gebhart/patrepeval huggingface dataset:
Investigating the in vitro metabolism of fipexide: characterization of reactive metabolites using liquid chromatography/mass spectrometry (2007)

The in vitro metabolism of the nootropic drug fipexide was studied using different liquid chromatography/mass spectrometry (LC/MS) techniques. This drug has been withdrawn from the market due to toxic effects. No previous reports have investigated the possible involvement of reactive metabolites in the toxicity of fipexide. The hydrolysis of this drug leads to the formation of two potentially toxic species, 3,4-methylenedioxybenzylpiperazine (MDBP) and 4-chlorophenoxyacetic acid (4-CPA). Here, we investigate the in vitro metabolism of fipexide in human, rat, mouse and dog, as well as of MDBP and 4-CPA in human and rat, while focusing on the formation of reactive metabolites. A combination of LC/MS analyses on a hybrid quadrupole-linear ion trap instrument and accurate mass data from QqTOF measurements was employed for the characterization of these metabolites. Microsomal metabolites of fipexide were MDBP, 4-CPA, fipexide N-oxide or hydroxyl, demethylenated fipexide and other minor ones, all of which were investigated by tandem mass spectrometry. Reactive metabolites were detected using several trapping procedures with small molecules such as glutathione, its ethyl ester derivative and N-acetylcysteine. The demethylenated metabolite, a catechol, formed its corresponding ortho-quinone, which readily reacts with these nucleophiles. MDBP was studied in a similar manner, due to its ability to form an analogous catechol. Because of its acidic nature, 4-CPA was assessed for possible acylglucuronide and acyl-CoA thioester metabolites, which could also be involved in bioactivation pathways. Several important metabolites were identified as potential mediators of toxicity via protein binding.
Extended Gaussian images (1984)

This is a primer on extended Gaussian images. Extended Gaussian images are useful for representing the shapes of surfaces. They can be computed easily from: 1. needle maps obtained using photometric stereo; or 2. depth maps generated by ranging devices or binocular stereo. Importantly, they can also be determined simply from geometric models of the objects. Extended Gaussian images can be of use in at least two of the tasks facing a machine vision system: 1. recognition, and 2. determining the attitude in space of an object. Here, the extended Gaussian image is defined and some of its properties discussed. An elaboration for nonconvex objects is presented and several examples are shown.
Microbial transformation of A23187, a divalent cation ionophore antibiotic (1979)

A23187 is an ionophore antibiotic that forms dimeric complexes with divalent cations such an Mn2+ and Ca2+. Over 200 randomly selected soil microorganisms were incubated with A23187. None of these cultures was capable of transforming this compound. In contrast, many microorganisms were able to modify the methyl ester of A23187. The transformation products produced by one culture, Streptomyces chartreusis, were isolated and identified as 16-hydroxy-N-demethyl A23187 methyl ester, 16-hydroxy-A23187 methyl ester, and N-demethyl A23187 methyl ester. These ester derivatives lack most of the ionophore properties of the acids and cannot readily form dimeric complexes with divalent cations. However, they could be hydrolyzed by a mild treatment with ethanolic KOH to free acids that possess good ionophore activity. The use of the ester substrate in conjunction with the hydrolysis procedure is, at the present time, the only known method for microbiologically producing A23187 derivatives.
Pharmacokinetic and Pharmacodynamic Properties of Anti-VEGF Drugs After Intravitreal Injection (2015)

