gebhart/patrepeval huggingface dataset:
Sleep networks and the anatomic and physiologic connections with respiratory control (2003)

A central neuronal network regulates airway functions from the nares to the bronchioles and is an integral component of a regulatory system for brain control of breathing and airway patency during wakefulness and sleep. This network, components of which include sleep generating sites and monoaminergic neurons in particular, is characterized by reciprocal interconnections, parallel organization, and state-dependent activity patterns, which can be influenced by both genes and environment. Sleep generating neurons are interconnected with the monoaminergic containing cells to the extent that sleep-related changes in upper and lower airway patency could be due to inhibitory influences of sleep-activated neurons on serotonergic and noradrenergic producing cells. Neurochemical studies and physiologic experiments show that serotonergic and noradrenergic producing cells can make parallel pathways, directly innervating the hypoglossal motor cells regulating upper airway dilating muscles, and vagal preganglionic neurons providing cholinergic outflow to the airways. Activation of serotonergic and noradrenergic cell groups preferentially increases activity of the genioglossus muscle, but diminishes cholinergic outflow to the airways. Hence, inhibition of monoaminergic neurons during sleep may lead to a decrease in upper airway dilating forces and an elevation of cholinergic outflow to the airways. Qualitatively different responses of hypoglossal and airway-related vagal preganglionic neurons (AVPNs) occur in response to endogenously released serotonin or norepinephrine and could be related to its simultaneous action on different serotonin or norepinephrine receptor subtypes. Dysfunction of monaminergic cell groups during sleep may predispose to upper airway occlusion as well as bronchoconstriction. Pharmacological corrections of alterations of these transmitter specific converging systems might be an avenue for treatment of sleep related airway disorders such as sleep apnea and worsening of asthma.
Development of primitive and definitive hematopoiesis from nonhuman primate embryonic stem cells in vitro (2004)

Although information about the development of primitive and definitive hematopoiesis has been elucidated in murine embryos and embryonic stem (ES) cells, there have been few in vitro studies of these processes in primates. In this study, we investigated hematopoietic differentiation from cynomolgus monkey ES cells grown on OP9, a stromal cell line deficient in macrophage colony-stimulating factor. Primitive erythrocytes (EryP) and definitive erythrocytes (EryD) developed sequentially from ES cells in the culture system; this was confirmed by immunostaining and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of embryonic, fetal and adult globin genes. EryP were detected on day 8 without exogenous erythropoietin (EPO), whereas EryD appeared on day 16 and had an indispensable requirement for exogenous EPO. RT-PCR analysis of the cultures revealed a sequential expression of genes associated with primitive and definitive hematopoietic development that was equivalent to that seen during primate ontogeny in vivo. Vascular endothelial growth factor (VEGF) increased, in a dose-dependent manner, not only the number of floating hematopoietic cells, but also the number of adherent hematopoietic cell clusters containing CD34-positive immature progenitors. In colony assays, exogenous VEGF also had a dose-dependent stimulatory effect on the generation of primitive erythroid colonies. More efficient primitive and definitive erythropoiesis was induced by re-plating sorted CD34-positive cells. Thus, this system reproduces early hematopoietic development in vitro and can serve as a model for analyzing the mechanisms of hematopoietic development in primates.
miR-331-3p Regulates ERBB-2 Expression and Androgen Receptor Signaling in Prostate Cancer (2009)

MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression and are aberrantly expressed in human cancer. The ERBB-2 tyrosine kinase receptor is frequently overexpressed in prostate cancer and is associated with disease progression and poor survival. We have identified two specific miR-331-3p target sites within the ERBB-2 mRNA 3'-untranslated region and show that miR-331-3p expression is decreased in prostate cancer tissue relative to normal adjacent prostate tissue. Transfection of multiple prostate cancer cell lines with miR-331-3p reduced ERBB-2 mRNA and protein expression and blocked downstream phosphatidylinositol 3-kinase/AKT signaling. Furthermore, miR-331-3p transfection blocked the androgen receptor signaling pathway in prostate cancer cells, reducing activity of an androgen-stimulated prostate-specific antigen promoter and blocking prostate-specific antigen expression. Our findings provide insight into the regulation of ERBB-2 expression in cancer and suggest that miR-331-3p has the capacity to regulate signaling pathways critical to the development and progression of prostate cancer cells.
Sterols. LXIX. Oxidation Products of Sarsasapogenin. Sarsasapogenoic Acid and Related Substances (1939)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSterols. LXIX. Oxidation Products of Sarsasapogenin. Sarsasapogenoic Acid and Related SubstancesRussell E. Marker and Ewald. RohrmannCite this: J. Am. Chem. Soc. 1939, 61, 8, 2072–2077Publication Date (Print):August 1, 1939Publication History Published online1 May 2002Published inissue 1 August 1939https://doi.org/10.1021/ja01877a032Request reuse permissions Article Views39Altmetric-Citations3LEARN 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 InReddit PDF (566 KB) Get e-Alertsclose Get e-Alerts
Optical phased array technology (1996)

Optical phased arrays represent an enabling new technology that makes possible simple affordable, lightweight, optical sensors offering very precise stabilization, random-access pointing programmable multiple simultaneous beams, a dynamic focus/defocus capability, and moderate to excellent optical power handling capability. These new arrays steer or otherwise operate on an already formed beam. A phase profile is imposed on an optical beam as it is either transmitted through or reflected from the phase shifter array. The imposed phase profile steers, focuses, fans out, or corrects phase aberrations on the beam. The array of optical phase shifters is realized through lithographic patterning of an electrical addressing network on the superstrate of a liquid crystal waveplate. Refractive index changes sufficiently large to realize full-wave differential phase shifts can be effected using low (<10 V) voltages applied to the liquid crystal phase plate electrodes. High efficiency large-angle steering with phased arrays requires phase shifter spacing on the order of a wavelength or less; consequently addressing issues make 1-D optical arrays much more practical than 2-D arrays. Orthogonal oriented 1-D phased arrays are used to deflect a beam in both dimensions. Optical phased arrays with apertures on the order of 4 cm by 4 cm have been fabricated for steering green, red, 1.06 /spl mu/m, and 10.6 /spl mu/m radiation. System concepts that include a passive acquisition sensor as well as a laser radar are presented.
Arsenic atom location on passivated silicon (111) surfaces (1987)

The position of As atoms on a clean Si(111) surface has been determined with x-ray standing waves in ultrahigh vacuum. The As atoms occupy exclusively the top half of the silicon (111) double plane and lie at 0.17 \AA{} above the unrelaxed bulk terminated silicon (111) plane. This value is in good agreement with recent total-energy minimization calculations. A significant but limited stability of As passivated surfaces is observed upon exposure to various ambients. We also present general arguments showing how surface specificity can be achieved with x-ray standing-wave measurements such as the above, where bulk-symmetry site-occupancy rules are broken.
Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease (2018)

