gebhart/patrepeval huggingface dataset:
Molecular signature of primary retinal pigment epithelium and stem-cell-derived RPE cells (2010)

Age-related macular degeneration (AMD) is characterized by the loss or dysfunction of retinal pigment epithelium (RPE) and is the most common cause of vision loss among the elderly. Stem-cell-based strategies, using human embryonic stem cells (hESCs) or human-induced pluripotent stem cells (hiPSCs), may provide an abundant donor source for generating RPE cells in cell replacement therapies. Despite a significant amount of research on deriving functional RPE cells from various stem cell sources, it is still unclear whether stem-cell-derived RPE cells fully mimic primary RPE cells. In this report, we demonstrate that functional RPE cells can be derived from multiple lines of hESCs and hiPSCs with varying efficiencies. Stem-cell-derived RPE cells exhibit cobblestone-like morphology, transcripts, proteins and phagocytic function similar to human fetal RPE (fRPE) cells. In addition, we performed global gene expression profiling of stem-cell-derived RPE cells, native and cultured fRPE cells, undifferentiated hESCs and fibroblasts to determine the differentiation state of stem-cell-derived RPE cells. Our data indicate that hESC-derived RPE cells closely resemble human fRPE cells, whereas hiPSC-derived RPE cells are in a unique differentiation state. Furthermore, we identified a set of 87 signature genes that are unique to human fRPE and a majority of these signature genes are shared by stem-cell-derived RPE cells. These results establish a panel of molecular markers for evaluating the fidelity of human pluripotent stem cell to RPE conversion. This study contributes to our understanding of the utility of hESC/hiPSC-derived RPE in AMD therapy.
Immunocytochemical localization of the endogenous neuroexcitotoxin quinolinate in human peripheral blood monocytes/macrophages and the effect of human T-cell lymphotropic virus type I infection. (1996)

Quinolinate (Quin), a metabolite in the kynurenine pathway of tryptophan degradation and a neurotoxin that appears to act through the N-methyl-D-aspartate receptor system, was localized in cultured human peripheral blood monocytes/macrophages (PBMOs) by using a recently developed immunocytochemical method. Quin immunoreactivity (Quin-IR) was increased in gamma interferon (IFN-gamma)-stimulated monocytes/macrophages (MOs). In addition, the precursors, tryptophan and kynurenine, significantly increased Quin-IR. Infection of MOs by human T-cell lymphotropic virus type I (HTLV-I) in vitro substantially increased both the number of Quin-IR cells and the intensity of Quin-IR. At the peak of the Quin-IR response, about 40% of the cells were Quin-IR positive. In contrast, only about 2-5% of the cells were positive for HTLV-I, as detected by both immunofluorescence for the HTLV-I antigens and PCR techniques for the HTLV-I Tax gene. These results suggest that HTLV-I-induced Quin production in MOs occurs by an indirect mechanism, perhaps via cytokines produced by the infection but not directly by the virus infection per se. The significance of these findings to the neuropathology of HTLV-I infection is discussed.
Macquarrie, John (b. 1919) (2003)

John Macquarrie is the emeritus Lady Margaret Professor of Divinity at the University of Oxford. He also taught at Union Theological Seminary in New York City. His work played a leading role in interpreting Christianity in terms of existentialism in the twentieth century.For Macquarrie, Jesus Christ
Studies on the Effects of Antioxidants and Inhibitors of Radical Generation on Free Radical Production in the Reperfused Rat Heart Using Electron Spin Resonance Spectroscopy (1990)

