gebhart/patrepeval huggingface dataset:
New Insights Into the Pathogenesis of Serous Ovarian Cancer and Its Clinical Impact (2008)

There are only a handful of concepts concerning cancer and carcinogenesis that are currently beyond dispute. One such dogma is the adenoma-carcinoma sequence and that a multistep accumulation of genetic alterations is required for transformation from a benign to a neoplastic tissue. The inevitable derivative of this dogma is that every invasive carcinoma is in fact a missed intraepithelial tumor, and furthermore, a late evolutionary stage in the sequence of development from a precursor lesion. Until fairly recently, high-grade serous ovarian carcinoma seemed to be one of the only known deviants of these concepts. In this article, we discuss the emergence of the fallopian tube fimbria as a field of origin for high-grade serous carcinomas and present a binary model of ovarian cancer pathogenesis that takes into consideration prior epidemiologic, morphologic, and genetic data. With the rise of the fallopian tube secretory epithelial cell as a cell of origin for high-grade pelvic serous carcinomas, the need to develop tools and model systems to characterize the biology and physiology of this cell is recognized.
Receptor Usage and Cell Entry of Porcine Epidemic Diarrhea Coronavirus (2015)

Porcine epidemic diarrhea coronavirus (PEDV) has significantly damaged America's pork industry. Here we investigate the receptor usage and cell entry of PEDV. PEDV recognizes protein receptor aminopeptidase N from pig and human and sugar coreceptor N-acetylneuraminic acid. Moreover, PEDV infects cells from pig, human, monkey, and bat. These results support the idea of bats as an evolutionary origin for PEDV, implicate PEDV as a potential threat to other species, and suggest antiviral strategies to control its spread.
[Study of oxidative stress in the elderly]. (1995)

Determine the oxidative stress status and its significance in elderly subjects.Six parameters marking oxidative stress evaluated in 52 elderly patients (mean age 85 +/- 6 years; range 74 to 98) admitted to a medium-term and long-term nursing home (n = 30) or a hospital ward (n = 22) were compared with those in 30 disease-free young subjects (age range 20-40 years). Plasma levels of thiobarbituric acid reactive substances vitamin E and selenium and activity of free-radical protective enzymes (erythrocyte superoxide dismutase, plasma and erythrocyte glutathione peroxidase) were assessed.Thiobarbituric acid reactive substances were higher and superoxide dismutase, erythrocyte and plasma glutathione peroxidase, and plasma selenium were lower in elderly patients than in young controls. There was no difference in vitamin E levels. In the nursing home population, erythrocyte superoxide dismutase was correlated with erythrocyte glutathione peroxidase and vitamin E, plasma glutathione peroxidase with erythrocyte glutathione peroxidase, vitamin E and selenium and erythrocyte g peroxidase, vitamin E and selenium and erythrocyte glutathione peroxidase with vitamin E. Only the correlation between erythrocyte and plasma glutathione peroxidase was found in the hospitalized population. These levels remained unchanged for a 30 day period in individual patients."Oxidative stress" assessed by six parameters was thus observed in the elderly population and could be considered as a "biological marker of ageing". Supplementation with selenium or other anti-oxidants could be proposed.
PROTEIN TRANSPORT ACROSS THE EUKARYOTIC ENDOPLASMIC RETICULUM AND BACTERIAL INNER MEMBRANES (1996)

Protein transport across the endoplasmic reticulum membrane can occur by two pathways, a co- and a post-translational one. In both cases, polypeptides are first targeted to translocation sites in the membrane by virtue of their signal sequences and then transported across or inserted into the phospholipid bilayer, most likely through a protein-conducting channel. Key components of the translocation apparatus have now been identified and the translocation pathways seem likely to be related to each other but mechanistically distinct. Protein transport across the bacterial inner membrane is both similar to and different from the process in eukaryotes. Other pathways of protein translocation exist that bypass the ones involving classical signal sequences.
Optimal input signals for parameter estimation in dynamic systems--Survey and new results (1974)