Emerging coronaviruses (CoVs) cause severe disease in humans, but no approved therapeutics are available. The CoV nsp14 exoribonuclease (ExoN) has complicated development of antiviral nucleosides due to its proofreading activity. We recently reported that the nucleoside analogue GS-5734 (remdesivir) potently inhibits human and zoonotic CoVs <i>in vitro</i> and in a severe acute respiratory syndrome coronavirus (SARS-CoV) mouse model. However, studies with GS-5734 have not reported resistance associated with GS-5734, nor do we understand the action of GS-5734 in wild-type (WT) proofreading CoVs. Here, we show that GS-5734 inhibits murine hepatitis virus (MHV) with similar 50% effective concentration values (EC<sub>50</sub>) as SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Passage of WT MHV in the presence of the GS-5734 parent nucleoside selected two mutations in the nsp12 polymerase at residues conserved across all CoVs that conferred up to 5.6-fold resistance to GS-5734, as determined by EC<sub>50</sub> The resistant viruses were unable to compete with WT in direct coinfection passage in the absence of GS-5734. Introduction of the MHV resistance mutations into SARS-CoV resulted in the same <i>in vitro</i> resistance phenotype and attenuated SARS-CoV pathogenesis in a mouse model. Finally, we demonstrate that an MHV mutant lacking ExoN proofreading was significantly more sensitive to GS-5734. Combined, the results indicate that GS-5734 interferes with the nsp12 polymerase even in the setting of intact ExoN proofreading activity and that resistance can be overcome with increased, nontoxic concentrations of GS-5734, further supporting the development of GS-5734 as a broad-spectrum therapeutic to protect against contemporary and emerging CoVs.<b>IMPORTANCE</b> Coronaviruses (CoVs) cause severe human infections, but there are no approved antivirals to treat these infections. Development of nucleoside-based therapeutics for CoV infections has been hampered by the presence of a proofreading exoribonuclease. Here, we expand the known efficacy of the nucleotide prodrug remdesivir (GS-5734) to include a group β-2a CoV. Further, GS-5734 potently inhibits CoVs with intact proofreading. Following selection with the GS-5734 parent nucleoside, 2 amino acid substitutions in the nsp12 polymerase at residues that are identical across CoVs provide low-level resistance to GS-5734. The resistance mutations decrease viral fitness of MHV <i>in vitro</i> and attenuate pathogenesis in a SARS-CoV animal model of infection. Together, these studies define the target of GS-5734 activity and demonstrate that resistance is difficult to select, only partial, and impairs fitness and virulence of MHV and SARS-CoV, supporting further development of GS-5734 as a potential effective pan-CoV antiviral.
A human aminoacyl-tRNA synthetase as a regulator of angiogenesis (2002)

Aminoacyl-tRNA synthetases catalyze the first step of protein synthesis. It was shown recently that human tyrosyl-tRNA synthetase (TyrRS) can be split into two fragments having distinct cytokine activities, thereby linking protein synthesis to cytokine signaling pathways. Tryptophanyl-tRNA synthetase (TrpRS) is a close homologue of TyrRS. A natural fragment, herein designated as mini TrpRS, was shown by others to be produced by alternative splicing. Production of this fragment is reported to be stimulated by IFN-gamma, a cytokine that also stimulates production of angiostatic factors. Mini TrpRS is shown here to be angiostatic in a mammalian cell culture system, the chicken embryo, and two independent angiogenesis assays in the mouse. The full-length enzyme is inactive in the same assays. Thus, protein synthesis may be linked to the regulation of angiogenesis by a natural fragment of TrpRS.
Specific Targeting of EGP-2+ Tumor Cells by Primary Lymphocytes Modified with Chimeric T Cell Receptors (2000)

A promising strategy for cancer treatment is adoptive immunotherapy with gene-modified lymphocytes expressing a chimeric T cell receptor (cTCR) that directs tumor targeting and stimulates T cell effector functions. In this study, the activities of two novel cTCR molecules (GAgamma and GAHgamma) were investigated. Both encode a single-chain variable fragment (scFv) derived from the monoclonal antibody (MAb) GA733.2, which binds the epithelial glycoprotein 2 (EGP-2) overexpressed on a variety of human carcinomas. In the GAgamma cTCR, the scFv is directly fused to the transmembrane/cytoplasmic portions of the immunoglobulin Fc receptor (Ig FcRI) gamma subunit, which mediates T cell signaling. GAHgamma possesses an extracellular spacer composed of the CD8alpha immunoglobulin hingelike domain inserted between the scFv and gamma chain. Activated T cells (ATCs), stimulated ex vivo using anti-CD3 MAb, were derived from either healthy donors or patients and transduced with recombinant retrovirus encoding the respective GA cTCR molecules. After culture expansion for 14 days, GAgamma-modified ATCs demonstrated enhanced targeting and lysis of EGP-2+ colon cancer cells and increased cytokine secretion. Cells transduced with the GAHgamma cTCR displayed specific lytic activity that was about twofold greater than that of GAgamma-ATCs and produced significantly more cytokine. In addition, reactivation of GAHgamma-ATC with anti-CD3 MAb prior to addition to EGP-2+ tumor target induced a further increase in lytic activity. Because the activation status influences T cell antitumor functions, our data suggest that reactivation prior to adoptive transfer would improve the clinical efficacy of GAHgamma-modified ATCs.
Structure-function studies of the SERPIN plasminogen activator inhibitor type 1. Analysis of chimeric strained loop mutants (1990)

