gebhart/patrepeval huggingface dataset:
The Production of Amyloid β Peptide Is a Critical Requirement for the Viability of Central Neurons (2003)

The amyloid β peptide (Aβ) is a product of the sequential γ- and β-secretase cleavage of amyloid precursor protein. Inhibitors of secretase enzymes have been proposed as a potential therapeutic strategy in the treatment of Alzheimer's disease. Here, we investigate the effect of inhibiting these key enzymes on the viability of a range of cell types. Treatment of rat cortical neurons for 24 hr with secretase inhibitors or an antibody that binds Aβ resulted in a marked reduction in cell viability, as measured by MTT reduction. Incubation with secretase inhibitors caused similar effects on other neuronal cell types (rat cerebellar granule neurons and the human SH-SY5Y cell line). Interestingly, rat astrocytes and a number of non-neuronal cell lines investigated (HEK293, DDT1-FM2, and human teratorhabdoid tumor cells) were unaffected by incubation with secretase inhibitors. The coincubation of Aβ 1–40 prevented the toxicity of secretase inhibitors in neuronal cells. Aβ 1–40 was protective in a concentration-dependent manner, and its effects were significant at concentrations as low at 10 p m . Importantly, the protective effects of Aβ were Aβ size-form specific, with the Aβ 1–42 size form affording limited protection and the Aβ 25–35 size form having very little protective effect. The present study demonstrates that inhibition of β-or γ-secretase activity induces death in neuronal cells. Importantly, this toxicity, which our data suggest is a consequence of a decline in neuronal Aβ levels, was absent in non-neuronal cells. This study further supports a key physiological role for the enigmatic Aβ peptide.
Progress in palladium-based catalytic systems for the sustainable synthesis of annulated heterocycles: a focus on indole backbones (2012)

A survey highlighting the most recent palladium catalytic systems produced and their performances for progress in direct synthesis of indole backbones by heterocarbocyclization of reactive substrates is provided. The discussion is developed in relation with the principles of sustainable chemistry concerning atom and mass economy. In this respect, the general convergent character of the syntheses is of particular interest (one-pot, domino, cascade or tandem reactions), and the substrates accessibility and reactivity, together with the final waste production, are also important. This critical review clearly indicates that the development of ligand chemistry, mainly phosphines and carbenes, in the last few decades gave a significant impetus to powerful functionalization of indoles at virtually all positions of this ubiquitous backbone (118 references).
A 10000 frames/s CMOS digital pixel sensor (2001)

A 352/spl times/288 pixel CMOS image sensor chip with per-pixel single-slope ADC and dynamic memory in a standard digital 0.18-/spl mu/m CMOS process is described. The chip performs "snapshot" image acquisition, parallel 8-bit A/D conversion, and digital readout at continuous rate of 10000 frames/s or 1 Gpixels/s with power consumption of 50 mW. Each pixel consists of a photogate circuit, a three-stage comparator, and an 8-bit 3T dynamic memory comprising a total of 37 transistors in 9.4/spl times/9.4 /spl mu/m with a fill factor of 15%. The photogate quantum efficiency is 13.6%, and the sensor conversion gain is 13.1 /spl mu/V/e/sup -/. At 1000 frames/s, measured integral nonlinearity is 0.22% over a 1-V range, rms temporal noise with digital CDS is 0.15%, and rms FPN with digital CDS is 0.027%. When operated at low frame rates, on-chip power management circuits permit complete powerdown between each frame conversion and readout. The digitized pixel data is read out over a 64-bit (8-pixel) wide bus operating at 167 MHz, i.e., over 1.33 GB/s. The chip is suitable for general high-speed imaging applications as well as for the implementation of several still and standard video rate applications that benefit from high-speed capture, such as dynamic range enhancement, motion estimation and compensation, and image stabilization.
Palladium- and molybdenum-catalyzed hydrostannation of alkynes. A novel access to regio- and stereodefined vinylstannanes (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPalladium- and molybdenum-catalyzed hydrostannation of alkynes. A novel access to regio- and stereodefined vinylstannanesH. X. Zhang, F. Guibe, and G. BalavoineCite this: J. Org. Chem. 1990, 55, 6, 1857–1867Publication Date (Print):March 1, 1990Publication History Published online1 May 2002Published inissue 1 March 1990https://pubs.acs.org/doi/10.1021/jo00293a035https://doi.org/10.1021/jo00293a035research-articleACS PublicationsRequest reuse permissionsArticle Views6441Altmetric-Citations393LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Regulation of the cell cycle by the cdk2 protein kinase in cultured human fibroblasts. (1993)

