were amplified by PCR from Actinomyces viscosus ATCC 19246, with preferential binding to statherin, and from Actinomyces naeslundii LY7, P-1-K, and B-1-K, with preferential binding to APRPs. The fimP gene from the statherin-binding strain 19246 is novel and has about 80% nucleotide and amino acid sequence identity to the highly conserved fimP genes of the APRP-binding strains (about 98 to 99% sequence identity). The novel FimP protein contains an amino-terminal signal peptide, randomly distributed single-amino-acid substitutions, and structurally different segments and ends with a cell wall-anchoring and a membrane-spanning region. When agarose beads with CNBr-linked host determinant-specific decapeptides were used, A. viscosus 19246 bound to the Thr42Phe43 terminus of statherin and A. naeslundii LY7 bound to the Pro149Gln150 termini of APRPs. Furthermore, while the APRP-binding A. naeslundii strains originate from the human mouth, A. viscosus strains isolated from the oral cavity of rat and hamster hosts showed preferential binding to statherin and contained the novel fimP gene. Thus, A. viscosus and A. naeslundii display structurally variant fimP genes whose protein products are likely to interact with different peptide motifs and to determine animal host tropism.
The Roles of Osteoprotegerin and Osteoprotegerin Ligand in the Paracrine Regulation of Bone Resorption (2000)

Although multiple hormones and cytokines regulate various aspects of osteoclast formation, the final two effectors are osteoprotegerin ligand (OPG-L)/osteoclast differentiation factor (ODF), a recently cloned member of the tumor necrosis factor superfamily, and macrophage colony-stimulating factor. OPG-L/ODF is produced by osteoblast lineage cells and exerts its biological effects through binding to its receptor, osteoclast differentiation and activation receptor (ODAR)/receptor activator of NF-kappa B (RANK), on osteoclast lineage cells, in either a soluble or a membrane-bound form, the latter of which requires cell-to-cell contact. Binding results in rapid differentiation of osteoclast precursors in bone marrow to mature osteoclasts and, at higher concentrations, in increased functional activity and reduced apoptosis of mature osteoclasts. The biological activity of OPG-L/ODF is neutralized by binding to osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF), a member of the TNF-receptor superfamily that also is secreted by osteoblast lineage cells. The biological importance of this system is underscored by the induction in mice of severe osteoporosis by targeted ablation of OPG/OCIF and by the induction of osteopetrosis by targeted ablation of OPG-L/ODF or overexpression of OPG/OCIF. Thus, osteoclast formation may be determined principally by the relative ratio of OPG-L/ODF to OPG/OCIF in the bone marrow microenvironment, and alterations in this ratio may be a major cause of bone loss in many metabolic disorders, including estrogen deficiency and glucocorticoid excess. That changes in but two downstream cytokines mediate the effects of large numbers of upstream hormones and cytokines suggests a regulatory mechanism for osteoclastogenesis of great efficiency and elegance.
Mobility Enhancement in Modulation‐Doped Si ‐ Si1 − x   Ge x Superlattice Grown by Molecular Beam Epitaxy (1986)

We report the first observation of enhanced electron mobility in strained layer superlattices grown on Si substrates by molecular beam epitaxy. A alloy layer between substrate and superlattice provides for a strain distribution on both the Si and the layers in the superlattice. The superlattice layers are modulation doped by Sb. At an average doping level of , a mobility enhancement at room temperature of more than a factor 5 is obtained compared to equivalently doped bulk Si. Maximum mobility is achieved with modulation doping of just the lower gap . Temperature dependent Hall measurements show a clearly reduced impurity scattering of the electrons, indicating the existence of a two‐dimensional electron gas.
Sequence Composition Effects on the Energetics of Triple Helix Formation by Oligonucleotides Containing a Designed Mimic of Protonated Cytosine (1995)

A nonnatural nucleoside, 1- (2-deoxy-β-ribofuranosyl)-3-methyl-5-amilHn-op-y razol0[4,3-d]pyrimidin-7-one (P), mimics protonated cytosine and specifically binds GC base pairs within a pyrimidine.purine.pyrimidine triple helix. Quantitative footprint titration experiments at neutral pH (22 °C, 100 mM NaCl, 10 mM bis-tris, 250 μM spermine) reveal dramatic sequence composition effects on the energetics of triple helix formation by oligonucleotides containing P or 5-methylcytosine (^mC). Purine tracts of sequence composition 5'-d(AAAAAGAGAGAGAGA)-3' are bound by oligonucleotide 5'-d (TTTTT^mCT^mCT^mCT^mCT^mCT)-3' 4 orders of magnitude more strongly than by 5'-d (TTTTTPTPTPTPTPT)-3' (K_T ≈ 3 x l0^9 M^(-1) and KT = 1 x l0^5 M^(-1), respectively). Conversely, purine tracts of sequence composition 5'-d(AAAAGAAAAGGGGGGA)-3' are bound by oligonucleotide 5'-d(TTTT^mCTTTT)-3' 5 orders of magnitude less strongly than by 5'-d(TTTT^mCTTTTPPPPPPT)-3' (K_T &lt; 5 x l0^4 M^(-1) and K_T ≈ 4 x l0^9 M^(-1), respectively). The complementary nature of P and ^mC expands the repertoire of G-rich sequences which may be targeted by triple helix formation.
Using Cooccurrence Statistics and the Web to Discover Synonyms in a Technical Language (2004)

