gebhart/patrepeval huggingface dataset:
2′-Deoxy-4′-azido Nucleoside Analogs Are Highly Potent Inhibitors of Hepatitis C Virus Replication Despite the Lack of 2′-α-Hydroxyl Groups (2007)

RNA polymerases effectively discriminate against deoxyribonucleotides and specifically recognize ribonucleotide substrates most likely through direct hydrogen bonding interaction with the 2'-alpha-hydroxy moieties of ribonucleosides. Therefore, ribonucleoside analogs as inhibitors of viral RNA polymerases have mostly been designed to retain hydrogen bonding potential at this site for optimal inhibitory potency. Here, two novel nucleoside triphosphate analogs are described, which are efficiently incorporated into nascent RNA by the RNA-dependent RNA polymerase NS5B of hepatitis C virus (HCV), causing chain termination, despite the lack of alpha-hydroxy moieties. 2'-deoxy-2'-beta-fluoro-4'-azidocytidine (RO-0622) and 2'-deoxy-2'-beta-hydroxy-4'-azidocytidine (RO-9187) were excellent substrates for deoxycytidine kinase and were phosphorylated with efficiencies up to 3-fold higher than deoxycytidine. As compared with previous reports on ribonucleosides, higher levels of triphosphate were formed from RO-9187 in primary human hepatocytes, and both compounds were potent inhibitors of HCV virus replication in the replicon system (IC(50) = 171 +/- 12 nM and 24 +/- 3 nM for RO-9187 and RO-0622, respectively; CC(50) >1 mM for both). Both compounds inhibited RNA synthesis by HCV polymerases from either HCV genotypes 1a and 1b or containing S96T or S282T point mutations with similar potencies, suggesting no cross-resistance with either R1479 (4'-azidocytidine) or 2'-C-methyl nucleosides. Pharmacokinetic studies with RO-9187 in rats and dogs showed that plasma concentrations exceeding HCV replicon IC(50) values 8-150-fold could be achieved by low dose (10 mg/kg) oral administration. Therefore, 2'-alpha-deoxy-4'-azido nucleosides are a new class of antiviral nucleosides with promising preclinical properties as potential medicines for the treatment of HCV infection.
Use of a heated graphite scrubber as a means of reducing interferences in UV-absorbance measurements of atmospheric ozone (2017)

Abstract. A new solid-phase scrubber for use in conventional ozone (O3) photometers was investigated as a means of reducing interferences from other UV-absorbing species and water vapor. It was found that when heated to 100–130 °C, a tubular graphite scrubber efficiently removed up to 500 ppb ozone and ozone monitors using the heated graphite scrubber were found to be less susceptible to interferences from water vapor, mercury vapor, and aromatic volatile organic compounds (VOCs) compared to conventional metal oxide scrubbers. Ambient measurements from a graphite scrubber-equipped photometer and a co-located Federal equivalent method (FEM) ozone analyzer showed excellent agreement over 38 days of measurements and indicated no loss in the scrubber's ability to remove ozone when operated at 130 °C. The use of a heated graphite scrubber was found to reduce the interference from mercury vapor to ≤ 3 % of that obtained using a packed-bed Hopcalite scrubber. For a series of substituted aromatic compounds (ranging in volatility and absorption cross section at 253.7 nm), the graphite scrubber was observed to consistently exhibit reduced levels of interference, typically by factors of 2.5 to 20 less than with Hopcalite. Conventional solid-phase scrubbers also exhibited complex VOC adsorption and desorption characteristics that were dependent upon the relative humidity (RH), volatility of the VOC, and the available surface area of the scrubber. This complex behavior involving humidity is avoided by use of a heated graphite scrubber. These results suggest that heated graphite scrubbers could be substituted in most ozone photometers as a means of reducing interferences from other UV-absorbing species found in the atmosphere. This could be particularly important in ozone monitoring for compliance with the United States (U.S.) Clean Air Act or for use in VOC-rich environments such as in smog chambers and monitoring indoor air quality.
<title>Automatic defect classification for integrated circuits</title> (1993)

