gebhart/patrepeval huggingface dataset:
Biomonitoring of arylamines and nitroarenes (2002)

Arylamines and nitroarenes are very important intermediates in the industrial manufacture of dyes, pesticides and plastics, and are significant environmental pollutants. The metabolic steps of N-oxidation and nitroreduction to yield N-hydroxyarylamines are crucial for the toxic properties of arylamines and nitroarenes. Nitroarenes are reduced by microorganisms in the gut or by nitroreductases and aldehyde dehydrogenase in hepatocytes to nitrosoarenes and N-hydroxyarylamines. N-Hydroxyarylamines can be further metabolized to N-sulphonyloxyarylamines, N-acetoxyarylamines or N-hydroxyarylamine N-glucuronide. These highly reactive intermediates are responsible for the genotoxic and cytotoxic effects of this class of compounds. N-Hydroxyarylamines can form adducts with DNA, tissue proteins, and the blood proteins albumin and haemoglobin in a dose-dependent manner. DNA and protein adducts have been used to biomonitor humans exposed to such compounds. All these steps are dependent on enzymes, which are present in polymorphic forms. This article reviews the metabolism of arylamines and nitroarenes and the biomonitoring studies performed in animals and humans exposed to these substances.
Long‐term nonpassaged EGF‐responsive neural precursor cells are stem cells (1998)

We have screened lines of nonpassaged epidermal growth factor-responsive neurospheres from embryonic striatum and brainstem. They have been maintained in defined medium with epidermal growth factor over a period of 2 years and remained in an undifferentiated state to this date. Since isolation from the brain 2 years ago, these nonpassaged epidermal growth factor responsive neurospheres have shown active proliferation and self-renewal capacity. When subplated on a poly-D-lysine coated surface, they resumed differentiation within 24 hours. The differentiation process of the nonpassaged epidermal growth factor responsive neurosphere appeared to recapitulate the neural development in the brain. Many cells migrated, extending radial processes while expressing nestin and S100 in the early 7-day subplating culture. They continued to differentiate into major neural types in 14-day subplating culture, including fibrous and cytoplasmic astrocytes, oligodendrocytes, and serotonin, gamma-aminobutyric acid, and a small number of tyrosine hydroxylase-positive neurons. The nonpassaged epidermal growth factor-responsive neurospheres in many ways resemble hemopoietic cells. Both are proliferative, possess the potential of indefinite self-renewal, yet multipotent, and are capable of resuming the differential pathway. The nonpassaged epidermal growth factor responsive neurospheres meet the criteria of stem cells and have been found to be a useful model to study the development in vitro.
Estimated Prevalence of Age-Associated Memory Impairment Derived From Standardized Tests of Memory Function (1994)

Recent research on the prevalence of age-associated memory impairment (AAMI) has reflected considerable variability, with estimates ranging from 35% to 98%. This variability is attributed to (a) failure to employ the complete diagnostic criteria for AAMI and (b) failure to consider age as a variable in estimating prevalence. Analysis of published normative data on both standard clinical memory tests and computer-simulated everyday memory tests shows a clear increase in the percentage of persons meeting the AAMI memory performance criterion as a function of age. These data are offered as an upper-bound estimate of the prevalence of AAMI, by age decade.
Synthesis of Gallic Acid and Pyrogallol from Glucose:  Replacing Natural Product Isolation with Microbial Catalysis (2000)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTSynthesis of Gallic Acid and Pyrogallol from Glucose: Replacing Natural Product Isolation with Microbial CatalysisSpiros Kambourakis, K. M. Draths, and J. W. FrostView Author Information Departments of Chemistry and Chemical Engineering Michigan State University, East Lansing, Michigan 48824 Cite this: J. Am. Chem. Soc. 2000, 122, 37, 9042–9043Publication Date (Web):September 1, 2000Publication History Received9 March 2000Published online1 September 2000Published inissue 1 September 2000https://pubs.acs.org/doi/10.1021/ja000853rhttps://doi.org/10.1021/ja000853rrapid-communicationACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views2577Altmetric-Citations83LEARN 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 SUBJECTS:Aromatic compounds,Carbohydrates,Gallic acid,Organic reactions,Peptides and proteins Get e-Alerts
A general approach to the analysis of errors and failure modes in the base-calling function in automated fluorescent DNA sequencing (2002)

