gebhart/patrepeval huggingface dataset:
A Computational Study of Feedback Effects on Signal Dynamics in a Mitogen‐Activated Protein Kinase (MAPK) Pathway Model (2001)

Exploiting signaling pathways for the purpose of controlling cell function entails identifying and manipulating the information content of intracellular signals. As in the case of the ubiquitously expressed, eukaryotic mitogen-activated protein kinase (MAPK) signaling pathway, this information content partly resides in the signals' dynamical properties. Here, we utilize a mathematical model to examine mechanisms that govern MAPK pathway dynamics, particularly the role of putative negative feedback mechanisms in generating complete signal adaptation, a term referring to the reset of a signal to prestimulation levels. In addition to yielding adaptation of its direct target, feedback mechanisms implemented in our model also indirectly assist in the adaptation of signaling components downstream of the target under certain conditions. In fact, model predictions identify conditions yielding ultra-desensitization of signals in which complete adaptation of target and downstream signals culminates even while stimulus recognition (i.e., receptor-ligand binding) continues to increase. Moreover, the rate at which signal decays can follow first-order kinetics with respect to signal intensity, so that signal adaptation is achieved in the same amount of time regardless of signal intensity or ligand dose. All of these features are consistent with experimental findings recently obtained for the Chinese hamster ovary (CHO) cell lines (Asthagiri et al., J. Biol. Chem. 1999, 274, 27119-27127). Our model further predicts that although downstream effects are independent of whether an enzyme or adaptor protein is targeted by negative feedback, adaptor-targeted feedback can "back-propagate" effects upstream of the target, specifically resulting in increased steady-state upstream signal. Consequently, where these upstream components serve as nodes within a signaling network, feedback can transfer signaling through these nodes into alternate pathways, thereby promoting the sort of signaling cross-talk that is becoming more widely appreciated.
Optimal Electrode Size for Multi-Scale Extracellular-Potential Recording From Neuronal Assemblies (2019)

Advances in microfabrication technology have enabled the production of devices containing arrays of thousands of closely spaced recording electrodes, which afford subcellular resolution of electrical signals in neurons and neuronal networks. Rationalizing the electrode size and configuration in such arrays demands consideration of application-specific requirements and inherent features of the electrodes. Tradeoffs among size, spatial density, sensitivity, noise, attenuation, and other factors are inevitable. Although recording extracellular signals from neurons with planar metal electrodes is fairly well established, the effects of the electrode characteristics on the quality and utility of recorded signals, especially for small, densely packed electrodes, have yet to be fully characterized. Here, we present a combined experimental and computational approach to elucidating how electrode size, and size-dependent parameters, such as impedance, baseline noise, and transmission characteristics, influence recorded neuronal signals. Using arrays containing platinum electrodes of different sizes, we experimentally evaluated the electrode performance in the recording of local field potentials (LFPs) and extracellular action potentials (EAPs) from the following cell preparations: acute brain slices, dissociated cell cultures, and organotypic slice cultures. Moreover, we simulated the potential spatial decay of point-current sources to investigate signal averaging using known signal sources. We demonstrated that the noise and signal attenuation depend more on the electrode impedance than on electrode size, <i>per se</i>, especially for electrodes <10 μm in width or diameter to achieve high-spatial-resolution readout. By minimizing electrode impedance of small electrodes (<10 μm) via surface modification, we could maximize the signal-to-noise ratio to electrically visualize the propagation of axonal EAPs and to isolate single-unit spikes. Due to the large amplitude of LFP signals, recording quality was high and nearly independent of electrode size. These findings should be of value in configuring <i>in vitro</i> and <i>in vivo</i> microelectrode arrays for extracellular recordings with high spatial resolution in various applications.
A Network Virtualization Overlay Solution using EVPN (2014)

This document describes how EVPN can be used as an NVO solution and
explores the various tunnel encapsulation options over IP and their
impact on the EVPN control-plane and procedures. In particular, the
following encapsulation options are analyzed: MPLS over GRE, VXLAN,
and NVGRE.
Synthesis of Imidazo[1,2-a]pyridine C-Nucleosides with an Unexpected Site of Ribosylation (1997)

Several new polychlorinated imidazo[1,2-a]pyridine C-nucleosides have been prepared. Lithiated imidazo[1,2-a]pyridines were condensed with protected ribonolactones, trapped as 1‘-acetoxy derivatives, and these 1‘-acetoxy derivatives were reductively deacetoxylated and deprotected to give C-nucleosides. Long-range proton−carbon decoupling experiments were used to determine the actual site of ribosylation and established that the ribose moiety was unexpectedly attached to the C5 position of the imidazo[1,2-a]pyridines. This method has provided C-nucleosides, such as 2,6-dichloro-5-(β-d-ribofuranosyl)imidazo[1,2-a]pyridine and 2,6,7-trichloro-5-(β-d-ribofuranosyl)imidazo[1,2-a]pyridine and the corresponding α-products.
The Bridge Builders of Luther Memorial (2002)

The congregation of Luther Memorial Church in Des Moines, Iowa, celebrated its centennial anniversary in 1999, during which time there was a good deal of reflection concerning the historical roots and activities of the church during the preceding one hundred years. Much of the early history of the congregation was closely associated with Grand View College. During the first decades, the school provided worship facilities as well as the pastor services for the emerging congregation. With financial support from the Danish Evangelical Lutheran Church, a building was erected in 1917, which has served as the home for the congregation since that time.
XML Bible (1999)