In mammalian cells inhibition of the cdc2 function results in arrest in the G2-phase of the cell cycle. Several cdc2-related gene products have been identified recently and it has been hypothesized that they control earlier cell cycle events. Here we have studied the relationship between activation of one of these cdc2 homologs, the cdk2 protein kinase, and the progression through the cell cycle in cultured human fibroblasts. We found that cdk2 was activated and specifically localized to the nucleus during S phase and G2. Microinjection of affinity-purified anti-cdk2 antibodies but not of affinity-purified anti-cdc2 antibodies, during G1, inhibited entry into S phase. The specificity of these effects was demonstrated by the fact that a plasmid-driven cdk2 overexpression counteracted the inhibition. These results demonstrate that the cdk2 protein kinase is involved in the activation of DNA synthesis.
Construction of a Bifunctional mRNA in the Mouse by Using the Internal Ribosomal Entry Site of the Encephalomyocarditis Virus (1992)

Picornaviral mRNAs have been shown to possess special structures in their 5' nontranslated regions (5'NTRs) that provide sites for internal binding of ribosomes and thus direct cap-independent translation. The translational cis-acting elements for ribosomal internal entry into the 5'NTR of encephalomyocarditis virus (EMCV), a member of family Picornaviridae, have been named the internal ribosomal entry site (IRES). All of the published experiments regarding the IRES function of the picornavirus 5'NTR, however, were performed with cell extracts in vitro or with tissue culture cells in transient assay systems. In this study, we examined the IRES function of the EMCV 5'NTR in chimeric mouse embryos and demonstrated that this element does in fact work stably in mouse embryos as well as in embryonic stem (ES) cells. By using a dicistronic vector, pWH8, consisting of a promoter-driven neomycin resistance gene (neo) followed by the EMCV 5'NTR-lacZ sequence, we showed that more than half of the ES cells made G418 resistant by the vector stained positive for beta-galactosidase (beta-gal). On Northern (RNA) blots, all of the clones analyzed revealed a transcript of the expected size containing both the beta-gal and the neo cistrons. These results indicate that dicistronic mRNAs are produced from the stably integrated vector in those ES clones and that both of the cistrons are translated to produce functional proteins. The chimeric embryos derived from these ES clones also stained positive for beta-gal, suggesting that the bifunctional mRNAs are active in the embryos. This dicistronic vector system provides a novel tool by which to obtain temporally and spatially coordinated expression of two different genes driven by a single promoter in a single cell in mice.
The N-terminal Domains of Neuregulin 1 Confer Signal Attenuation (2006)

Degradation of activated ERBB receptors is an important mechanism for signal attenuation. However, compared with epidermal growth factor (EGF) receptor, the ERBB2/ERBB3 signaling pair is considered to be attenuation-deficient. The ERBB2/ERBB3 ligands of the neuregulin family rely on an EGF-like domain for signaling and are generated from larger membrane-bound precursors. In contrast to EGF, which is processed to yield a 6-kDa peptide ligand, mature neuregulins retain a variety of segments N-terminal to the EGF-like domain. Here we evaluate the role of the N-terminal domain of neuregulin 1 in signaling and turnover of ERBB2/ERBB3. Our data suggest that whereas the EGF-like domain of neuregulin 1 is required and sufficient for the formation of active receptor heterodimers, the presence of the N-terminal Ig-like domain is required for efficient signal attenuation. This manifests itself for both ERBB2 and ERBB3 but is more pronounced and coupled directly to degradation for ERBB3. When stimulated with only the EGF-like domain, ERBB3 shows degradation rates comparable with constitutive turnover, but stimulation with full-length neuregulin 1 resulted in receptor degradation at rates that are comparable with activated EGF receptor. Most of the enhancement in down-regulation was maintained after replacing the Ig-like domain with a thioredoxin protein of comparable size but different amino acid composition, suggesting that the physical presence but not specific properties of the Ig-like domain are needed. This sequence-independent effect of the N-terminal domain correlates with an enhanced ability of full-size neuregulin 1 to disrupt higher order oligomers of the ERBB3 extracellular domains in vitro.
Humanizing murine IgG3 anti-GD2 antibody m3F8 substantially improves antibody-dependent cell-mediated cytotoxicity while retaining targeting in vivo (2012)