Subretinal neovascularization and pathologic ocular angiogenesis are common causes of progressive, irreversible impairment of central vision, and dramatically affect quality of life. Anti-vascular endothelial growth factor (anti-VEGF) therapy has improved the quality of life for many patients with age-related macular degeneration, diabetic retinopathy, and other ocular diseases involving neovascularization and edema. In these pathologies, the inhibition of intraocular VEGF is the only therapy that can preserve vision. Four anti-VEGF drugs are currently used to treat ocular neovascularization; pegaptanib, ranibizumab, and aflibercept have been approved for this condition, while bevacizumab can be used off-label. Anti-VEGF therapy is administered regularly for many months or years because its suspension or discontinuation may cause recurrence of neovascularization. On the other hand, VEGF is necessary for the survival of retinal and choroidal endothelial cells. Experimental studies in animal models have shown that local inhibition of VEGF causes thinning and atrophy of the choriocapillaris and degeneration of photoreceptors, primarily cones. These studies combined with clinical experience indicated that prolonged VEGF inhibition could impair retinal function. Moreover, anti-VEGF compounds can cross the blood-retina barrier, enter the systemic circulation, and inhibit serum VEGF. Since circulating VEGF protects blood vessel integrity, prolonged anti-VEGF treatment could induce thromboembolic adverse events from vascular causes such as heart attack and stroke, and even death. The ocular dosing regimen and systemic toxicity of anti-VEGF compounds are therefore central concerns. A better understanding of this topic requires knowledge of the metabolism, tissue distribution, and clearance of anti-VEGF compounds. This manuscript reviews the properties of anti-VEGF compounds following intravitreal administration.
Histological and biological evolution of human premalignant breast disease. (2001)

Most human invasive breast cancers (IBCs) appear to develop over long periods of time from certain pre-existing benign lesions. Of the many types of benign lesions in the human breast, only a few appear to have significant premalignant potential. The best characterized of these include atypical hyperplasias and in situ carcinomas and both categories are probably well on along the evolutionary pathway to IBC. Very little is known about earlier premalignant alterations. All types of premalignant breast lesions are relatively common but only a small proportion appear to progress to IBC. They are currently defined by their histological features and their prognosis is imprecisely estimated from indirect epidemiological evidence. Although lesions within specific categories look alike, they must possess underlying biological differences causing some to remain stable and others to progress. Recent studies suggest that they evolve by highly diverse genetic mechanisms and research into these altered pathways may identify specific early defects that can be targeted to prevent premalignant lesions from developing or becoming cancerous. It is far more rational to think that breast cancer can be prevented than cured once it has developed fully. This review discusses histological models of human premalignant breast disease that provide the framework for scientific investigations into the biological alterations behind them and examples of specific biological alterations that appear to be particularly important.
Suppression of Cellular Immune Response in Spodoptera litura (Lepidoptera: Noctuidae) Larvae by Endophytic Fungi Nigrospora oryzae and Cladosporium uredinicola (2014)

Abstract Endophytic fungi are a group of microbial plant symbionts that occur in living tissues of plants without causing visible disease symptoms. The mechanism underlying the anti-insect properties of endophytes is mainly attributed to the production of various alkaloid-based defensive compounds. The current study reveals the cytotoxic effects of endophytic Nigrospora oryzae- and Cladosporium uredinicola-infected cauliflower plants on larval hemocytes of Spodoptera litura (F.). Larvae fed on leaves of endophyte-infected plants exhibited abnormalities such as change in shape, extensive vacuolization, and necrosis in significantly higher percentage of hemocytes. The percentage of abnormal hemocytes increased with increase in feeding duration. The cytotoxic effect of endophytic fungi on the hemocytes ultimately leads to adverse effects on survival and fitness of the insect.
Molecular Dynamics Simulation of Hexamine and Suberic Acid (2003)

In order to perform a molecular dynamics (MD) simulation of the incommensurate crystalline structure hexamethylenetetramine suberate (C 6 H 12 N 4 )(HOOC-(CH 2 ) 6 -COOH), we present in a first step the separate simulations of the crystalline structure of each of the two pure components, hexamethylenetetramine (HMT) and suberic acid. The domain decomposition parallel MD program ddgmq is used for this purpose. A second-generation consistent force field (CFF91) is employed to describe the interactions between atoms. Starting from experimental crystal structures, both pure components were heated from low to high temperatures. Our MD results show that the HMT system can be well represented by CFF91. In the case of suberic acid the layered structure of the crystal is largely preserved although deviations in the unit cell lengths from the experimental values are ∼10%. Rather than attempt a complex re-parametrisation of CFF91 we chose to impose a fixed compensating external pressure tensor to correct for the deficiencies of the chosen force field. After optimising this compensating external pressure tensor at one temperature we find that experimental lattice constants and angles can be well reproduced over a range of temperatures.
Enzymatic synthesis ofbiotin-labeled polynucleotides: Novel nucleic acidaffinity probes (1981)

