gebhart/patrepeval huggingface dataset:
Extinction of Insulin-Like Growth Factor-I Mitogenic Signaling by Antiestrogen-Stimulated Fas-Associated Protein Tyrosine Phosphatase-1 in Human Breast Cancer Cells (1998)

Steroidal (ICI 182, 780) and nonsteroidal hydroxytamoxifen (OH-Tam) antiestrogens inhibit growth factor-mitogenic activity in MCF 7 estrogen receptor-positive human breast cancer cells. Cell inhibition is correlated with an increase in membrane protein tyrosine phosphatase (PTP) activity, and the addition of orthovanadate prevents OH-Tam inhibition. After RT-PCR cloning of PTPs expressed in MCF 7 cells with primers to their catalytic domains, we have shown, by differential screening, that the expression of two enzymes, leukocyte common antigen-related PTP (LAR) and Fas-associated PTP-1 (FAP-1), was modulated by antiestrogens. By comparative RT-PCR, in situ hybridization, and Northern blot, LAR and FAP-1 mRNAs accumulation was found to be dose- and time-dependently increased by antiestrogens. To further demonstrate that PTPs were key mediators of antiestrogen-inhibitory action on the growth factor pathway, a panel of stable FAP-1 transfectants expressing low to high levels of antisense mRNAs was established. In these clones, the level of antisense RNA expression was correlated with a reduction in basal levels and a complete inhibition of antiestrogen-stimulated values of PTP activity. When FAP-1 expression was abolished, OH-Tam was no longer able to block insulin-like growth factor I mitogenic activity even though it remained strongly antiestrogenic. However, ICI 182,780 was still inhibitory, indicating that its effect was not exclusively mediated by PTP. Our data first demonstrate that a specifically regulated phosphatase (FAP-1) is implicated in the triggering of negative proliferation signals in breast cancer cells.
Luteinizing Hormone-Releasing Hormone-Binding Sites in the Rat Thymus: Characteristics and Biological Function (1989)

The present study was designed to explore the effects of LHRH and its agonists on immune system function. As a first step, to identify a putative site of action, the very potent and stable LHRH agonist (LHRH-A), [D-Ser(TBU6)] des-Gly10-LHRH ethylamide (buserelin), was used as an iodinated ligand to characterize LHRH receptors in a membrane preparation of rat thymus, a key organ of the immune system. The effects of LHRH and LHRH-A were then investigated on the proliferative capacity of rat thymocytes exposed in vitro to a mitogen and on ornithine decarboxylase specific activity. In addition, to determine whether LHRH-A treatment in vivo might directly influence thymic function, we treated hypophysectomized (hypox) rats with a moderately high dose of LHRH-A for a period of 2 weeks, and thymocyte mitogenic capacity, thymus weight, and the histological and functional appearance of the thymus were then assessed. Specific binding of LHRH-A to rat thymic membrane preparations is a saturable process, depending on both time and temperature of incubation, but differs markedly from binding to the rat pituitary or ovarian LHRH receptor in its low binding affinity. Binding is optimal in the absence of chelating agents (EDTA) or divalent metal ions, and increases linearly with increasing protein concentration. Binding is specific for LHRH, LHRH-A, and antagonists. Both the C-terminal amide and N-terminal regions of the LHRH molecule were required for binding, and amino acid substitutions at position 6 markedly enhanced and at position 8 markedly reduced binding potencies in rat thymic tissue. A number of peptides, proteins, and other agents had no effect on the specific binding of LHRH-A to thymic membrane preparations. The binding affinity (Ka) of the membrane receptor of the rat thymus for the LHRH superagonist buserelin was 8.4 x 10(8) M-1, while a higher binding affinity (Ka = 2.8 x 10(9) M-1) was calculated for the ovarian LHRH-binding site. Preincubation of rat thymocytes with LHRH-A for 20 h induced a significant dose-dependent increase in the proliferative response to the mitogen Concanavalin-A, monitored by [3H]thymidine incorporation. Using native LHRH, it was also possible to elicit stimulatory effects on the same parameter, although much higher concentrations were required than with LHRH-A. Furthermore, simultaneous addition of a LHRH antagonist, abolished the LHRH effect on thymocytes. Ornithine decarboxylase specific activity under lectin stimulation was also significantly increased by LHRH-A in cultures of rat thymocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
Tumour blood flow modification by endothelin-related peptides in the rat HSN fibrosarcoma. (1996)