While initial detection of defects is the most critical function of inspection, automatic classification of detected defects is becoming increasingly desirable. The key to better process control is reliable process measurement. The classification of defects provides valuable process diagnosis information. The hope is that machines can perform this task more reliably than humans. However, there are many problems in automating defect classification, and many of these are related to the central problems in artificial intelligence, such as knowledge representation, inferencing, and dealing with uncertainty. In this paper we pay special attention to the issues arising in the Automatic Defect Classification (ADC) of integrated circuits. We first discuss technical and system requirements, followed by an outline of the technical challenges to be overcome to develop flexible and powerful ACD tools which can be quickly customized on a user level for diverse applications.
Analysis of an optically controlled photonic switch (1999)

The principle that the coupling of light between two fiber waveguides can be controlled by the resonant interference of a third waveguide has been developed [Attard, Appl. Opt. 37, 2296-2302 (1998)]. Here significant details concerning the operation of a photonic switch are obtained, and a more complete analysis is presented. Multiple-resonant conditions are identified for slab and fiber control waveguides at large indices of refraction. Thus a selection of materials with an appropriate refractive index and a Kerr coefficient is rendered more easily. Furthermore it is shown that the light used to control the index of refraction in the control waveguide does not enter the output of the photonic switch but remains confined to the control waveguide, for either a slab or a multimode fiber control waveguide. Spatial fluctuations of the control light beam in the control waveguide do not affect the operation of the photonic switch. Tolerances have been determined for the spacing between the control waveguide and the photonic coupler and also for the index of refraction of the control waveguide.
Oligomerization of G-Protein-Coupled Receptors: Lessons from the Yeast<i>Saccharomyces cerevisiae</i> (2005)

G-protein-coupled receptors (GPCR) signaling is an evolutionarily ancient mechanism used by all eukaryotes to sense environmental stimuli and mediate cell-cell communication (7,28).During evolution, GPCR genes expanded enormously in number and diversity.Whereas only three of the ϳ5,900 genes in the yeast Saccharomyces cerevisiae encode GPCRs, at least 55 of the ϳ12,000 genes in Dictyostelium encode GPCRs (19), and more than 1,000 of the ϳ22,000 genes in humans encode receptors of this class (28).GPCRs are of crucial physiologic importance.In eukaryotic microorganisms, GPCRs regulate cell growth, development, morphogenesis, motility, and life span.In humans they mediate the action of hundreds of peptide hormones, sensory stimuli, autacoids, neurotransmitters, and chemokines.GPCRs also are targets of many clinically important drugs as well as drugs of abuse.Despite exhibiting striking diversity in primary sequence and biologic function, GPCRs possess the same fundamental architecture, consisting of seven transmembrane (TM) domains and share common mechanisms of signal transduction (85).GPCRs transduce extracellular signals by coupling to heterotrimeric guanine nucleotide binding proteins (G proteins) consisting of ␣, ␤, and ␥ subunits.Activated GPCRs stimulate exchange of GTP for GDP on G␣ subunits, dissociating G␣ and G␤␥ subunits that, in turn, trigger biological responses by binding effector proteins that regulate second messenger production, protein kinase cascades, cytoskeletal organization, gene transcription, and ion channel activity.GPCRs also signal by G protein-independent mechanisms through recruitment of scaffold proteins such as ␤-arrestins (reviewed in reference 54).In the budding yeast S. cerevisiae, GPCR signaling regulates two biologic processes: conjugation and nutrient sensing (reviewed in references 15 and 106).During conjugation, a mating type cells secrete a-factor, a 12-residue farnesylated oligopeptide pheromone that binds the G-protein-coupled a-factor receptor (STE3 gene product) expressed only by cells of the ␣ mating type.Conversely, ␣ cells secrete ␣-factor, an unmodified 13-residue peptide pheromone that binds the Gprotein-coupled ␣-factor receptor (STE2 gene product) expressed only by cells of the a mating type.Although a-and ␣-factor receptors are unrelated in primary sequence, they
Motility contrast imaging of live porcine cumulus-oocyte complexes (2013)

Freshly-harvested porcine oocytes are invested with cumulus granulosa cells in cumulus-oocyte complexes (COCs). The cumulus cell layer is usually too thick to image the living oocyte under a conventional microscope. Therefore, it is difficult to assess the oocyte viability. The low success rate of implantation is the main problem for in vitro fertilization. In this paper, we demonstrate our dynamic imaging technique called motility contrast imaging (MCI) that provides a non-invasive way to monitor the COCs before and after maturation. MCI shows a change of intracellular activity during oocyte maturation, and a measures dynamic contrast between the cumulus granulosa shell and the oocytes. MCI also shows difference in the spectral response between oocytes that were graded into quality classes. MCI is based on shortcoherence digital holography. It uses intracellular motility as the endogenous imaging contrast of living tissue. MCI presents a new approach for cumulus-oocyte complex assessment.
DNA Extraction on Microfluidic Devices. (2010)