ABSTRACT AnalogsofdUTPandUTPthat contain a biotinmolecule covalently bound to the C-5position ofthe pyrimidinering through an allylamine linker arm have been synthesized.Thesebiotin-labeled nucleotides areefficientsubstrates forava-rietyofDNAandRNA polynerases invitro. Polynucleotides con-taininglowlevelsofbiotinsubstitution (50'moleculesorfewerperkilobase) have denaturation, reassociation, and hybridizationcharacteristics similar. to those ofunsubstituted controls. Biotin-labeledpolynucleotides, bothsingle anddoublestranded, arese-lectively and quantitatively retained on avidin-Sepharose, evenafterextensivewashingwith8Murea, 6Mguanidinehydrochlo-ride, or 99%formamide. In addition, biotin-labeled polynucleo- tides can be selectively immunoprecipitated in the presence ofantibiotin antibody and Staphylococcus aureus protein A. Theuniquefeaturesofbiotin-labeledpolynucleotidessuggestthattheywillbeusefulaffinityprobesforthedetectionandisolationofspe-cific DNAandRNAsequences. Nucleotideanalogsthat
New Equations to Estimate GFR in Children with CKD (2009)

The Schwartz formula was devised in the mid-1970s to estimate GFR in children. Recent data suggest that this formula currently overestimates GFR as measured by plasma disappearance of iohexol, likely a result of a change in methods used to measure creatinine. Here, we developed equations to estimate GFR using data from the baseline visits of 349 children (aged 1 to 16 yr) in the Chronic Kidney Disease in Children (CKiD) cohort. Median iohexol-GFR (iGFR) was 41.3 ml/min per 1.73 m(2) (interquartile range 32.0 to 51.7), and median serum creatinine was 1.3 mg/dl. We performed linear regression analyses assessing precision, goodness of fit, and accuracy to develop improvements in the GFR estimating formula, which was based on height, serum creatinine, cystatin C, blood urea nitrogen, and gender. The best equation was: GFR(ml/min per 1.73 m(2))=39.1[height (m)/Scr (mg/dl)](0.516) x [1.8/cystatin C (mg/L)](0.294)[30/BUN (mg/dl)](0.169)[1.099](male)[height (m)/1.4](0.188). This formula yielded 87.7% of estimated GFR within 30% of the iGFR, and 45.6% within 10%. In a test set of 168 CKiD patients at 1 yr of follow-up, this formula compared favorably with previously published estimating equations for children. Furthermore, with height measured in cm, a bedside calculation of 0.413*(height/serum creatinine), provides a good approximation to the estimated GFR formula. Additional studies of children with higher GFR are needed to validate these formulas for use in screening all children for CKD.
MICROALGAE AS A SOURCE OF FATTY ACIDS (1996)

ABSTRACT Microalgae are a very diverse group of organisms that consist of both prokaryotic and eukaryotic forms. Although most microalgae are phototrophic, some species are also capable of heterotrophic growth. Some species of microalgae can be induced to overproduce particular fatty acids through simple manipulations of the physical and chemical properties of the culture medium. As a result of the profound differences in cellular organization and growth modes and the ability to manipulate their fatty acid content, microalgae represent a significant source of unusual and valuable lipids and fatty acids. The utilization of microalgal lipids and fatty acids as food components requires that these organisms be grown at large scale under controlled conditions. Several growth systems have been developed for large scale growth of phototrophic microalgae using either natural sunlight or artificial light, but their lack of control of culturing parameters or their high cost of operation have limited their utility for the production of food products. Instead, large scale cultivation of heterotrophic microalgae using classical fermentation systems provides consistent biomass produced under highly controlled conditions at low cost. Microalgae contain many of the major lipid classes and fatty acids found in other organisms. However, they are also the principal producers in the biosphere of some polyunsaturated fatty acids, especially docosahexaenoic acid (DHA). The high DHA content found in some algae is currently being utilized to supplement infant formula to enable it to more closely resemble human breast milk. Thus, the commercialization of DHA from microalgae demonstrates the value of these organisms as a source of useful fatty acids.
Learning Automation Policies for Pervasive Computing Environments (2005)