Reperfusion of the heart after a period of ischaemia can precipitate ventricular arrhythmias and lead to an exacerbation of tissue injury. Direct evidence to suggest the involvement of free radicals has been obtained using electron spin resonance (esr) spectroscopy and the spin trap N-tert. butyl-alpha-phenyl nitrone (PBN). In the present study, we have used esr spectroscopy and PBN to examine the individual effects of superoxide dismutase (SOD), catalase, allopurinol or desferal on radical production in the isolated, reperfused rat heart. A burst of radical production was observed in the control group during the first 5 minutes of reperfusion; the peak occurred during the first minute, when signal intensity had increased by almost 300%, but returned to the baseline by 15 minutes of reperfusion. The esr signals were consistent with the trapping of either alkoxyl or carbon-centered radicals (aN = 13.6 and aH = 1.56 G). In the desferal-treated group, a burst of radical production was observed during the first five minutes of reperfusion; this was maximal during the second minute, when signal intensity had increased by almost 200%, but had returned to the baseline value by 30 minutes of reperfusion. In the SOD-treated group, a burst of radical production was observed during the first 10 minutes of reperfusion; signal intensity was maximal during the tenth minute of reperfusion, when signal intensity had increased by almost 200%, but had returned to the baseline value by 30 minutes of reperfusion. In the allopurinol- and catalase-treated groups, no significant burst of radical production could be detected. These data further support the concept that cytotoxic, oxygen-derived species are formed upon reperfusion and that hydrogen peroxide and/or hydroxyl radicals, are likely to be involved.
Biochemical and molecular characterization of senescence‐related cysteine protease–cystatin complex from spinach leaf (2010)

Cysteine proteases (CPs) with N-succinyl-Leu-Tyr-4-methylcoumaryl-7-amide (Suc-LY-MCA) cleavage activity were investigated in green and senescent leaves of spinach. The enzyme activity was separated into two major and several faint minor peaks by hydrophobic chromatography. These peaks were conventionally designated as CP1, CP2 and CP3, according to their order of elution. From the analyses of molecular mass, subunit structure, amino acid sequences and cDNA cloning, CP2 was a monomer complex (SoCP-CPI) (51 kDa) composed of a 41-kDa core protein, SoCP (Spinacia oleracea cysteine protease), and 14-kDa cystatin, a cysteine protease inhibitor (CPI), while CP3 was a trimer complex (SoCP-CPI)(3) (151 kDa) of the same subunits as SoCP-CPI and showed a wider range of specificity toward natural substrates than SoCP-CPI. Trimer (SoCP-CPI)(3) was irreversibly formed from monomers through association. The results of reverse transcription-polymerase chain reaction (RT-PCR) revealed that mRNAs of CPI and SoCP are hardly expressed in green leaves, but they are coordinately expressed in senescent leaves, suggesting that these proteases involve in senescence. Purified recombinant CPI had strong inhibitory activity against trimer SoCP, (SoCP)(3) , which had a cystatin deleted with K(i) value of 1.33 × 10(-9) M. After treatment of the enzyme with a succinate buffer (pH 5) at the most active pH of the enzyme, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and activity analyses showed that cystatin was released from both monomer SoCP-CPI and trimer (SoCP-CPI)(3) complexes with a concomitant activation. Thus, the removal of a cystatin is necessary to activate the enzyme activity.
Strigolactone Analogs Derived from Ketones Using a Working Model for Germination Stimulants as a Blueprint (2011)

Strigolactones are important signaling compounds in the plant kingdom. Here we focus on their germination stimulatory effect on seeds of the parasitic weeds Striga and Orobanche spp. and more particularly on the design and synthesis of new active strigolactone analogs derived from simple cyclic ketones. New analogs derived from 1-indanone, 1-tetralone, cyclopentanone, cyclohexanone and a series of substituted cyclohexanones (including carvone and pulegone) are prepared by formylation of the ketones with ethyl formate followed by coupling with a halo butenolide. Both enantiomers of the analog derived from 1-tetralone have been prepared by employing a homochiral synthon for the coupling reaction. For three other strigolactone analogs the antipodes have been obtained by chromatography on a chiral column. All analogs have an appreciable germinating activity towards seeds of Striga hermomonthica and Orobanche crenata and O. cernua. Stereoisomers having the same configuration at the D-ring as in naturally occurring strigol have a higher stimulatory effect than the corresponding antipodes. The analogs obtained from 1-indanone and 1-tetralone have an activity comparable with that of the well known stimulant GR 24. Analogs derived from 2-phenyl-cylohexanone, carvone and pulegone also have a good germinating response. The results show that the working model for designing new bioactive strigolactones is applicable.
TOWARDS AN INDUSTRIAL FABRICATION PROCESS FOR ELECTROWETTING CHIP USING STANDARD MEMS TECHNOLOGY (2008)