We describe the analysis of errors and failure modes in the base-calling function in automated DNA sequencing, on instruments in which fluorescently-labeled Sanger dideoxy-sequencing ladders are detected via their times of migration past a fixed detector. A general approach entails the joint use of: (i) well-defined control samples such as M13mp18, and (ii) mathematical simulation of sequencing electropherograms, with the deliberate introduction of different types of distortion and noise. An algorithm, the electrophoretic trace simulator (ETS), is used to calculate electrophoresis traces corresponding to the output data stream of an automated fluorescent DNA sequencer. The ETS accepts a user-defined sequence of nucleotide bases (A, C, G, T) as input, and employs user-adjustable functions to compute the following critical parameters of an electropherogram: peak intensity, peak spacing, peak shape as a function of base number; background, noise, and spectral cross-talk correction (for a sequencer using multiple dyes). We use a combination of M13mp18 controls and simulated electropherograms to analyze two problems of considerable practical importance: (i) variation in electrophoretic migration rates between different lanes of a gel, and (ii) variation in signal intensity due to user-dependent loading artifacts. The issue of base-calling errors and failure modes, for electropherograms that contain noise and distortion, is addressed.
Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs (2016)

Circular RNAs (circRNAs) represent a class of widespread and diverse endogenous RNAs that may regulate gene expression in eukaryotes. However, the regulation and function of human circRNAs remain largely unknown. Here we generate ribosomal-depleted RNA sequencing data from six normal tissues and seven cancers, and detect at least 27,000 circRNA candidates. Many of these circRNAs are differently expressed between the normal and cancerous tissues. We further characterize one abundant circRNA derived from Exon2 of the HIPK3 gene, termed circHIPK3. The silencing of circHIPK3 but not HIPK3 mRNA significantly inhibits human cell growth. Via a luciferase screening assay, circHIPK3 is observed to sponge to 9 miRNAs with 18 potential binding sites. Specifically, we show that circHIPK3 directly binds to miR-124 and inhibits miR-124 activity. Our results provide evidence that circular RNA produced from precursor mRNA may have a regulatory role in human cells.
SINCGARS Internet controller-heart of the digitized battlefield (2002)

The SINCGARS Internet controller (INC) is a packet data capability that is being added to the production deliveries of the SINCGARS System Improvement Program (SIP) radio assemblies. From the prototypes developed in 1993, the INC has evolved to a highly functional router/gateway for the tactical Internet, becoming the heart of the digitized battlefield. Using the SINCGARS Combat Net Radio to support data communications in a mixed voice and data environment was made possible by advances in the SINCGARS radio to improve data reliability and channel access control. Extending the basic data capabilities through distributed switching functionality creates a richly connected packet data network for the entire tactical battlefield.
Cloning and disruption of a putative NaH-antiporter gene of Enterococcus hirae. (1992)

When growing in a sodium-rich environment, wild-type Enterococcus hirae extrudes sodium by two mechanisms, ATP-driven sodium extrusion, and NaH-antiport. Mutant 7683 is unable to grow on sodium-rich media. This is due to two mutations, one inactivating ATP-driven sodium transport and a second rendering NaH-antiport inoperative. 7683 was transformed by electroporation with a gene bank, derived from E. hirae, in an Escherichia coli-E. hirae shuttle vector. Transformants which had regained the ability to grow on sodium-rich media were selected for and the transforming plasmids analyzed. A gene able to restore NaH-antiport activity in 7683 was identified. This gene was named napA. It codes for an extremely hydrophobic protein of 383 amino acids. Hydropathy analysis of this protein indicates that it probably forms 12 transmembraneous helices. In a mutant, possessing only the NaH-antiporter, the napA gene was disrupted by homologous recombination. The resultant strain failed to grow in sodium-rich media, and vesicles isolated from these cells exhibited a defect in sodium proton antiport activity. We conclude that the napA gene codes for a NaH-antiporter. The NapA protein does not exhibit significant homology to any protein in the EMBL genetic data bank.
Taking the Cell by Stealth or Storm? Protein Transduction Domains (PTDs) as Versatile Vectors for Delivery (2002)

A cell delivery system is increasing in use in many areas of cell and molecular biology and bio-medicine. This system is based on a number of naturally occurring protein motifs and/or sequences which show the remarkable ability to rapidly cross the mammalian cell membrane without compromising its structure or function. These so-called Protein Transduction Domains (PTDs) offer unprecedented advantages for intracellular delivery. These advantages include, but are not limited to, their applicability to all cell types (no cell type has yet been described which is not transduced by these PTDs), and the range of cargoes that can be transduced (including peptides, small proteins, full-length enzymes, DNA oligomers, peptide-nucleic acid oligomers, liposomes, and magnetic nanoparticles). Furthermore, the PTDs have been demonstrated to be suitable for in vivo delivery including delivery across the blood brain barrier, and have been shown to cross the plasma membrane rapidly and enter the cytoplasm and nuclear regions of the cell. In this review, the general properties of the most commonly used PTDs are described. The strategies currently being undertaken also highlight that improvements in membrane transduction are possible despite our lack of understanding of the exact biochemical and/or physical mechanisms of transduction. Recent examples of the range of potential applications are also discussed.
Using induced pluripotent stem cells derived neurons to model brain diseases (2017)