This paper surveys the field of optimal input design for parameter estimation as it has developed over the last two decades. Many of the developments covered are only recent and have not appeared in the open literature elsewhere. After a brief introduction, the paper discusses the historical background of the subject both in the engineering and in the statistical literature. The concepts of optimality and input design are then discussed, followed by a derivation of the Fisher information matrix for multiinput multioutput systems with process noise. The design procedures are divided into the categories of time-domain methods and frequency-domain methods, with the former being more general, but also more time consuming (computationally). Several extensions to state constraints, continuous-time systems, etc., are discussed. A number of examples are given to illustrate the nature of optimal inputs. The results on time-domain synthesis with state constraints and their relationship to "dual control" are new.
Humanization of Yeast to Produce Complex Terminally Sialylated Glycoproteins (2006)

Yeast is a widely used recombinant protein expression system. We expanded its utility by engineering the yeast Pichia pastoris to secrete human glycoproteins with fully complex terminally sialylated N-glycans. After the knockout of four genes to eliminate yeast-specific glycosylation, we introduced 14 heterologous genes, allowing us to replicate the sequential steps of human glycosylation. The reported cell lines produce complex glycoproteins with greater than 90% terminal sialylation. Finally, to demonstrate the utility of these yeast strains, functional recombinant erythropoietin was produced.
Low-loss optical demultiplexer for WDM systems in the 08-μm wavelength region (1979)

A low-loss small-sized demultiplexer using a diffraction grating in the Littrow mounting is realized for a wavelength division multiplexing (WDM) system for optical fiber systems. The system has five channels and a wavelength spacing of 200 A in the 0.8-microm region. Insertion loss was about 1.7 dB in each channel, and cross talk was <-30 dB. These characteristics make this demultiplexer the most suitable device available for optical fiber systems employing WDM configurations.
Significance of Macrophage Chemoattractant Protein-1 Expression and Macrophage Infiltration in Squamous Cell Carcinoma of the Esophagusa (2004)

These results suggest that MCP-1 expression and macrophage infiltration is associated with angiogenic promotion in esophageal SCC. MCP-1 expression may be interactively associated with macrophage infiltration in esophageal SCC; MCP-1 may play an important role in tumor angiogenesis through production of angiogenic factors, such as TP, by recruited macrophages in esophageal SCC. Furthermore, CCR-2 expression in vascular endothelial cells may participate partially in angiogenesis. Clinicopathologically, esophageal SCC patients with MCP-1 expression have no favorable prognosis.
Prevention of high salt diet-induced cardiac hypertrophy and fibrosis by spironolactone (2003)

Chronic high salt diet increases LV weight and cardiomyocyte cross-sectional diameter and causes both LV and RV fibrosis. All of these changes are prevented by spironolactone, which is consistent with the concept that cardiac aldosterone mediates these cardiac effects of high salt diet.
Inefficient Signalase Cleavage Promotes Efficient Nucleocapsid Incorporation into Budding Flavivirus Membranes (2003)

The mechanism for efficient nucleocapsid (NC) uptake into flavivirus particles which form by budding through the membranes of the endoplasmic reticulum (ER) was investigated by using Murray Valley encephalitis virus as a model. Budding of flavivirus membranes is driven by the viral transmembrane proteins prM and E independently of NC interaction. We show that control of signalase cleavage of the multimembrane-spanning flavivirus polyprotein by the catalytic function of the viral protease is critical for efficient virus morphogenesis. In wild-type virus, signalase cleavage of prM remains inefficient until cleavage of capsid at the cytosolic side of the signal sequence separating the two proteins has occurred. This obligatory sequence of cleavages was uncoupled in a mutant virus with the consequence of greatly reduced incorporation of NC into budding membranes and augmented release of NC-free virus-like particles. Efficient signalase cleavage of prM in the mutant virus resulted in partial inhibition of cleavage of capsid by the viral NS2B-3 protease. Our results support a model for flavivirus morphogenesis involving temporal and spatial coordination of NC assembly and envelopment by regulated cleavages of an ER membrane-spanning capsid-prM intermediate.
Characterization of VPS34-IN1, a selective inhibitor of Vps34, reveals that the phosphatidylinositol 3-phosphate-binding SGK3 protein kinase is a downstream target of class III phosphoinositide 3-kinase (2014)