Modification of tissue blood flow and tissue vascular resistance was examined in the female CBH rat, bearing a HSN fibrosarcoma, following bolus intravenous administration of 1 nM kg-1 endothelin-1 (ET-1) or 1 nM kg-1 sarafotoxin S6c (SX6c), selective agonists for endothelin A (ETA) and B (ETB) receptors respectively. Blood flow was measured 15 min after drug administration by the tissue uptake of 125I-labelled-iodoantipyrine. ET-1 and SX6c produced increases in mean arterial blood pressure (MABP) of 52 mmHg and 42 mmHg respectively. Blood flow to the tumour was unaffected by ET-1 treatment, whereas blood flow to normal tissues was reduced, the exception being the heart and the brain in which flow was increased. In contrast, tumour blood flow following SX6c was significantly increased, whereas blood flow in normal tissues was either unaltered or reduced. Vascular resistance was increased in all tissues and the tumour by ET-1 demonstrating that the tumour vasculature was constricting via ETA receptor activation. SX6c however, did not modify tumour vascular resistance, whereas it increased vascular resistance in all normal tissues, suggesting that the tumour lacks a functional population of ETB receptors. This discrepancy may provide a means for selectively modifying tumour blood flow.
ChemInform Abstract: MESOIONIC METHINE DYES OF BIQUATERNARY SALTS OF DIHETEROARYL METHANES ‐ DERIVATIVES OF 1,3,4‐OXA(THIA)DIAZOLES AND 1,2,4‐TRIAZOLES (1984)

Abstract Das Bis‐Q‐phenylhydrazid) (I) der Malonsäure reagiert mit Säureanhydriden (II) in der angegebenen Weise zu den diquartären Salzen (IIIa) und (IIIb), (Va)‐(Vc) und (VIa) und (VIb).
The Effects of Particle Size and Molecular Targeting on the Intratumoral and Subcellular Distribution of Polymeric Nanoparticles (2010)

The current study describes the impact of particle size and/or molecular targeting (epidermal growth factor, EGF) on the in vivo transport of block copolymer micelles (BCMs) in athymic mice bearing human breast cancer xenografts that express differential levels of EGF receptors (EGFR). BCMs with diameters of 25 nm (BCM-25) and 60 nm (BCM-60) were labeled with indium-111 ((111)In) or a fluorescent probe to provide a quantitative and qualitative means of evaluating their whole body, intratumoral, and subcellular distributions. BCM-25 was found to clear rapidly from the plasma compared to BCM-60, leading to an almost 2-fold decrease in their total tumor accumulation. However, the tumoral clearance of BCM-25 was delayed through EGF functionalization, enabling the targeted BCM-25 (T-BCM-25) to achieve a comparable level of total tumor deposition as the nontargeted BCM-60 (NT-BCM-60). Confocal fluorescence microscopy combined with MATLAB analyses revealed that NT-BCM-25 diffuses further away from the blood vessels (D(mean) = 42 +/- 9 microm) following extravasation, compared to NT-BCM-60 which mainly remains in the perivascular regions (D(mean) = 23 +/- 4 microm). The introduction of molecular targeting imposes the "binding site barrier" effect, which retards the tumor penetration of T-BCM-25 (D(mean) = 29 +/- 7 microm, p < 0.05). The intrinsic nuclear translocation property of EGF/EGFR leads to a significant increase in the nuclear uptake of T-BCM-25 in vitro and in vivo via active transport. Overall, these results highlight the need to consider multiple design parameters in the development of nanosystems for delivery of anticancer agents.
24/7 place recognition by view synthesis (2015)

We address the problem of large-scale visual place recognition for situations where the scene undergoes a major change in appearance, for example, due to illumination (day/night), change of seasons, aging, or structural modifications over time such as buildings built or destroyed. Such situations represent a major challenge for current large-scale place recognition methods. This work has the following three principal contributions. First, we demonstrate that matching across large changes in the scene appearance becomes much easier when both the query image and the database image depict the scene from approximately the same viewpoint. Second, based on this observation, we develop a new place recognition approach that combines (i) an efficient synthesis of novel views with (ii) a compact indexable image representation. Third, we introduce a new challenging dataset of 1,125 camera-phone query images of Tokyo that contain major changes in illumination (day, sunset, night) as well as structural changes in the scene. We demonstrate that the proposed approach significantly outperforms other large-scale place recognition techniques on this challenging data.
Urinary 8-hydroxy-2'-deoxyguanosine as a biological marker of in vivo oxidative DNA damage. (1989)