Reliability of Electrowetting on Dielectric (EWOD) microsystems partly relies on the hydrophobic layer. A process for depositing a SIOC (organosiloxane molecule) material fitting all the needs was firstly established on a laboratory equipment, then further transferred on an industrial machine devoted to microelectronics fabrication. For packaging purposes, this layer has to be patterned on the EWOD chip. A lift-off process was investigated and showed promising results. Simplifying the packaging steps is essential for a rapid cycle fabrication to test. In this way, an experimental setup was developed in order to directly make electrical contact on the EWOD chip.
Photoaffinity Labeling of the Human Receptor for Urokinase-Type Plasminogen Activator Using a Decapeptide Antagonist. Evidence for a Composite Ligand-Binding Site and a Short Interdomain Separation (1998)

Binding of urokinase-type plasminogen activator (uPA) to its cellular receptor (uPAR) renders the cell surface a favored site for plasminogen activation. Recently, a 15-mer peptide antagonist of the uPA-uPAR interaction, with an IC50 value of 10 nM, was identified using phage display technology [Goodson, R. J., Doyle, M. V., Kaufman, S. E., and Rosenberg, S. (1994) Proc. Natl. Acad. Sci. 91, 7129-7133]. In the present study, the molecular aspects of the interaction between this peptide and uPAR have been investigated. We have characterized the real-time receptor binding kinetics for the antagonist using surface plasmon resonance and identified critical residues by alanine replacements. The minimal peptide antagonist thus derived (SLNFSQYLWS) was rendered photoactivatable by replacing residues important for uPAR binding with photochemically active derivatives of phenylalanine containing either (trifluoromethyl)diazirine or benzophenone. These peptides incorporated covalently into purified soluble uPAR upon photoactivation, and this was inhibited by preincubation with receptor binding derivatives of uPA. The intact three-domain structure of uPAR was essential for efficient photoaffinity labeling. Proteolytic domain mapping using chymotrypsin revealed a specific labeling of both uPAR domain I and domains II + III dependent on the position of the photoprobe in the antagonist. On the basis of these studies, we propose the existence of a composite ligand binding site in uPAR combined of residues located in distinct structural domains. According to this model, a close spatial proximity between uPAR domain I and either domains II or III in intact uPAR is required for the assembly of this composite binding site. Since the receptor binding properties of the peptide antagonist closely mimic those of uPA itself, these two ligands presumably share coincident binding site in uPAR.
Rescue of an influenza A virus wild-type PB2 gene and a mutant derivative bearing a site-specific temperature-sensitive and attenuating mutation (1993)

Live attenuated influenza A virus vaccines are currently produced by the transfer of attenuating genes from a donor virus to new epidemic variants of influenza A virus, with the selection of reassortant viruses that possess the protective antigens (i.e., the two surface glycoproteins) of the epidemic virus and the attenuating genes from the donor virus. The previously studied attenuated donor viruses were produced by conventional methods such as passage of virus at low temperature or chemical mutagenesis. The present paper describes a new strategy for the generation of a donor virus bearing an attenuating, non-surface-glycoprotein gene. This strategy involves the introduction of attenuating mutations into the cDNA copy of the PB2 polymerase gene by site-directed mutagenesis, transfection of in vitro RNA transcripts of PB2 cDNA, and recovery of the transfected PB2 gene into an infectious virus. An avian-human influenza A virus PB2 single-gene reassortant virus (with an avian influenza A virus PB2 gene) that replicates efficiently in avian tissue but poorly in mammalian cells was used as a helper virus to rescue a transfected synthetic RNA derived from a human influenza A virus PB2 gene. The desired human influenza A virus mutant PB2 transfectant was favored in this situation because the avian influenza A virus PB2 gene restricts viral replication in mammalian cells in culture, the system used for rescue, thereby providing strong selection for the virus bearing the human influenza A virus PB2 gene. We validated the feasibility of this approach by rescuing the PB2 gene of the wild-type influenza A/Ann Arbor/6/60 virus and a mutant derivative that had a single amino acid substitution introduced at position 265 by site-directed mutagenesis. Previously, this amino acid substitution had been shown to specify both a temperature-sensitive (ts) and an attenuation (att) phenotype. The rescued mutant 265 PB2 transfectant virus exhibited the ts and att phenotypes, which confirms that these phenotypes were specified by this single amino acid substitution. The transfectant virus was immunogenic and protected hamsters from subsequent challenge with wild-type virus. The cDNA copy of this influenza A/Ann Arbor/6/60 virus mutant 265 PB2 gene will be used as a substrate for the introduction of additional attenuating mutations by site-directed mutagenesis.
Virtual Reality simulator for dental anesthesia training in the inferior alveolar nerve block (2017)