Purification of DNA is a critical step of the genetic analysis process, particularly when the interrogation of forensic samples, often contaminated by exogenous and endogenous inhibitors, is considered. Recently, examples of microfluidic DNA purification strategies are becoming more prolific, with successful extraction of DNA from a variety of forensically relevant targets demonstrated using these microscale techniques and systems. From silica-based purification strategies that mimic their macroscale counterparts, to novel functionally derivatized systems, these purification tools represent the newest schemes for rapid, automated, closed-system sample processing that can integrate seamlessly with downstream microscale analysis techniques. The work presented herein highlights the development of novel microscale purification systems for extraction of DNA, their potential application in forensic analysis, and their potential for future incorporation in micro total analysis systems (µTAS).
Excimer Lasers: Current Trends And Future Directions (1989)

This paper discusses the design and performance of a new excimer laser. The laser delivers output powers as high as 160 Watts on KrF with an efficiency of 4.5%, and has demonstrated gas lifetimes significantly better than any previously reported for high-power, commercial lasers. Details are given of an apparatus designed to determine the impurities which presently limit gas lifetime in excimer lasers.
A pH‐Neutral, Metal‐Free Aqueous Organic Redox Flow Battery Employing an Ammonium Anthraquinone Anolyte (2019)

Abstract Redox‐active anthraquinone molecules represent promising anolyte materials in aqueous organic redox flow batteries (AORFBs). However, the chemical stability issue and corrosion nature of anthraquinone‐based anolytes in reported acidic and alkaline AORFBs constitute a roadblock for their practical applications in energy storage. A feasible strategy to overcome these issues is migrating to pH‐neutral conditions and employing soluble AQDS salts. Herein, we report the 9,10‐anthraquinone‐2,7‐disulfonic diammonium salt AQDS(NH 4 ) 2 , as an anolyte material for pH‐neutral AORFBs with solubility of 1.9 m in water, which is more than 3 times that of the corresponding sodium salt. Paired with an NH 4 I catholyte, the resulting pH‐neutral AORFB with an energy density of 12.5 Wh L −1 displayed outstanding cycling stability over 300 cycles. Even at the pH‐neutral condition, the AQDS(NH 4 ) 2 /NH 4 I AORFB delivered an impressive energy efficiency of 70.6 % at 60 mA cm −2 and a high power density of 91.5 mW cm −2 at 100 % SOC. The present AQDS(NH 4 ) 2 flow battery chemistry opens a new avenue to apply anthraquinone molecules in developing low‐cost and benign pH‐neutral flow batteries for scalable energy storage.
Flawless Diamond Reconstruction for Simultaneous Source Separation (2017)

Summary In this paper we prove that the recently introduced method of signal apparition optimally separates signals from interfering sources recorded during simultaneous source seismic data acquisition. By utilizing a periodic sequence of source signatures along one source line, that wavefield becomes separately partially visible in the spectral domain where it can be isolated from interfering signals, processed, and subtracted from the original recordings, thereby separating the wavefields from each other. Whereas other methods for simultaneous source separation can recover data in triangle-shaped region in the spectral domain, signal apparition allows for the exact separation of data in a diamond-shaped region that is twice as large thereby enabling superior reconstruction of separated wavefields throughout the entire data bandwidth.
Viral Nanoparticles for <em>In vivo</em> Tumor Imaging (2012)