DNA is subject to constant oxidative damage from endogenous oxidants. The oxidized DNA is continuously repaired and the oxidized bases are excreted in the urine. A simple routine analytical procedure is described for urinary 8-hydroxy-2'-deoxyguanosine, an oxidative DNA damage adduct, as an indicator of oxidative damage in humans and rodents. This adduct was purified from human urine and characterized. The described assay employs a series of solid-phase extraction steps that separate 8-hydroxy-2'-deoxyguanosine from other urinary constituents, followed by analysis by gradient reversed-phase HPLC coupled to a dual-electrode high-efficiency electrochemical detection system. Analysis of urine from three species by this method indicates that mice excrete approximately 3.3-fold more 8-hydroxy-2'-deoxyguanosine than humans (582 vs. 178 residues per cell per day), a result that supports the proposal that oxidative damage to DNA increases in proportion to species-specific basal metabolic rates.
A 25-Signal Proteomic Signature and Outcome for Patients With Resected Non–Small-Cell Lung Cancer (2007)

We defined a mass spectrometry signature that was associated with survival among NSCLC patients and appeared to distinguish those with poor prognosis from those with good prognosis.
Temperature-sensitive Mutants of Herpes Simplex Virus Type 2 (1971)

Microbiology Society journals contain high-quality research papers and topical review articles. We are a not-for-profit publisher and we support and invest in the microbiology community, to the benefit of everyone. This supports our principal goal to develop, expand and strengthen the networks available to our members so that they can generate new knowledge about microbes and ensure that it is shared with other communities.
Some Unconventional Organic−Inorganic Hybrid Low-Dimensional Semiconductors and Related Light-Emitting Devices (2011)

Structural, optical, electrical, and optoelectronic properties, as well as prototype light-emitting devices, are being reported for the two-dimensional (quantum well) organic−inorganic hybrid semiconductor systems based on the organic cations CH3(CH2)7CH═CH(CH2)8NH3+ (OL) and on the inorganic networks formed out of MX42− anions, where M = Pb and X = I, Br, and Cl. These new crystalline compounds show extremely intense excitonic bands at chemically controllable positions in the ultraviolet−visible spectral region, with excitonic binding energies of more than 180 meV at room temperature. These novel properties render them as strong potential candidates in optoelectronic applications, comparable to the artificial low-dimensional systems. Prototype light-emitting devices (LED) based on the above-mentioned compounds exhibit naked eye electroluminescence, in some cases, semicontinuous operation, for the first time at room temperature. In addition, these devices operate at relatively low voltages and are readily realized. Because of the enhanced film-forming and degradation-resistant properties of the active materials, the device functionality is being exhibited for weeks. Thus, it is expected that this particular reported synthetic route of hybrid organic−inorganic semiconductors could provide cost-effective materials for novel optoelectronic devices. Moreover, the properties of some composite systems of the type (CH3NH3)n−1(OL)2PbnX3n+1 are being reported briefly.
Translational Efficiency Is Regulated by the Length of the 3′ Untranslated Region (1996)

All polyadenylated mRNAs contain sequence of variable length between the coding region and the poly(A) tail. Little has been done to establish what role the length of the 3' untranslated region (3'UTR) plays in posttranscriptional regulation. Using firefly luciferase (luc) reporter mRNA in transiently transfected Chinese hamster ovary (CHO) cells, we observed that the addition of a poly(A) tail increased expression 97-fold when the length of the 3'UTR was 19 bases but that its stimulatory effect was only 2.3-fold when the length of the 3'UTR was increased to 156 bases. The effect of the luc 3'UTR on poly(A) tail function was orientation independent, suggesting that its length and not its primary sequence was the important factor. Increasing the length of the 3'UTR increased expression from poly(A)- mRNA but had little effect on poly(A)+ mRNA. To examine the effect of length on translational efficiency and mRNA stability, a 20-base sequence was introduced and reiterated downstream of the luc stop codon to generate a nested set of constructs in which the length of the 3'UTR increased from 4 to 104 bases. For poly(A)- reporter mRNA, translational efficiency in CHO cells increased 38-fold as the length of the 3'UTR increased from 4 to 104 bases. Increasing the length of the 3'UTR beyond 104 bases increased expression even further. Increasing the length of the 3'UTR also resulted in a 2.5-fold stabilization of the reporter mRNA. For poly(A)+ mRNA, the translational efficiency and mRNA half-life increased only marginally as the length of the 3'UTR increased from 27 to 161 bases. However, positioning the poly(A) tail only 7 bases downstream of the stop codon resulted in a 39-fold reduction in the rate of translation relative to a construct with a 27-base 3'UTR, which may be a consequence of the poly(A) tail-poly(A)-binding protein complex functioning as a steric block to translocating ribosomes as they approached the termination codon. The optimal length of the 3' noncoding region for maximal poly(A) tail-mediated stimulation of translation is approximately 27 bases. These data suggest that the length of the 3'UTR plays an important role in determining both the translational efficiency and the stability of an mRNA.
Third component of human complement: purification from plasma and physicochemical characterization (1976)