The simulation was considered thoroughly satisfactory for the anesthesia training, considering the needle insertion task, which includes the correct insertion point and depth, as well as the perception of tissues resistances during the insertion.
Analysis of ion-implanted amorphous and polycrystalline silicon films as diffusion sources for ultrashallow junctions (1991)

This paper discusses the diffusion of As, P, and B in amorphous and polycrystalline silicon-on-single-crystal silicon systems during rapid thermal annealing and furnace annealing. It is found that the changes of microstructure during annealing play a major role in determining the diffusion profiles in the substrate as well as in the polycrystalline silicon layer. For As or P doping, a drive-in diffusion results in a much larger grain microstructure for as-deposited amorphous silicon than for as-deposited polycrystalline silicon, which leads to the formation of shallower junctions in the substrate for the first case. For B doping, there is little difference in the final microstructure and junction depth between the two cases. At high anneal temperatures, the native interfacial oxide breaks up, causing epitaxial realignment of the polycrystalline silicon film and subsequent enhanced diffusion in the substrate.
Discrete all-pole modeling (1991)

A method for parametric modeling and spectral envelopes when only a discrete set of spectral points is given is introduced. This method, called discrete all-pole (DAP) modeling, uses a discrete version of the Itakura-Saito distortion measure as its error criterion. One result is an autocorrelation matching condition that overcomes the limitations of linear prediction and produces better fitting spectral envelopes for spectra that are representable by a relatively small discrete set of values, such as in voiced speech. An iterative algorithm for DAP modeling that is shown to converge to a unique global minimum is presented. Results of applying DAP modeling to real and synthetic speech are also presented. DAP modeling is extended to allow frequency-dependent weighting of the error measure, so that spectral accuracy can be enhanced in certain frequency regions.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Klf4 Regulates the Expression of Slurp1, Which Functions as an Immunomodulatory Peptide in the Mouse Cornea (2012)

Klf4 regulates the expression of Slurp1, a key immunomodulatory peptide that is abundantly expressed in healthy corneas and is downregulated in proinflammatory conditions.
Waveguide electrooptic switch arrays (1988)

A review is presented of electrooptic waveguide switch arrays with strong emphasis on those based on titanium-diffused lithium niobate waveguides. Crosspoint and array design considerations and performance are discussed as are waveguide technology limits. Switch array demonstrations are reviewed. Experimental demonstrations of switch arrays are described and particular parameters of the array, including insertion loss, crosstalk, and switching voltage achieved by several laboratories, are discussed and compared. Results of high-speed switch arrays are also described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
COTD: Reference-Free Hardware Trojan Detection and Recovery Based on Controllability and Observability in Gate-Level Netlist (2016)

This paper presents a novel hardware Trojan detection technique in gate-level netlist based on the controllability and observability analyses. Using an unsupervised clustering analysis, the paper shows that the controllability and observability characteristics of Trojan gates present significant inter-cluster distance from those of genuine gates in a Trojan-inserted circuit, such that Trojan gates are easily distinguishable. The proposed technique does not require any golden model and can be easily integrated into the current integrated circuit design flow. Furthermore, it performs a static analysis and does not require any test pattern application for Trojan activation either partially or fully. In addition, the timing complexity of the proposed technique is an order of the number of signals in a circuit. Moreover, the proposed technique makes it possible to fully restore an inserted Trojan and to isolate its trigger and payload circuits. The technique has been applied on various types of Trojans, and all Trojans are successfully detected with 0 false positive and negative rates in less than 14 s in the worst case.
Simple and low cost fabrication of embedded micro-channels by using a new thick-film photoplastic (2002)