The Vps34 (vacuolar protein sorting 34) class III PI3K (phosphoinositide 3-kinase) phosphorylates PtdIns (phosphatidylinositol) at endosomal membranes to generate PtdIns(3)P that regulates membrane trafficking processes via its ability to recruit a subset of proteins possessing PtdIns(3)P-binding PX (phox homology) and FYVE domains. In the present study, we describe a highly selective and potent inhibitor of Vps34, termed VPS34-IN1, that inhibits Vps34 with 25 nM IC50 in vitro, but does not significantly inhibit the activity of 340 protein kinases or 25 lipid kinases tested that include all isoforms of class I as well as class II PI3Ks. Administration of VPS34-IN1 to cells induces a rapid dose-dependent dispersal of a specific PtdIns(3)P-binding probe from endosome membranes, within 1 min, without affecting the ability of class I PI3K to regulate Akt. Moreover, we explored whether SGK3 (serum- and glucocorticoid-regulated kinase-3), the only protein kinase known to interact specifically with PtdIns(3)P via its N-terminal PX domain, might be controlled by Vps34. Mutations disrupting PtdIns(3)P binding ablated SGK3 kinase activity by suppressing phosphorylation of the T-loop [PDK1 (phosphoinositide-dependent kinase 1) site] and hydrophobic motif (mammalian target of rapamycin site) residues. VPS34-IN1 induced a rapid ~50-60% loss of SGK3 phosphorylation within 1 min. VPS34-IN1 did not inhibit activity of the SGK2 isoform that does not possess a PtdIns(3)P-binding PX domain. Furthermore, class I PI3K inhibitors (GDC-0941 and BKM120) that do not inhibit Vps34 suppressed SGK3 activity by ~40%. Combining VPS34-IN1 and GDC-0941 reduced SGK3 activity ~80-90%. These data suggest SGK3 phosphorylation and hence activity is controlled by two pools of PtdIns(3)P. The first is produced through phosphorylation of PtdIns by Vps34 at the endosome. The second is due to the conversion of class I PI3K product, PtdIns(3,4,5)P3 into PtdIns(3)P, via the sequential actions of the PtdIns 5-phosphatases [SHIP1/2 (Src homology 2-domain-containing inositol phosphatase 1/2)] and PtdIns 4-phosphatase [INPP4B (inositol polyphosphate 4-phosphatase type II)]. VPS34-IN1 will be a useful probe to delineate physiological roles of the Vps34. Monitoring SGK3 phosphorylation and activity could be employed as a biomarker of Vps34 activity, in an analogous manner by which Akt is used to probe cellular class I PI3K activity. Combining class I (GDC-0941) and class III (VPS34-IN1) PI3K inhibitors could be used as a strategy to better analyse the roles and regulation of the elusive class II PI3K.
Two distinct fluorescent quantum clusters of gold starting from metallic nanoparticles by pH-dependent ligand etching (2008)

Two fluorescent quantum clusters of gold, namely Au25 and Au8, have been synthesized from mercaptosuccinic acid-protected gold nanoparticles of 4–5 nm core diameter by etching with excess glutathione. While etching at pH ∼3 yielded Au25, that at pH 7–8 yielded Au8. This is the first report of the synthesis of two quantum clusters starting from a single precursor. This simple method makes it possible to synthesize well-defined clusters in gram quantities. Since these clusters are highly fluorescent and are highly biocompatible due to their low metallic content, they can be used for diagnostic applications.
A video system for investigating breathing disorders during sleep. (1991)

A system has been developed for investigating breathing during sleep that superimposes physiological signals on a video image of the patient, with the combined image plus sound recorded on video tape for later analysis. Signals normally displayed include oxygen saturation, airflow, chest wall motion, electroencephalogram, and electrooculogram; but others can be recorded if desired. The information is displayed on a timebase appropriate for the recognition and analysis of respiratory events during sleep. In addition, use is made of normally invisible video lines to record the analogue voltage waveforms so that on replay this information can be displayed on a fast timebase for analysing the more rapidly changing waveforms of electrophysiological signals. The system allows detailed polysomnography to be performed in the normal ward setting with the subject monitored overnight by the nursing staff. Subsequent analysis of the synchronised video, audio, and analogue signals allows measurement of the conventional indices obtained by polysomnography and aids their interpretation.
Selective Solubility of Organometallic Complexes in Saturated Fluorocarbons. Synthesis of Cyclopentadienyl Ligands with Fluorinated Ponytails (1996)