The third component of complement has been purified from fresh human plasma employing an initial fractionation with poly(ethylene glycol) followed by sequential depletion of plasminogen by affinity adsorbents, chromatography on diethylaminoethylcellulose, gel filtration on agarose, and batch adsorption/desorption on hydroxylapatite. Final recoveries of C3 were 33% of the initial protein, as quantitated by radial immunodiffusion, and 31% of the initial hemolytic activity. Apparent homogeneity is indicated by immunological criteria and by polyacrylamide gel electrophoresis. A partial specific volume of 0.736 +/- 0.003 mlgm-1 was determined for C3 by the mechanical oscillator technique. "Low speed" sedimentation equilibrium yielded an apparent weight average molecular weight for the protein of 187 650 +/- 5650. Based upon this molecular weight, a molar extinction coefficient of 1.82 X 10(5) 1. mole-1 cm-1 at 280 nm was calculated from boundary-spreading experiments in the ultracentrifuge and as assumed refractive index increment. Amino acid analyses revealed no unusual or distinctive characteristics. Automated Edman degradation revealed a double N-terminal sequence, Ser-Val,Pro-Glx,Met-Lee,Tyr-Thr,Ser-Glx,Ile-Lys,Gly-Arg,Thr-Met,Pro-Asx, in agreement with the two chain structure observed on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, and revealing both chains are available to degradation. Serine is postulated as the initiating sequence in both chains based upon high recoveries of dinitrophenylserine upon hydrolysis of dinitrophenylated C3, and our inability to identify any other dinitrophenyl or phenylthiohydantoin derivatives in this position. Alanine is the ultimate carboxy-terminal amino acid of at least one of the chains, as indicated by the action of carboxypeptidases on C3 in the presence of sodium dodecyl sulfate.
mGluR2 positive allosteric modulators: a patent review (2009 – present) (2013)

Advances in medicinal chemistry and pharmacology have set the stage in the field of mGlu2 receptor PAMs. Compounds currently advancing in clinical trials will soon establish the therapeutic potential of this allosteric approach.
Entropically driven phase separation of highly branched/linear polyolefin blends (2000)

Small-angle neutron scattering (SANS) was used to examine the melt phase behavior of a heavily branched comb PEE polymer blended separately with two linear PEE copolymers. In this case, PEE refers to poly(ethylene-r-ethylethylene) with 10% ethylene units; therefore, the molecular architecture was the only difference between the two components of the blends. The molecular weights of the two linear random copolymers were 60 and 220 kg/mol, respectively. The comb polymer contained an average of 54 long branches, with a molecular weight of 13.7 kg/mol, attached to a backbone with a molecular weight of 10 kg/mol. Three different volume compositions (25/75, 50/50, and 75/25) were investigated for both types of blends. SANS results indicate that all the blends containing the lower molecular weight linear polymer formed single-phase mixtures, whereas all the blends containing the high molecular weight linear polymer phase-separated. These results are discussed in the context of current theories for polymer blend miscibility. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 2965–2975, 2000
Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy (2005)