In this paper we describe new ways to realise micro-channels. The used technologies are based on a novel thick-film photoplastic, the SU-8. This photoresist has outstanding properties, allowing the realisation of high aspect ratio microstructures. It is a simple and low-cost fabrication process. The micro channels developed in this work will be used for the realisation of thermal flow-sensors.
Determination of Equilibrium Constants for Atom Transfer Radical Polymerization (2006)

Atom transfer radical polymerization (ATRP) equilibrium constants (K(ATRP)) were determined using modified Fischer's equations for the persistent radical effect. The original Fischer's equations could be used only for low conversion of Cu(I) to X-Cu(II) and consequently for relatively low values of K(ATRP). At higher conversion to X-Cu(II) (>10%) and for larger values of K(ATRP) (>10(-)(7)), modified equations that take into account the changes in catalyst and initiator concentrations should be used. The validity of new equations was confirmed by detailed kinetic simulations. UV-vis spectrometric and GC measurements were used to follow the evolution of X-Cu(II) species and the initiator concentration, respectively, and to successfully determine values of K(ATRP) for several catalysts and alkyl halides. The effect of structure on reactivities of ATRP components is presented.
Nasal polyposis (2012)

There is mounting evidence for CRSwNP as a predominantly inflammatory disease. Even simple histopathological classification on the basis of degrees of tissue eosinophilia reflects the underlying pathogenic mechanisms with diagnostic and prognostic implications. Optimal treatment involves topical anti-inflammatory therapy delivered locally via a wide, postsurgical corridor.
Xanthomonas AvrBs3 Family-Type III Effectors: Discovery and Function (2010)

Xanthomonads are bacterial plant pathogens that cause diseases on many plant species, including important crops. Key to pathogenicity of most Xanthomonas pathovars is a Hrp-type III secretion (T3S) system that translocates effector proteins into plant cells. Within the eukaryotic cell, the effectors are thought to perform a variety of tasks to support bacterial virulence, proliferation, and dissemination. We are only beginning to understand the host targets of different effectors. The largest effector family found in Xanthomonas spp. is the AvrBs3/PthA or TAL (transcription activator-like) family. TAL effectors act as transcriptional activators in the plant cell nucleus. Specificity of TAL effectors is determined by a novel modular DNA-binding domain. Here, we describe the discovery of TAL effectors and their structure, activity, and host targets.
Safety and biomarker effects of solanezumab in patients with Alzheimer's disease (2012)

Antibody administration was well tolerated with doses up to 400 mg weekly. The dose-dependent increase in unbound CSF Aβ(1-42) suggests that this antibody may shift Aβ equilibria sufficiently to mobilize Aβ(1-42) from amyloid plaques.
Microglial p38α MAPK is critical for LPS-induced neuron degeneration, through a mechanism involving TNFα (2011)

The data suggest that selective targeting of p38α MAPK signaling should be explored as a potential therapeutic strategy for CNS disorders where overproduction of proinflammatory cytokines is implicated in disease progression.
Current Role of Lipoprotein Apheresis in the Treatment of High-Risk Patients (2018)

Lipoprotein apheresis (LA) is a therapeutic approach to save the lives of patients who are at an extremely high risk of developing cardiovascular events (CVE), especially after all other therapeutic options were not tolerated, or appeared not to be effective enough. Homozygous familial hypercholesterolemia represents a clear indication to start LA therapy. Another recognized indication is a severe hypercholesterolemia, which induced CVE, often in association with other risk factors. In the last years, an expressive elevation of lipoprotein(a) (Lp(a)) emerged as an indication for LA. In Germany, progress of atherosclerosis should have been documented before the permission to start LA therapy is given in these patients. Usually, all LA methods acutely decrease both LDL-C and Lp(a). However, specific columns which reduce only Lp(a) are available. Case reports and prospective observations comparing the situation before and during LA therapy clearly show a high efficiency with respect to the reduction of CVE, especially in patients with high Lp(a) levels. PCSK9 inhibitors may reduce the need for LA in patients with heterozygous or polygenetic hypercholesterolemia, but in some patients, a combination of these drugs with LA will be necessary. In the future, an antisense oligonucleotide against apolipoprotein(a) may offer an alternative therapeutic approach.