The use of nanomaterials has the potential to revolutionize materials science and medicine. Currently, a number of different nanoparticles are being investigated for applications in imaging and therapy. Viral nanoparticles (VNPs) derived from plants can be regarded as self-assembled bionanomaterials with defined sizes and shapes. Plant viruses under investigation in the Steinmetz lab include icosahedral particles formed by Cowpea mosaic virus (CPMV) and Brome mosaic virus (BMV), both of which are 30 nm in diameter. We are also developing rod-shaped and filamentous structures derived from the following plant viruses: Tobacco mosaic virus (TMV), which forms rigid rods with dimensions of 300 nm by 18 nm, and Potato virus X (PVX), which form filamentous particles 515 nm in length and 13 nm in width (the reader is referred to refs. 1 and 2 for further information on VNPs). From a materials scientist's point of view, VNPs are attractive building blocks for several reasons: the particles are monodisperse, can be produced with ease on large scale in planta, are exceptionally stable, and biocompatible. Also, VNPs are "programmable" units, which can be specifically engineered using genetic modification or chemical bioconjugation methods 3. The structure of VNPs is known to atomic resolution, and modifications can be carried out with spatial precision at the atomic level4, a level of control that cannot be achieved using synthetic nanomaterials with current state-of-the-art technologies. In this paper, we describe the propagation of CPMV, PVX, TMV, and BMV in Vigna ungiuculata and Nicotiana benthamiana plants. Extraction and purification protocols for each VNP are given. Methods for characterization of purified and chemically-labeled VNPs are described. In this study, we focus on chemical labeling of VNPs with fluorophores (e.g. Alexa Fluor 647) and polyethylene glycol (PEG). The dyes facilitate tracking and detection of the VNPs 5-10, and PEG reduces immunogenicity of the proteinaceous nanoparticles while enhancing their pharmacokinetics 8,11. We demonstrate tumor homing of PEGylated VNPs using a mouse xenograft tumor model. A combination of fluorescence imaging of tissues ex vivo using Maestro Imaging System, fluorescence quantification in homogenized tissues, and confocal microscopy is used to study biodistribution. VNPs are cleared via the reticuloendothelial system (RES); tumor homing is achieved passively via the enhanced permeability and retention (EPR) effect12. The VNP nanotechnology is a powerful plug-and-play technology to image and treat sites of disease in vivo. We are further developing VNPs to carry drug cargos and clinically-relevant imaging moieties, as well as tissue-specific ligands to target molecular receptors overexpressed in cancer and cardiovascular disease.
A persistent double-strand break destabilizes human DNA in yeast and can lead to G2 arrest and lethality. (1997)

Double-strand breaks (DSBs) are an important source of genomic change in many organisms. We have examined the consequences of a persistent versus a rapidly repaired DSB on cell progression, viability, and stability of human DNA contained in dispensable yeast artificial chromosomes (YACs) within the yeast Saccharomyces cerevisiae. An Alu-URA3-YZ integrating plasmid was used to target the YZ sequence to repetitive Alu sequences within the human YAC. The YZ site can be cut by an inducible HO-endonuclease resulting in a DSB. Two classes of DSBs had been identified previously: those that could be rapidly repaired (RR-DSB), through recombination between flanking Alus; and persistent DSBs (C. B. Bennett et al., Mol. Cell. Biol., 16: 4414-4425, 1996). These persistent DSBs (type 1) resulted in G2 delay and lethality. A third class of DSB is now identified corresponding to a persistent DSB that does not lead to G2 arrest or lethality (type 2). Unlike YACs in which the DSB was rapidly repaired, the two types of persistent DSBs destabilized the human YAC DNA, resulting in a high likelihood of YAC loss (approximately 85% of surviving colonies). Furthermore, both types of persistent DSBs could be misrepaired, resulting in mostly large internal or terminal deletions in the retained YACs. Therefore, recovery of these altered YACs can occur regardless of the effect of the DSBs on G2 arrest and cell lethality. If similar events occur in mammalian cells, persistent DSBs could be the initiating events that lead to a loss of heterozygosity and the expression of recessive oncogenes seen in malignant cells.
Detection of tooth fractures in CBCT images using attention index estimation (2014)

The attention index (𝜑) is a number from zero to one that indicates a possible fracture is detected inside a selected tooth. The higher the 𝜑 number, the greater the likelihood for needed attention in the visual examination. The method developed for the 𝜑 estimation extracts a connected component with image properties that are similar to those of a typical tooth fracture. That is, in cone-beam computed tomography (CBCT) images, a fracture appears as a dark canyon inside the tooth. In order to start the visual examination process, the method provides a plane across the geometric center of the suspicious fracture component, which maximizes the number of pixels from that component inside the plane. During visual examination, the user (doctor) can change plane orientations and locations, by manipulating the mouse toward different graphical elements that represent the plane on a 3-D rendition of the tooth, while the corresponding image of the plane is shown at its side. The visual examination aims at confirming or disproving the fracture-detection event. We have designed and implemented these algorithms using the image-foresting transform methodology.
Background Suppression and Agent Detection in Multi-Dimensional Spaces (2006)