Murine IgG3 anti-GD2 antibody m3F8 has shown anti-neuroblastoma activity in Phase I/II studies, where antibody-dependent cell-mediated cytotoxicity (ADCC) played a key role. Humanization of m3F8 should circumvent human anti-mouse antibody (HAMA) response and enhance its ADCC properties to reduce dosing and pain side effect. Chimeric 3F8 (ch3F8) and humanized 3F8 (hu3F8-IgG1 and hu3F8-IgG4) were produced and purified by protein A affinity chromatography. In vitro comparison was made with m3F8 and other anti-GD2 antibodies in binding, cytotoxicity, and cross-reactivity assays. In GD2 binding studies by SPR, ch3F8 and hu3F8 maintained K(D) comparable to m3F8. Unlike other anti-GD2 antibodies, m3F8, ch3F8 and hu3F8 had substantially slower k(off.). Similar to m3F8, both ch3F8 and hu3F8 inhibited tumor cell growth in vitro, while cross-reactivity with other gangliosides was comparable to that of m3F8. Both peripheral blood mononuclear cell (PBMC)-ADCC and polymorphonuclear leukocytes (PMN)-ADCC of ch3F8 and hu3F8-IgG1 were more potent than m3F8. This superiority was consistently observed in ADCC assays, irrespective of donors or NK-92MI-transfected human CD16 or CD32, whereas complement mediated cytotoxicity (CMC) was reduced. As expected, hu3F8-IgG4 had near absent PBMC-ADCC and CMC. Hu3F8 and m3F8 had similar tumor-to-non tumor ratios in biodistribution studies. Anti-tumor effect against neuroblastoma xenografts was better with hu3F8-IgG1 than m3F8. In conclusion, humanizing m3F8 produced next generation anti-GD2 antibodies with substantially more potent ADCC in vitro and anti-tumor activity in vivo. By leveraging ADCC over CMC, they may be clinically more effective, while minimizing pain and HAMA side effects. A Phase I trial using hu3F8-IgG1 is ongoing.
Rapid prototyping of microfluidic switches in poly(dimethyl siloxane) and their actuation by electro-osmotic flow (1999)

This paper describes a procedure for rapidly and conveniently prototyping microfluidic devices that are useful with aqueous solutions. A design (with diameters of channels 20 µm) is created in a computer-aided design program and printed at high resolution on a transparency. This transparency is used as a mask in photolithography to create a master in positive relief photoresist: casting poly(dimethyl siloxane) (PDMS) against this master yields a polymeric replica containing a network of bas-relief channels. The channels are closed and sealed irreversibly by oxidizing the replica and another flat substrate (PDMS, glass, silicon, silicon oxide) in an oxygen plasma and bringing the two surfaces into conformal contact. Oxidation of the polymer allows the formation of a seal without using adhesives; it also generates channels that support electro-osmotic flow (EOF) and fill easily with aqueous solutions. Two microfluidic devices - a fluidic switch and a side channel flow controller - have been fabricated using this rapid prototyping methodology. These devices were tested using aqueous solutions as the test fluid and actuated by EOF.
The light field stereoscope (2015)

Over the last few years, virtual reality (VR) has re-emerged as a technology that is now feasible at low cost via inexpensive cellphone components. In particular, advances of high-resolution micro displays, low-latency orientation trackers, and modern GPUs facilitate extremely immersive experiences. To facilitate comfortable long-term experiences and wide-spread user acceptance, however, the vergence-accommodation conflict inherent to all stereoscopic displays will have to be solved. We present the first factored near-eye display technology supporting high image resolutions as well as focus cues --- i.e. accommodation and retinal blur. To this end, we build on Brewster's original stereoscope but augment it with modern factored light field synthesis via stacked liquid crystal panels. We demonstrate significant improvements in resolution and retinal blur quality over previously-proposed near-eye displays.
OpenDMAP: An open source, ontology-driven concept analysis engine, with applications to capturing knowledge regarding protein transport, protein interactions and cell-type-specific gene expression (2008)

OpenDMAP advances the performance standards for extracting protein-protein interaction predications from the full texts of biomedical research articles. Furthermore, this level of performance appears to generalize to other information extraction tasks, including extracting information about predicates of more than two arguments. The output of the information extraction system is always constructed from elements of an ontology, ensuring that the knowledge representation is grounded with respect to a carefully constructed model of reality. The results of these efforts can be used to increase the efficiency of manual curation efforts and to provide additional features in systems that integrate multiple sources for information extraction. The open source OpenDMAP code library is freely available at http://bionlp.sourceforge.net/
Wide viewing angle, homeotropic nematic liquid-crystal display controlled by effective field (1998)

The electro-optic properties of a liquid-crystal display associated with a homeotropic to multidomainlike transition for a liquid crystal with a positive dielectric anisotropy have been investigated. The cell plates are prepared in such a way that, in the absence of an electric field, the liquid-crystal alignment is homeotropic. an electric field created by interdigitated electrodes on both substrates causes a director deformation of a multidomain type. The display shows wide viewing angle, excellent color characteristics, and a fast response time. The molecular director configuration, together with the electro-optic characteristics of the device, are discussed in this letter.
Robust Level Converter for Sub-Threshold/Super-Threshold Operation:100 mV to 2.5 V (2010)