If current trends in cellular phone technology, personal digital assistants, and wireless networking are indicative of the future, we can expect our environments to contain an abundance of networked computational devices and resources. We envision these devices acting in an orchestrated manner to meet users' needs, pushing the level of interaction away from particular devices and towards interactions with the environment as a whole. Computation will be based not only on input explicitly provided by the user, but also on contextual information passively collected by networked sensing devices. Configuring the desired responses to different situations will need to be easy for users. However, we anticipate that the triggering situations for many desired automation policies will be complex, unforeseen functions of low-level contextual information. This is problematic since users, though easily able to perceive triggering situations, will not be able to define them as functions of the devices' available contextual information, even when such a function (or a close approximation) does exist. In this paper, we present an alternative approach for specifying the automation rules of a pervasive computing environment using machine learning techniques. Using this approach, users generate training data for an automation policy through demonstration, and, after training is completed, a learned function is employed for future automation. This approach enables users to automate the environment based on changes in the environment that are complex, unforeseen combinations of contextual information. We developed our learning service within Gaia, our pervasive computing system, and deployed it within our prototype pervasive computing environment. Using the system, we were able to have users demonstrate how sound and lighting controls should adjust to different applications used within the environment, the users present, and the locations of those users and then automate those demonstrated preferences
Streamlined analysis of duplex sequencing data with Du Novo (2016)

Duplex sequencing was originally developed to detect rare nucleotide polymorphisms normally obscured by the noise of high-throughput sequencing. Here we describe a new, streamlined, reference-free approach for the analysis of duplex sequencing data. We show the approach performs well on simulated data and precisely reproduces previously published results and apply it to a newly produced dataset, enabling us to type low-frequency variants in human mitochondrial DNA. Finally, we provide all necessary tools as stand-alone components as well as integrate them into the Galaxy platform. All analyses performed in this manuscript can be repeated exactly as described at http://usegalaxy.org/duplex .
Ultrarapid Engineering of Biomimetic Materials and Tissues: Fabrication of Nano‐ and Microstructures by Plastic Compression (2005)

Abstract Currently, the concept of engineered tissues depends on the ability of cultured cells to fabricate new tissue around a scaffold. This is inherently slow and expensive and has had limited success so far. We report here a new process for the cell‐independent, controlled engineering of biomimetic scaffolds by rapid removal of fluid from hyperhydrated collagen gel (or other) constructs, using plastic compression (PC). PC fabrication produces dense, cellular, mechanically strong native collagen structures with controllable nano‐ and microscale biomimetic structures. The huge‐scale shrinkage (&gt; 100‐fold) provides the ability to introduce controllable mechanical properties, microlayering, and embossed interface topography without cell participation, but with high cell viability. Critically, this takes minutes rather than the conventional days and weeks. The rapidity and biomimetic potential of the PC fabrication process at the mesoscale opens a new route for the production of biomaterials and patient‐customized tissues. It also represents a new concept in ‘engineering’ tissues.
Dominant negative mutation of the TGF-β receptor blocks hypoxia-induced pulmonary vascular remodeling (2005)