Imaging living organisms with molecular selectivity typically requires the introduction of specific labels. Many applications in biology and medicine, however, would significantly benefit from a noninvasive imaging technique that circumvents such exogenous probes. In vivo microscopy based on vibrational spectroscopic contrast offers a unique approach for visualizing tissue architecture with molecular specificity. We have developed a sensitive technique for vibrational imaging of tissues by combining coherent anti-Stokes Raman scattering (CARS) with video-rate microscopy. Backscattering of the intense forward-propagating CARS radiation in tissue gives rise to a strong epi-CARS signal that makes in vivo imaging possible. This substantially large signal allows for real-time monitoring of dynamic processes, such as the diffusion of chemical compounds, in tissues. By tuning into the CH(2) stretching vibrational band, we demonstrate CARS imaging and spectroscopy of lipid-rich tissue structures in the skin of a live mouse, including sebaceous glands, corneocytes, and adipocytes, with unprecedented contrast at subcellular resolution.
Large surface profile measurement with instantaneous phase-shifting interferometry (2003)

Surface profile measurement of smooth surfaces is a vital area in many of today's industries, especially in wafer fabrication. The increased need for high-speed, noncontact online measurement with high accuracy and repeatability is of great interest for practical purposes. In this work, a modification of Michelson interferometers in combination with instantaneous phase-shifting interferometry is proposed for high-speed large flat-surface profiling. Experiments are carried out on a patterned wafer surface. The results obtained using this system are compared with a commercial profiler system to demonstrate the validity of the principle.
Practical guidelines for B-cell receptor repertoire sequencing analysis (2015)

High-throughput sequencing of B-cell immunoglobulin repertoires is increasingly being applied to gain insights into the adaptive immune response in healthy individuals and in those with a wide range of diseases. Recent applications include the study of autoimmunity, infection, allergy, cancer and aging. As sequencing technologies continue to improve, these repertoire sequencing experiments are producing ever larger datasets, with tens- to hundreds-of-millions of sequences. These data require specialized bioinformatics pipelines to be analyzed effectively. Numerous methods and tools have been developed to handle different steps of the analysis, and integrated software suites have recently been made available. However, the field has yet to converge on a standard pipeline for data processing and analysis. Common file formats for data sharing are also lacking. Here we provide a set of practical guidelines for B-cell receptor repertoire sequencing analysis, starting from raw sequencing reads and proceeding through pre-processing, determination of population structure, and analysis of repertoire properties. These include methods for unique molecular identifiers and sequencing error correction, V(D)J assignment and detection of novel alleles, clonal assignment, lineage tree construction, somatic hypermutation modeling, selection analysis, and analysis of stereotyped or convergent responses. The guidelines presented here highlight the major steps involved in the analysis of B-cell repertoire sequencing data, along with recommendations on how to avoid common pitfalls.
A Novel Pyridazinone Derivative Inhibits Hepatitis B Virus Replication by Inducing Genome-Free Capsid Formation (2015)

Here we first identified a novel pyridazinone derivative, compound 3711, as a nonnucleosidic hepatitis B virus (HBV) inhibitor in a cell model system. 3711 decreased extracellular HBV DNA levels by 50% (50% inhibitory concentration [IC50]) at 1.5 ± 0.2 μM and intracellular DNA levels at 1.9 ± 0.1 μM, which demonstrated antiviral activity at levels far below those associated with toxicity. Both the 3TC/ETV dually resistant L180M/M204I mutant and the adefovir (ADV)-resistant A181T/N236T mutant were as susceptible to 3711 as wild-type HBV. 3711 treatment induced the formation of genome-free capsids, a portion of which migrated faster on 1.8% native agarose gel. The induced genome-free capsids sedimented more slowly in isopycnic CsCl gradient centrifugation without significant morphological changes. 3711 treatment decreased levels of HBV DNA contained in both secreted enveloped virion and naked virus particles in supernatant. 3711 could interfere with capsid formation of the core protein (Cp) assembly domain. A Cp V124W mutant, which strengthens capsid interdimer interactions, recapitulated the effect of 3711 on capsid assembly. Pyridazinone derivative 3711, a novel chemical entity and HBV inhibitor, may provide a new opportunity to combat chronic HBV infection.
ChemInform Abstract: CHEMICAL SYNTHESIS OF A HEAT‐STABLE ENTEROTOXIN PRODUCED BY ENTEROTOXIGENIC ESCHERICHIA COLI STRAIN 18D (1984)

Abstract Für das hitzebeständige Enterotoxin aus dem ente rotoxigenen Ecoli‐Stamm 18D sind früher die Strukturen (IVa) bzw. (IVb) vorgeschlagen worden.