We describe a new method for background suppression and agent detection in principal component spaces derived from spectroscopic data to develop an improved trigger sensor for bio-aerosol detection. Simulation results and laboratory data are shown
New options and insights for survivable transport networks (2002)

This article is devoted to a selection of recent topics in survivable networking. New ideas in capacity design and ring-to-mesh evolution are given, as well as a systematic comparison of the capacity requirements of several mesh-based schemes showing how they perform over a range of network graph connectivity. The work provides new options and insights to address the following questions. How does one evolve from an existing ring-based network to a future mesh network? If the facilities graph is very sparse, how can mesh efficiency be much better than rings? How do the options for mesh protection or restoration rank in capacity requirements? How much is efficiency increased if we enrich our network connectivity? We also outline p-cycles, showing this new concept can realize ring-like speed with meshlike efficiency. The scope is limited to conveying basic ideas with an understanding that they could be further adapted for use in IP or DWDM layers with GMPLS-type protocols or a centralized control plane.
Histone demethylase LSD1 deficiency during high-salt diet is associated with enhanced vascular contraction, altered NO-cGMP relaxation pathway, and hypertension (2011)

Histone methylation, a determinant of chromatin structure and gene transcription, was thought to be irreversible, but recent evidence suggests that lysine-specific demethylase-1 (LSD1, Kdm1a) induces demethylation of histone H3 lysine 4 (H3K4) or H3K9 and thereby alters gene transcription. We previously demonstrated a human LSD1 phenotype associated with salt-sensitive hypertension. To test the hypothesis that LSD1 plays a role in the regulation of blood pressure (BP) via vascular mechanisms and gene transcription, we measured BP and examined vascular function and endothelial nitric oxide (NO) synthase (eNOS) expression in thoracic aorta of male wild-type (WT) and heterozygous LSD1 knockout mice (LSD1(+/-)) fed either a liberal salt (HS; 4% NaCl) or restricted salt diet (LS; 0.08% NaCl). BP was higher in LSD1(+/-) than WT mice on the HS diet but not different between LSD1(+/-) and WT mice on the LS diet. Further examination of the mechanisms of this salt-sensitive hypertension in LSD1(+/-) mice on the HS diet demonstrated that plasma renin activity and plasma levels and urinary excretion of aldosterone were less in LSD1(+/-) than WT, suggesting suppressed renin-angiotensin-aldosterone system. In contrast, phenylephrine (Phe)-induced aortic contraction was greater in LSD1(+/-) than WT mice on the HS diet. Treatment of aortic rings with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; a blocker of guanylate cyclase) enhanced Phe contraction in LSD1(+/-) compared with WT mice on the HS diet. Acetylcholine (Ach)-induced relaxation was less in LSD1(+/-) than WT mice on the HS diet. Endothelium removal or pretreatment with N(ω)-nitro-L-arginine methyl ester (blocker of NOS) or ODQ abolished Ach-induced relaxation in aorta of WT but had minimal effect in LSD1(+/-). Vascular relaxation to sodium nitroprusside, an exogenous NO donor and guanylate cyclase activator, was decreased in LSD1(+/-) vs. WT mice on the HS diet. RT-PCR and Western blots revealed decreased eNOS mRNA expression and eNOS and guanylate cyclase protein in the heart and aorta of LSD1(+/-) compared with WT mice on HS diet. Thus, during the HS diet, LSD1 deficiency is associated with hypertension, enhanced vascular contraction, and reduced relaxation via NO-cGMP pathway. The data support a role for LSD1-mediated histone demethylation in the regulation of NOS/guanylate cyclase gene expression, vascular function, and BP during the HS diet.
Loss of Function of a Proline-Containing Protein Confers Durable Disease Resistance in Rice (2009)

Blast disease is a devastating fungal disease of rice, one of the world's staple foods. Race-specific resistance to blast disease has usually not been durable. Here, we report the cloning of a previously unknown type of gene that confers non-race-specific resistance and its successful use in breeding. Pi21 encodes a proline-rich protein that includes a putative heavy metal-binding domain and putative protein-protein interaction motifs. Wild-type Pi21 appears to slow the plant's defense responses, which may support optimization of defense mechanisms. Deletions in its proline-rich motif inhibit this slowing. Pi21 is separable from a closely linked gene conferring poor flavor. The resistant pi21 allele, which is found in some strains of japonica rice, could improve blast resistance of rice worldwide.