Turney (2001) has shown that computing the mutual information of a pair of words by using cooccurrence counts obtained via queries to the AltaVista search engine performs very effectively in a synonym detection task. Since manual synonym detection is a challenging task for terminologists, we investigate whether the AltaVista-based Mutual Information (AVMI) method can be applied to the task of finding pairs of synonyms in the lexicon of a specialized sub-language. In particular, we experiment with synonyms in the field of nautical terminology. Our results indicate that AVMI is very good at spotting synonym couples among pairs of unrelated terms (with precision close to 90% at 62.5% recall) and that it outperforms more standard methods based on contextual cosine similarity. However, AVMI is not able to distinguish between synonyms and other semantically related terms. Thus, AVMI can be used for synonym mining only if it is combined with techniques to filter out other semantic relations. 1.
Superconductivity at 40 K in the Oxygen-Defect Perovskites La 2- x Sr x CuO 4- y (1987)

Structural, magnetic, and electronic properties of compounds in the series La2-xSrx CuO4-y for 0.05 </= x </= 1.1, with deltax = 0.025, were studied. Resistance, susceptibility, Meissner, and shielding measurements have revealed superconductivity among several members of the series. For x = 0.15, the transition temperature T(c), measured at the midpoint of the resistive transition, is a maximum at 39.3 K with a width of 2 K. At other compositions the transition is broader and occurs at a lower temperature. Annealing the x = 0.15 sample in oxygen at 500 degrees C increases T(c) to 40.3 K, while annealing at the same temperature under vacuum suppresses the superconductivity. These changes in oxygen content and T(c) are reversible.
Human immunodeficiency virus type 1 gp120 envelope glycoprotein regions important for association with the gp41 transmembrane glycoprotein (1991)

Insertion of four amino acids into various locations within the amino-terminal halves of the human immunodeficiency virus type 1 gp120 or gp41 envelope glycoprotein disrupts the noncovalent association of these two envelope subunits (M. Kowalski, J. Potz, L. Basiripour, T. Dorfman, W. C. Goh, E. Terwilliger, A. Dayton, C. Rosen, W. A. Haseltine, and J. Sodroski, Science 237:1351-1355, 1987). To localize the determinants on the gp120 envelope glycoprotein important for subunit association, amino acids conserved among primate immunodeficiency viruses were changed. Substitution mutations affecting either of two highly conserved regions located at the amino (residues 36 to 45) and carboxyl (residues 491 to 501) ends of the mature gp120 molecule resulted in nearly complete dissociation of the envelope glycoprotein subunits. Partial dissociation phenotypes were observed for some changes affecting residues in the third and fourth conserved gp120 regions. These results suggest that hydrophobic regions at both ends of the gp120 glycoprotein contribute to noncovalent association with the gp41 transmembrane glycoprotein.
Bioactive β‐bend structures for the antagonist hα CGRP8–37 at the CGRP1 receptor of the rat pulmonary artery (2000)