Three chimeric mutants of plasminogen activator inhibitor 1 (PAI-1) have been constructed where the strained loop of wild type PAI-1 (wtPAI-1) has been replaced with a 19-amino acid region from either plasminogen activator inhibitor 2 (PAI-2), antithrombin III, or with an artificial serine protease inhibitor superfamily consensus strained loop. The inhibitors were expressed in Escherichia coli, and the purified proteins had specific activities toward urokinase-type plasminogen activator (uPA) or the single- and two-chain forms of tissue type plasminogen activator (tPA) that were similar to wtPAI-1. Experiments suggest that the strained loop of PAI-1 is not responsible for the transition between the latent and the active conformations or for binding to vitronectin. Second-order rate constants for the interactions with uPA and single- or two-chain tPA were similar to those of wtPAI-1. Values range from a low of 1.8 x 10(5) M-1 s-1 for the interaction of the PAI-2 chimera with single-chain tPA to a high value of 1.6 x 10(7) M-1 s-1 for the consensus mutant with two-chain tPA. This former value is 200 times higher than the reported rate constant for the interaction between PAI-2 and single-chain tPA, suggesting that structures outside of the strained loop are responsible for the major differences in specificity between PAI-1 and PAI-2.
An algorithm for the T-count (2013)

We consider quantum circuits composed of Clifford and T gates. In this context the T gate has a special status since it confers universal computation when added to the (classically simulable) Clifford gates. However it can be very expensive to implement fault-tolerantly. We therefore view this gate as a resource which should be used only when necessary. Given an n-qubit unitary U we are interested in computing a circuit that implements it using the minimum possible number of T gates (called the T-count of U). A related task is to decide if the T-count of U is less than or equal to m; we consider this problem as a function of N=2^n and m. We provide a classical algorithm which solves it using time and space both upper bounded as O(N^m poly(m,N)). We implemented our algorithm and used it to show that any Clifford+T circuit for the Toffoli or the Fredkin gate requires at least 7 T gates. This implies that the known 7 T gate circuits for these gates are T-optimal. We also provide a simple expression for the T-count of single-qubit unitaries.
CGH, cDNA and Tissue Microarray Analyses Implicate FGFR2 Amplification in a Small Subset of Breast Tumors (2001)

Multiple regions of the genome are often amplified during breast cancer development and progression, as evidenced in a number of published studies by comparative genomic hybridization (CGH). However, only relatively few target genes for such amplifications have been identified. Here, we indicate how small-scale commercially available cDNA and CGH microarray formats combined with the tissue microarray technology enable rapid identification of putative amplification target genes as well as analysis of their clinical significance. According to CGH, the SUM-52 breast cancer cell line harbors several high-level DNA amplification sites, including the 10q26 chromosomal region where the fibroblast growth factor receptor 2 (FGFR2) gene has been localized. High level amplification of FGFR2 in SUM-52 was identified using CGH analysis on a microarray of BAC clones. A cDNA microarray survey of 588 genes showed >40-fold overexpression of FGFR2. Finally, a tissue microarray based FISH analysis of 750 uncultured primary breast cancers demonstrated in vivo amplification of the FGFR2 gene in about 1% of the tumors. In conclusion, three consecutive microarray (CGH, cDNA and tissue) experiments revealed high-level amplification and overexpression of the FGFR2 in a breast cancer cell line, but only a low frequency of involvement in primary breast tumors. Applied to a genomic scale with larger arrays, this strategy should facilitate identification of the most important target genes for cytogenetic rearrangements, such as DNA amplification sites detected by conventional CGH. Figures on http://www.esacp.org/acp/2001/22-4/heiskanen.htm
The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue (2001)