The ability to use induced pluripotent stem cells (iPSC) to model brain diseases is a powerful tool for unraveling mechanistic alterations in these disorders. Rodent models of brain diseases have spurred understanding of pathology but the concern arises that they may not recapitulate the full spectrum of neuron disruptions associated with human neuropathology. iPSC derived neurons, or other neural cell types, provide the ability to access pathology in cells derived directly from a patient's blood sample or skin biopsy where availability of brain tissue is limiting. Thus, utilization of iPSC to study brain diseases provides an unlimited resource for disease modelling but may also be used for drug screening for effective therapies and may potentially be used to regenerate aged or damaged cells in the future. Many brain diseases across the spectrum of neurodevelopment, neurodegenerative and neuropsychiatric are being approached by iPSC models. The goal of an iPSC based disease model is to identify a cellular phenotype that discriminates the disease-bearing cells from the control cells. In this mini-review, the importance of iPSC cell models validated for pluripotency, germline competency and function assessments is discussed. Selected examples for the variety of brain diseases that are being approached by iPSC technology to discover or establish the molecular basis of the neuropathology are discussed.
New Steroidal Constituents from the Bulbs of Lilium candidum. (1998)

Eight spirostanol saponins, including four new compounds, and two known furostanol saponins were isolated from the fresh bulbs of Lilium candidum. The structures of new compounds were determined to be (25R,26R)-26-methoxyspirost-5-ene-3 beta,17 alpha-diol 3-O-¿O-alpha-L-rhamnopyranosyl-(1-->2)-O-[beta-D-glucopyranosyl-(1-->4)] -beta-D-glucopyranoside¿, (25R,26R)-26-methoxyspirost-5-ene-3 beta,17 alpha-diol 3-O-¿O-alpha-L-rhamnopyranosyl-(1-->2)-O-[6-O-acetyl-beta-D-glucopyranos yl- (1-->4)]-beta-D-glucopyranoside¿, (25R,26R)-26-methoxyspirost-5-ene-3 beta,17 alpha-diol 3-O-¿O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside¿ and (25S)-spirost-5-ene-3 beta,27-diol 3-O-¿O-beta-D-glucopyranosyl-(1-->3)-O-alpha-L-rhamnopyranosyl-(1-->2)-O - [beta-D-glucopyranosyl-(1-->4)]-beta-D-glucopyranoside¿, respectively, on the basis of spectroscopic analysis, including two-dimensional NMR techniques, and the result of hydrolysis. The inhibitory activity of the isolated saponins on Na+/K+ ATPase was evaluated.
Structural Stabilities of the Trimethylsilylmethyl and Neopentyl Groups in the Preparation of Phosphonyl Dichlorides (1966)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructural Stabilities of the Trimethylsilylmethyl and Neopentyl Groups in the Preparation of Phosphonyl DichloridesR. J. HartleCite this: J. Org. Chem. 1966, 31, 12, 4288–4290Publication Date (Print):December 1, 1966Publication History Published online1 May 2002Published inissue 1 December 1966https://pubs.acs.org/doi/10.1021/jo01350a536https://doi.org/10.1021/jo01350a536research-articleACS PublicationsRequest reuse permissionsArticle Views93Altmetric-Citations8LEARN 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-Alertsclose Get e-Alerts
Reduced Caudate and Nucleus Accumbens Response to Rewards in Unmedicated Individuals With Major Depressive Disorder (2009)

These results suggest that basal ganglia dysfunction in major depression may affect the consummatory phase of reward processing. Additionally, morphometric results suggest that anhedonia in major depression is related to caudate volume.
A chemical genetic roadmap to improved tomato flavor (2017)

Modern commercial tomato varieties are substantially less flavorful than heirloom varieties. To understand and ultimately correct this deficiency, we quantified flavor-associated chemicals in 398 modern, heirloom, and wild accessions. A subset of these accessions was evaluated in consumer panels, identifying the chemicals that made the most important contributions to flavor and consumer liking. We found that modern commercial varieties contain significantly lower amounts of many of these important flavor chemicals than older varieties. Whole-genome sequencing and a genome-wide association study permitted identification of genetic loci that affect most of the target flavor chemicals, including sugars, acids, and volatiles. Together, these results provide an understanding of the flavor deficiencies in modern commercial varieties and the information necessary for the recovery of good flavor through molecular breeding.
Norepinephrine and Serotonin Transporter Genes: Impact on Treatment Response in Depression (2010)

The present findings do not support a major impact of the NET and 5-HTT genes on antidepressant treatment response in major depression per se. However, there might be an impact of a -/CT ins/del polymorphism in the enhancer domain of the NET gene on treatment response in melancholic depression, which remains to be functionally investigated in future studies. The observed significant influence of the 5-HTT gene variation on antidepressant treatment in anxious depression points to anxious depression as a potential diagnostic entity of its own, requiring specific diagnostic and therapeutic attention.
Interleukin-12 inhibits hepatitis B virus replication in transgenic mice (1997)