The aim of this study was to determine beta-bend structures and the role of the N- and C-terminus in the antagonist halpha CGRP(8 - 37) at the rat pulmonary artery CGRP receptor mediating halpha CGRP relaxation. Halpha CGRP(8 - 37) Pro(16) (10(-6) M), with a bend-biasing residue (proline) at position 16, did not antagonize halpha CGRP responses, while a structure-conserving amino acid (alanine(16)) at the same position retained antagonist activity (apparent pK(B) 6.6+/-0.1; 10(-6) M). Halpha CGRP(8 - 37) Pro(19) (10(-6) M), with proline at position 19 was an antagonist (apparent pK(B) 6.9+/-0.1). Incorporation of a beta-bend forcing residue, BTD (beta-turn dipeptide), at positions 19 and 20 in halpha CGRP(8 - 37) (10(-6) M) antagonized halpha CGRP responses (apparent pK(B) 7.2+/-0.2); and BTD at positions 19,20 and 33,34 within halpha CGRP(8 - 37) was a competitive antagonist (pA(2) 7.2; Schild plot slope 1.0+/-0.1). Halpha CGRP(8 - 37) analogues, substituted at the N-terminus by either glycine(8) or des-NH(2) valine(8) or proline(8) were all antagonists (apparent pK(B) 6.9+/-0.1; (10(-6) M), 7.0+/-0.1 (10(-6) M), and pA(2) 7.0 (slope 1.0+/-0.2), respectively); while replacements by proline(8) together with glutamic acid(10,14) in halpha CGRP(8 - 37) (10(-6) M) or alanine amide(37) at the C-terminus of halpha CGRP(8 - 37) (10(-5) M) were both inactive compounds. In conclusion, possible bioactive structures of halpha CGRP(8 - 37) include two beta-bends (at 18 - 21 and 32 - 35), which were mimicked by BTD incorporation. Within halpha CGRP(8 - 37), the N-terminus is not essential for antagonism while the C-terminus may interact directly with CGRP(1) receptors in the rat pulmonary artery.
Preliminary Study on the Cleavage of Fusion Protein GST-CMIV with Palladium(II) Complex (2000)

A novel method for post-treatment of gene-engineered proteins is reported. A coden of Cys-His unit is introduced into the N-terminal of cecropin CMIV by using PCR. The gene is expressed in E. coli fused with GST. After purification, the fusion protein is cleaved by [Pd(en)(H2O)2]2+ at the His-Arg bond and the cecropin CMIV with antibacterial activity is obtained. The preliminary results held some promise of success for application of the palladium(II) complex as cleavage agent for the production of peptide drugs from gene-engineering fusion proteins.
Candidabiofilms on implanted biomaterials: a clinically significant problem (2006)

In recent years there has been an increasing appreciation that microbial biofilms are ubiquitous, which has resulted in a number of studies on infectious diseases from a biofilm perspective. Biofilms are defined as structured microbial communities that are attached to a surface and encased in a matrix of exopolymeric material. A wide range of biomaterials used in clinical practice have been shown to support colonization and biofilm formation by Candida spp., and the increase in Candida infections in the last decades has almost paralleled the increase and widespread use of a broad range of medical implant devices, mainly in populations with impaired host defenses. Formation of Candida biofilms has important clinical repercussions because of their increased resistance to antifungal therapy and the ability of cells within biofilms to withstand host immune defenses. Further recognition and understanding of the role of Candida biofilms in human infection should help in the clinical management of these recalcitrant infections.
Percolation of Code to Enhance Parallel Dispatching and Execution (1972)

This note investigates the increase in parallel execution rate as a function of the size of an instruction dispatch stack with lookahead hardware. Under the constraint that instructions are not dispatched until all preceding conditional branches are resolved, stack sizes as small as 2 or 4 achieve most of the parallelism that a hypothetically infinite stack would.
Discovery of a Nanomolar Inhibitor of the Human Murine Double Minute 2 (MDM2)−p53 Interaction through an Integrated, Virtual Database Screening Strategy (2006)

An integrated, virtual database screening strategy has led to 7-[anilino(phenyl)methyl]-2-methyl-8-quinolinol (4, NSC 66811) as a novel inhibitor of the murine double minute 2 (MDM2)-p53 interaction. This quinolinol binds to MDM2 with a Ki of 120 nM and activates p53 in cancer cells with a mechanism of action consistent with targeting the MDM2-p53 interaction. It mimics three p53 residues critical in the binding to MDM2 and represents a promising new class of non-peptide inhibitors of the MDM2-p53 interaction.
A simplified assay for O6-methylguanine-DNA methyltransferase activity and its application to human neoplastic and non-neoplastic tissues (1984)

A rapid assay of O6-MeG-DNA methyltransferase activity is described. Following incubation of cell extracts with O6-[3H]MeG-containing DNA, remaining radioactive DNA was hydrolyzed in trichloroacetic acid and separated from methylated radioactive protein by filtration or centrifugation. Transfer of radioactive methyl from DNA to protein was proportional to the amount of protein added, and was not linear with time. More than 90% of the radioactivity precipitated after acid hydrolyses was in S-methyl cysteine residues. The method was used to measure O6-MeG-DNA methyltransferase activity in extracts of 24 neoplastic tissues from human organs. Although five tumor tissues had 28-84% lower activity of O6-MeG-DNA methyltransferase than the corresponding normal tissue from the same patient, higher or similar levels of activity were found more frequently. Thus, a lack of O6-MeG-DNA methyltransferase activity in human tumours appears not to be a frequent event. The DNA repair enzyme uracil-DNA glycosylase was also measured in the same extracts. Most frequently the level of uracil-DNA glycosylase activity was essentially similar in tumors and normal tissues but significantly higher or lower levels were also observed.