Cyclopentadienes bearing varying length fluorinated “ponytails”, C5H5[(CH2)n(CF2)mF] ([n.m] = [0.8], [0.10], [0.12], [2.6], [2.8], and [2,10]) have been prepared by reaction of the corresponding fluoroalkyl iodides and triphenylphosphine with nickelocene. From these, the 1,1‘-bis[2.6]-, 1,1‘-bis[2.8]-, and 1,1‘-bis[2.10]-disubstituted ferrocenes and [2.10]-substituted [Mn(CO)3L], [Re(CO)3L], and [Co(CO)2L] derivatives (L = η5-C5H4[2.10]) were prepared. Although the anions of the [0.m] compounds were thermally unstable, the corresponding [0.8], [0.10], and [0.12] cobalt dicarbonyl complexes were prepared directly from the cyclopentadienes. The solubilities of these compounds in both saturated fluorocarbon (fluorous) and conventional solvents was found to depend strongly on the length of the fluoroalkyl tail and on the temperature. These compounds all dissolve in fluorous solvents, and the 1,1‘-bis[2.10]ferrocene partitions selectively into the fluorous layer of a biphasic perfluoro(methylcyclohexane)/toluene system. The oxidation potentials of the 1,1‘-, bis[2.6]-, and 1,1‘-bis[2.10]ferrocenes are only very slightly more positive than ferrocene itself, demonstrating that the C2H4 spacer effectively insulates the electron-withdrawing effect of the fluoroalkyl part of the ponytail from the metal. A similar insulating effect is noted in the carbonyl stretching frequencies of [Mn(CO)3L], [Re(CO)3L], and [Co(CO)2L] derivatives (L = η5-C5H4[2.10]), which are slightly to low energy of those in the corresponding parent cyclopentadienyl analogues. In contrast, the corresponding frequencies in [Co(CO)2L] derivatives (L = η5-C5H4[0.10]; η5-C5H4[0.12]) without the hydrocarbon spacer group are at higher energy than the parent compound.
Cancer Drugs Found to Work in New Way (2000)

When it comes to treating cancer with drugs, the dogma is “no pain, no gain.” Patients are hit with doses that may take them within an inch of their lives, then allowed to recover for several weeks before being blasted again. Occasionally, when patients can't tolerate or have already failed to respond to high-dose chemotherapy, oncologists try a gentler chemotherapy regimen: low oral doses taken continuously. Although this approach minimizes side effects and sometimes even shrinks tumors, it does not work well enough to be widely used. Nor has anyone understood its mode of action, especially when it slows down tumors that have already developed resistance to the drug. Now answers are emerging from two new studies in mice, and the information may enable clinicians to improve the effectiveness of this type of therapy.
Induction of Graft-versus-Host Disease as Immunotherapy for Relapsed Chronic Myeloid Leukemia (1994)

The induction of a graft-versus-leukemia reaction with interferon alfa-2b and infusions of donor mononuclear cells in patients with CML in relapse after bone marrow transplantation is an effective antileukemic therapy that may offer an alternative to a second marrow transplantation.
Electron microscopy of a cholesteric liquid crystal and its blue phase (1984)

We report the successful application of the freeze fracture technique for obtaining transmission-electron-microscope pictures of a thermotropic cholesteric material and its blue phase. It is shown that under rapid quenching these phases supercool and conserve their structure at liquid-${\mathrm{N}}_{2}$ temperature. The micrographs obtained confirm the body-centered-cubic symmetry of the blue phase I.
Burst multiplexing method of multimedia signals by commuication terminal (1990)

Abstract This paper proposes a new multimedia burst multiplex system for efficiently multiplexing such multimedia signals as speech and image on the digital channel. The performance is analyzed by approximation. The signals for each medium are encoded, put into packets, and stored in the buffer memory. The controller shared by media monitors the number of packets in the buffer memory as well as the maximum waiting time. The results are weighted for evaluation; and, according to the proposed rule, the packets are sent out to the line. By an approximate analysis, the proposed system is compared with FIFO and another system with priorities. It is seen that the proposed system, in terms of the performance, is in between FIFO and the priority systems. It can control and prioritize according to the property and state of the media, and is suited to multiplexing of media with various properties.
PAF-induced elastase-dependent neutrophil transendothelial migration is associated with the mobilization of elastase to the neutrophil surface and localization to the migrating front (1999)