For ultra low power application, digital sub-threshold logic design has been explored. Extremely low power supply (VDD) of sub-threshold logic results in significant power reduction. However, it is difficult to convert signals from core logic to input/output (I/O) circuits since core VDD is vastly different from high I/O supply voltage. In this work, we propose a level converter based on dynamic logic style for sub-threshold I/O part, having a large dynamic range of conversion. For the level converter, high voltage clock signal needs to be delivered through separate clock path from core logic, leading to clock synchronization problem between high voltage and low voltage clocks. To overcome this issue, we employed a Clock Synchronizer. A test chip is fabricated in 130-nm CMOS technology in order to verify the proposed technique. Hardware measurement results show that the level converter successfully converts 0.3 V 8 MHz pulse to 2.5 V signal.
Automatic three-dimensional rib centerline extraction from CT scans for enhanced visualization and anatomical context (2011)

We present a complete automatic system to extract 3D centerlines of ribs from thoracic CT scans. Our rib centerline system determines the positional information for the rib cage consisting of extracted rib centerlines, spinal canal centerline, pairing and labeling of ribs. We show an application of this output to produce an enhanced visualization of the rib cage by the method of Kiraly et al., in which the ribs are digitally unfolded along their centerlines. The centerline extraction consists of three stages: (a) pre-trace processing for rib localization, (b) rib centerline tracing, and (c) post-trace processing to merge the rib traces. Then we classify ribs from non-ribs and determine anatomical rib labeling. Our novel centerline tracing technique uses the Random Walker algorithm to segment the structural boundary of the rib in successive 2D cross sections orthogonal to the longitudinal direction of the ribs. Then the rib centerline is progressively traced along the rib using a 3D Kalman filter. The rib centerline extraction framework was evaluated on 149 CT datasets with varying slice spacing, dose, and under a variety of reconstruction kernels. The results of the evaluation are presented. The extraction takes approximately 20 seconds on a modern radiology workstation and performs robustly even in the presence of partial volume effects or rib pathologies such as bone metastases or fractures, making the system suitable for assisting clinicians in expediting routine rib reading for oncology and trauma applications.
Microbiological changes associated with four different periodontal therapies for the treatment of chronic periodontitis (2008)

The significant reduction of red and orange complex species at 2 weeks in the subjects receiving SRP plus azithromycin or metronidazole may have contributed to a better clinical response in these treatment groups. Therapy did not appear to create lasting changes in the percentage of resistant isolates or sites harboring resistant species.
Characterization of unconventional MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer mice (1997)

Deafness is the most common form of sensory impairment in humans. Mutations in unconventional myosins have been found to cause deafness in humans and mice. The mouse recessive deafness mutation, Snell's waltzer, contains an intragenic deletion in an unconventional myosin, myosin VI (locus designation, Myo6). The requirement for Myo6 for proper hearing in mice makes this gene an excellent candidate for a human deafness disorder. Here we report the cloning and characterization of the human unconventional myosin VI (locus designation, MYO6) cDNA. The MYO6 gene maps to human chromosome 6q13. The isolation of the human gene makes it now possible to determine if mutations in MYO6 contribute to the pathogenesis of deafness in the human population.
Lung cancer * 1: Prevention of lung cancer (2002)

Cancer of the lung causes more deaths from cancer worldwide than at any other site. The environmental, genetic, and dietary risk factors are discussed and progress in chemoprevention is reviewed. A better understanding of the molecular events that occur during carcinogenesis has opened up new areas of research in cancer prevention and a number of biochemical markers of high risk individuals have been identified. It is predicted that greater success in chemoprevention will be achieved in the next decade than in the last.
Noninvasive three-dimensional activation time imaging of ventricular excitation by means of a heart-excitation model (2002)

We propose a new method for imaging activation time within three-dimensional (3D) myocardium by means of a heart-excitation model. The activation time is estimated from body surface electrocardiograms by minimizing multiple objective functions of the measured body surface potential maps (BSPMs) and the heart-model-generated BSPMs. Computer simulation studies have been conducted to evaluate the proposed 3D myocardial activation time imaging approach. Single-site pacing at 24 sites throughout the ventricles, as well as dual-site pacing at 12 pairs of sites in the vicinity of atrioventricular ring, was performed. The present simulation results show that the average correlation coefficient (CC) and relative error (RE) for single-site pacing were 0.9992+/-0.0008/0.9989+/-0.0008 and 0.05+/-0.02/0.07+/-0.03, respectively, when 5 microV/10 microV Gaussian white noise (GWN) was added to the body surface potentials. The average CC and RE for dual-site pacing were 0.9975+/-0.0037 and 0.08+/-0.04, respectively, when 10 microV GWN was added to the body surface potentials. The present simulation results suggest the feasibility of noninvasive estimation of activation time throughout the ventricles from body surface potential measurement, and suggest that the proposed method may become an important alternative in imaging cardiac electrical activity noninvasively.