The present study utilized a novel transgenic mouse model that expresses an inducible dominant negative mutation of the transforming growth factor (TGF)-beta type II receptor (DnTGFbetaRII mouse) to test the hypothesis that TGF-beta signaling plays an important role in the pathogenesis of chronic hypoxia-induced increases in pulmonary arterial pressure and vascular and alveolar remodeling. Nine- to 10-wk-old male DnTGFbetaRII and control nontransgenic (NTG) mice were exposed to normobaric hypoxia (10% O2) or air for 6 wk. Expression of DnTGFbetaRII was induced by drinking 25 mM ZnSO4 water beginning 1 wk before hypoxic exposure. Hypoxia-induced increases in right ventricular pressure, right ventricular mass, pulmonary arterial remodeling, and muscularization were greatly attenuated in DnTGFbetaRII mice compared with NTG controls. Furthermore, the stimulatory effects of hypoxic exposure on pulmonary arterial and alveolar collagen content, appearance of alpha-smooth muscle actin-positive cells in alveolar parenchyma, and expression of extracellular matrix molecule (including collagen I and III, periostin, and osteopontin) mRNA in whole lung were abrogated in DnTGFbetaRII mice compared with NTG controls. Hypoxic exposure had no effect on systemic arterial pressure or heart rate in either strain. These data support the hypothesis that endogenous TGF-beta plays an important role in pulmonary vascular adaptation to chronic hypoxia and that disruption of TGF-beta signaling attenuates hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, pulmonary arterial hypertrophy and muscularization, alveolar remodeling, and expression of extracellular matrix mRNA in whole lung.
Uncovering of a Short Internal Peptide Activates a tRNA Synthetase Procytokine (2012)

In higher organisms, aminoacyl-tRNA synthetases developed receptor-mediated ex-translational functions that are activated by various natural mechanisms. Hydrogen-deuterium exchange combined with mass spectrometry and small-angle x-ray scattering showed that activation of the cytokine function of the 528-amino acid human tyrosyl-tRNA synthetase was associated with pinpointed uncovering of a miniature internal ELR tripeptide that triggers receptor signaling. The results reveal the structural simplicity of how the ex-translational function is implemented.
A cis -Acting Element That Directs Circular Adeno-Associated Virus Replication and Packaging (2002)

A novel pathway of adeno-associated virus (AAV) replication marked by the assembly of circular monomer duplex intermediates (cAAV) has been recently discovered. In the present report we identify a single AD domain of the inverted terminal repeat as a minimal origin of cAAV replication. A small internal palindrome (BB'), necessary for optimal Rep-inverted terminal repeat interaction, does not contribute to the efficiency of cAAV replication, while the terminal resolution site is an essential cis-acting element. Furthermore, recombinant cAAV vectors that encompass only the AD domain replicate exclusively in a circular form and no detectable linear duplex replicative intermediates are generated, suggesting that both pathways of AAV replication are independent and can be separated. In addition, we show that cAAVs are efficient templates for encapsidation of single-stranded DNA genomes, an observation that assigns a biological role for these novel replication species. Together, these findings shed new light on the current model of AAV replication and packaging.
Effects of Gasoline Composition on Exhaust Emissions and Driveability (1990)

&lt;div class="htmlview paragraph"&gt;A study of the effects of changes in gasoline composition is one area to explore in our effort to reduce tailpipe emissions from vehicles. However, affects on vehicle performances should also be considered from the perspective of practical useage.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;In this paper, the influence of gasoline composition (aromatics),volatility, and MTBE blending on engine outlet and tailpipe emissions are discussed,in particular,forcusing on distillation properties which have a close relationship to driveability.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;Under stable driving conditios and without a catalitic converter, the effects of gasoline volatility is small, while aromatics in gasoline affect exhaust HC and NOx emissions. MTBE has a leaning effect on the engine intake air/fuel mixture.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;During a transient driving cycle, a high gasoline 50% distillation temperature causes poor driveability, as a result, HC emissions increase.&lt;/div&gt;
Thin film resonators and filters (2003)

This paper presents an overview of the thin film resonator technology as it has been developed over the past few years. A brief discussion of the basic elements of wireless systems is described in order to set the stage for a description of the important enabling aspects of what is generally termed the thin film resonator (TFR) technology. Features of TFRs will be described along with specific examples of resonators and filters. The all important packaging problem is described in the context of device performance and manufacturing.
Nascent structures during the polymerization of ethylene. I: Morphology and model of growth (1973)

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