have decreased levels of UCP1, the mitochondrial protein that shunts the energy derived from mitochondrial fatty acid oxidation from ATP formation to thermogenesis (1,11,(15)(16)(17)(18).Physiological replacement of T4, but not T3, rapidly restores adrenergic responsiveness, UCP1 gene expression, and BAT thermogenesis by a mechanism that is blocked by iopanoic acid (IOP).This is explained by the high D2 activity in hypothyroid BAT, which catalyzes the activation of T4 to T3 (5, 11).This compensates for the fall in circulating T4, since administration of only small amount of T4 to hypothyroid rats (only 25% of the daily replacement dose) increases BAT TR occupancy to about 50%, almost exclusively due to locally generated T3 (19).Recent studies indicate that the TR1 isoform is required to maintain the normal adrenergic responsiveness of the brown adipocytes whereas TR mediates T3induced UCP1 gene expression (20).It is the adrenergic pathway that mediates the three-to fourfold increase in the activity of lipogenic enzymes observed in this tissue during cold exposure.In isolated brown adipocytes, NE stimulates lipogenesis only in the presence of T4, in which case it is blocked by pretreatment with IOP (21).Thus it is reasonable to hypothesize that D2 is required to generate the T3 from T4, which permits the normal acute thermogenic function of BAT to occur.
Cyclic Adenosine Monophosphate in Acute Myocardial Infarction With Heart Failure (2006)

yclic adenosine monophosphate (cAMP) is a tightly regulated second messenger that is critically involved in many intracellular processes. In cardiomyocytes, the activation of a number of membrane receptors, notably -receptors and muscarinic receptors, acts through stimulatory or inhibitory G-proteins (Gs/Gi) on adenylyl cyclase (AC), which synthesizes cAMP from ATP. cAMP is degraded by phosphodiesterases (PDE). Thereafter, cAMP activates protein kinase A (PKA), which, in turn, through phosphorylation of L-type calcium channels, ryanodine receptors, phospholamban, and troponin I, improves excitationcontraction coupling and increases heart rate, as well as contraction amplitude and relaxation. PKA also phosphorylates nuclear cAMP-response element binding proteins to activate transcription. 1 There are at least 9 isoforms of AC; the mammalian myocardium expresses mainly AC V and VI. AC V is the predominant isoform in adult cardiac tissue, whereas AC VI expression decreases with age. Both isoforms are phosphorylated by PKA and thereby inhibited, thus providing a feedback regulation and potential desensitization pathway. 2,3 Transgenic mice with cardiac-directed overexpression of AC VI have normal cAMP and cardiac function at rest but increased responses in both cAMP and function to -adrenergic stimulation, 4 as confirmed in the present study by Takahasi et al.
Three‐dimensional high frequency power Doppler ultrasonography for the assessment of microvasculature during fracture healing in a rat model (2011)

Abstract We aimed to establish a novel approach with 3D high frequency power Doppler ultrasonography (3D‐HF‐PDU) to assess microvasculature at the fracture site in rat femurs by comparing with microCT‐based microangiography. Twenty‐four 9‐month‐old ovariectomized (OVX) osteoporotic rats and age‐matched sham‐ovariectomized (Sham) rats were used for establishing closed fracture models on right femora. At 2, 4, and 8 weeks post‐operatively, four rats in each group underwent in vivo 3D‐HF‐PDU scanning for evaluation of vascularization and blood flow at the fracture site. Then the fractured femora were harvested for ex vivo microangiography, and neovasculatures within the callus were reconstructed for vascular volume analysis. Correlation between the vascular volumes of the two methodologies was examined. Both 3D‐HF‐PDU and microangiography showed a decline of vascular volume at the fracture site from 2 to 8 weeks and a significantly larger volume in the Sham group than the OVX group. A significant linear positive correlation ( r = 0.87, p &lt; 0.001) was detected between the volumes measured by the two methodologies. Osteoporotic rats had a diminished angiogenic response and lower blood perfusion than Shams. We believe 3D‐HF‐PDU is feasible and reproducible for in vivo assessment of microvasculature during femoral fracture healing in rats. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:137–143, 2012
Sun Coke Company's heat recovery cokemaking technology. High coke quality and low environmental impact (2003)

Sun Coke Company's heat recovery cokemaking technology has been developed over the past 40 years, and is now poised to become the dominant technology to meet future global cokemaking needs. An extensive data base regarding coal blends tested and resultant coke quality will be presented. On the environmental front, extensive air emission data has been collected and will be compared to by-product coke plant air emission data.