Interleukin-12 (IL-12) is a heterodimeric cytokine produced by antigen-presenting cells that has the ability to induce gamma interferon (IFN-gamma) secretion by T and natural killer cells and to generate normal Th1 responses. These properties suggest that IL-12 may play an important role in the immune response to many viruses, including hepatitis B virus (HBV). Recently, we have shown that HBV-specific cytotoxic T lymphocytes inhibit HBV replication in the livers of transgenic mice by a noncytolytic process that is mediated in part by IFN-gamma. In the current study, we demonstrated that the same antiviral response can be initiated by recombinant murine IL-12 and we showed that the antiviral effect of IL-12 extends to extrahepatic sites such as the kidney. Southern blot analyses revealed the complete disappearance of HBV replicative intermediates from liver and kidney tissues at IL-12 doses that induce little or no inflammation in these tissues. In addition, immunohistochemical analysis demonstrated the disappearance of cytoplasmic hepatitis B core antigen from both tissues after IL-12 treatment, suggesting that IL-12 either prevents the assembly or triggers the degradation of the nucleocapsid particles within which HBV replication occurs. Importantly, we demonstrated that although IFN-gamma, tumor necrosis factor alpha, and IFN-alpha/beta mRNA are induced in the liver and kidney after IL-12 administration, the antiviral effect of IL-12 is mediated principally by its ability to induce IFN-gamma production in this model. These results suggest that IL-12, through its ability to induce IFN-gamma, probably plays an important role in the antiviral immune response to HBV during natural infection. Further, since relatively nontoxic doses of recombinant IL-12 profoundly inhibit HBV replication in the liver and extrahepatic sites in this model, IL-12 may have therapeutic value as an antiviral agent for the treatment of chronic HBV infection.
Direct Plasma Sample Injection in Multiple-Component LC−MS−MS Assays for High-Throughput Pharmacokinetic Screening (1999)

The simultaneous dosing of numerous compounds followed by multiple-component analysis using LC−MS−MS (the N-in-1 approach) has significantly improved the throughput of the drug-screening process. However, plasma samples still need to be extracted before LC−MS−MS analysis, which frequently limits the throughput of the assay. In this work, a high-throughput on-line extraction technique has been developed for multiple-component LC−MS−MS assays using a high-flow column-switching technique. In N-in-1 LC−MS−MS assays, high sensitivity is required since the dose level is generally reduced to minimize drug−drug interactions. In addition, good chromatographic separation is essential to minimize interference and suppression effects. The direct plasma sample injection method developed in this work has successfully met the two requirements for multiple-component LC−MS−MS assays in high-throughput pharmacokinetic screening. Plasma samples containing a large number of potential drug candidates were directly injected onto an extraction column operated under a flow rate sufficiently high to exhibit a turbulent-flow profile. The extracted analytes were then eluted onto an analytical column via column switching for LC−MS−MS analysis. The use of turbulent flow resulted in a faster and more rugged extraction with reduced carryover compared with results obtained under laminar-flow conditions. Meanwhile, the use of a column-switching method maintained the chromatographic resolving power and high sensitivity of the LC−MS−MS assay. Separation efficiency, dynamic range, accuracy, and precision comparable with those of solid-phase extraction have been achieved with the turbulent-flow column-switching technique. As a result, this technique has been successfully and routinely used for high-throughput pharmacokinetic screening.
FKBP12-Rapamycin-associated Protein or Mammalian Target of Rapamycin (FRAP/mTOR) Localization in the Endoplasmic Reticulum and the Golgi Apparatus (2003)

FKBP12-rapamycin-associated protein (FRAP) or mammalian target of rapamycin (mTOR) and its effector proteins form a critical signaling pathway that regulates eukaryotic cell growth and proliferation. Although the protein components in this pathway have begun to be identified, little is known about their subcellular localization or the physiological significance of their localization. By immunofluorescence, we find that both endogenous and recombinant FRAP/mTOR proteins show localization predominantly in the endoplasmic reticulum (ER) and the Golgi apparatus. Consistent with this finding, FRAP/mTOR is cofractionated with calnexin, an ER marker protein. Biochemical characterization suggests that FRAP/mTOR is a peripheral ER/Golgi protein with tight membrane association. Finally, we have identified domains of FRAP/mTOR which may mediate its association with the ER and the Golgi apparatus.
Treatment of interstitial cystitis with intravesical heparin (1994)

In over half of the patients studied, intravesical heparin controls the symptoms of interstitial cystitis with continued improvement even after one year of therapy.