One of the cardinal signs of acute inflammation is neutrophil (PMN) emigration across the endothelium and into the affected tissue. We have previously shown that human PMN migration across human umbilical vein endothelial cell (HUVEC) monolayers is dependent on PMN-derived elastase. However, whether migrating PMN release elastase into the extracellular milieu or retain it on the cell surface is unclear. In the present study, we show that when PMN are activated by platelet activating factor (PAF), elastase was mobilized to and retained in the cell membrane; no elastase activity was detected in the supernatant. Neutroplasts (enucleated cells devoid of granules) prepared from PAF-activated PMN contained twice as much elastase as did neutroplasts prepared from unstimulated PMN. Neutroplasts from PAF-activated PMN migrated across HUVEC monolayers in response to a chemotactic gradient (PAF), while those prepared from unstimulated PMN did not. The neutroplast transendothelial migration was inhibited (80%) by a monoclonal antibody against elastase. Using confocal microscopy, we noted that the localization of elastase on the cell surface of PMN, which were adherent to HUVEC but not migrating, was largely confined to the apical aspect of the PMN. There was little or no elastase detectable on the basal aspect of the PMN membrane in contact with the endothelium. By contrast, in migrating PMN the membrane-bound elastase was primarily localized to the migrating front, i.e. pseudopodia penetrating the HUVEC monolayers. Taken together, our findings indicate that migrating PMN localize their membrane-bound elastase to the migrating front where it facilitates transendothelial migration.
A single point mutation confers tetrodotoxin and saxitoxin insensitivity on the sodium channel II (1989)

A single point mutation of the rat sodium channel II reduces its sensitivity to tetrodotoxin and saxitoxin by more than three orders of magnitude. The mutation replaces glutamic acid 387 with a glutamine and has only slight effects on the macroscopic current properties, as measured under voltage‐clamp in Xenopus oocytes injected with the corresponding cDNA‐derived mRNA.
Ehrlichia canis-like agent isolated from a man in Venezuela: antigenic and genetic characterization (1996)

We report the first isolation and molecular and antigenic characterization of a human ehrlichial species in South America. A retrospective study was performed with serum specimens from 6 children with clinical signs suggestive of human ehrlichiosis and 43 apparently healthy adults who had a close contact with dogs exhibiting clinical signs compatible with canine ehrlichiosis. The evaluation was performed by the indirect fluorescent-antibody assay with Ehrlichia chaffeensis Arkansas, Ehrlichia canis Oklahoma, and Ehrlichia muris antigens. The sera from two apparently healthy humans were positive by the indirect fluorescent-antibody assay for all three antigens. Of the three antigens, samples from humans 1 and 2 showed the highest antibody titers against E. chaffeensis and E. muris, respectively. The remaining serum samples were negative for all three antigens. One year later examination of a blood sample from subject 1 revealed morulae morphologically resembling either E. canis, E. chaffeensis, or E. muris in monocytes in the blood smear. The microorganism, referred to here as Venezuelan human ehrlichia (VHE), was isolated from the blood of this person at 4 days after coculturing isolated blood leukocytes with a dog macrophage cell line (DH82). The organism was also isolated from mice 10 days after intraperitoneal inoculation of blood leukocytes from subject 1. Analysis by electron microscopy showed that the human isolate was ultrastructurally similar to E. canis, E. chaffeensis, and E. muris. When the virulence of VHE in mice was compared with those of E. chaffeensis, E. canis, and E. muris, only VHE and E. muris induced clinical signs in BALB/c mice at 4 and 10 days, respectively, after intraperitoneal inoculation. VHE was reisolated from peritoneal exudate cells of the mice. Only E. chaffeensis- and E. muris-infected mice developed significant splenomegaly. Western immunoblot analysis showed that serum from subject 1 reacted with major proteins of the VHE antigen of 110, 80, 76, 58, 43, 35, and 34 kDa. Human serum against E. chaffeensis reacted strongly with 58-, 54-, 52-, and 40-kDa proteins of the VHE antigen. Anti-E. canis dog serum reacted strongly with 26- and 24-kDa proteins of VHE. In contrast, anti-E. sennetsu rabbit and anti-E. muris mouse sera did not react with the VHE antigen. Serum from subject 1 reacted with major proteins of 90, 64, or 47 kDa of the E. chaffeensis, E. canis, and E. muris antigens. This reaction pattern suggests that this serum sample was similar to serum samples from E. chaffeensis-infected human patients in Oklahoma. The base sequence of the 16S rRNA gene of VHE was most closely related to that of E. canis Oklahoma. On the basis of these observations, we suggest that VHE is a new strain or a subspecies of E. canis which may cause asymptomatic persistent infection in humans.