From the Publisher:
Now revised and expanded to cover the latest XML technologies and applications, this all-in-one tutorial and reference shows you step by step how to put the power of XML to work in your Web pages. From document type definitions and style sheets to XPointers, schemas, the Wireless Markup Language, XHTML and other advanced tools and applications, XML expert Elliotte Rusty Harold gives you all the know-how and examples you need to integrate XML with HTML, solve real-world development challenges, and create data-driven content.--BOOK JACKET.
Three human transforming genes are related to the viral ras oncogenes. (1983)

Three distinct transforming genes present in human tumor cell lines are all related to the viral oncogenes of Harvey and Kirsten murine sarcoma viruses, designated v-H-ras and v-K-ras, respectively. The transforming gene of a bladder carcinoma cell line has been shown to be a human homolog to v-H-ras [Parada, L. F., Tabin, C. J., Shih, C. & Weinberg, R. A. (1982) Nature (London) 297, 474-478; Santos, E., Tronick, S. R., Aaronson, S. A., Pulciani, S. & Barbacid, M. (1982) Nature (London) 298, 343-347]. The transforming gene common to one colon (SK-CO-1) and two lung carcinoma (SK-LU-1 and Calu-1) cell lines is the same human homolog of v-K-ras as is the transforming gene previously identified in a lung carcinoma cell line Lx-1 [Der, C. J., Krontiris, T. G. & Cooper, G. M. (1982) Proc. Natl. Acad. Sci. USA 79, 3637-3640]. The transforming gene of SK-N-SH neuroblastoma cells is weakly homologous to both v-H-ras and v-K-ras. NIH 3T3 cells transformed with the SK-N-SH transforming gene contain increased levels of a protein serologically and structurally related to the protein products of the v-H-ras and v-K-ras genes. Therefore, it represents a third member of the ras gene family, which we have called N-ras. Based on the homology with the v-ras genes, we have established the orientation of transcription and approximate coding regions of the cloned human K-ras and N-ras genes.
Human deoxycytidine kinase is located in the cell nucleus (1997)

Human deoxyribonucleoside kinases are required for the pharmacological activity of several clinically important anticancer and antiviral nucleoside analogs. Human deoxycytidine kinase and thymidine kinase 1 are described as cytosolic enzymes in the literature, whereas human deoxyguanosine kinase and thymidine kinase 2 are believed to be located in the mitochondria. We expressed the four human deoxyribonucleoside kinases as fusion proteins with the green fluorescent protein to study their intracellular locations in vivo. Our data showed that the human deoxycytidine kinase is located in the cell nucleus and the human deoxyguanosine kinase is located in the mitochondria. The fusion proteins between green fluorescent protein and thymidine kinases 1 and 2 were both predominantly located in the cytosol. Site-directed mutagenesis of a putative nuclear targeting signal, identified in the primary structure of deoxycytidine kinase, completely abolished nuclear import of the protein. Reconstitution of a deoxycytidine kinase-deficient cell line with the wild-type nuclear or the mutant cytosolic enzymes both restored sensitivity toward anticancer nucleoside analogs. This paper reports that a deoxyribonucleoside kinase is located in the cell nucleus and we discuss the implications for deoxyribonucleotide synthesis and phosphorylation of nucleoside analogs.
Single-qubit gates in frequency-crowded transmon systems (2013)

Recent experimental work on superconducting transmon qubits in three-dimensional (3D) cavities shows that their coherence times are increased by an order of magnitude compared to their two-dimensional cavity counterparts. However, to take advantage of these coherence times while scaling up the number of qubits it is advantageous to address individual qubits which are all coupled to the same 3D cavity fields. The challenge in controlling this system comes from spectral crowding, where the leakage transition of qubits is close to computational transitions in other qubits. Here, it is shown that fast pulses are possible which address single qubits using two-quadrature control of the pulse envelope, while the derivative removal by adiabatic gate method of Motzoi et al. [Phys. Rev. Lett. 103, 110501 (2009)] alone only gives marginal improvements over the conventional Gaussian pulse shape. On the other hand, a first-order result using the Magnus expansion gives a fast analytical pulse shape which gives a high-fidelity gate for a specific gate time, up to a phase factor on the second qubit. Further numerical analysis corroborates these results and yields to even faster gates, showing that leakage-state anharmonicity does not provide a fundamental quantum speed limit.
Equation of state for small, large, polydisperse, and associating molecules: extension to fluid mixtures (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEquation of state for small, large, polydisperse, and associating molecules: extension to fluid mixturesStanley H. Huang and Maciej RadoszCite this: Ind. Eng. Chem. Res. 1991, 30, 8, 1994–2005Publication Date (Print):August 1, 1991Publication History Published online1 May 2002Published inissue 1 August 1991https://pubs.acs.org/doi/10.1021/ie00056a050https://doi.org/10.1021/ie00056a050research-articleACS PublicationsRequest reuse permissionsArticle Views2539Altmetric-Citations771LEARN 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
Vaccinia virus transcription (2003)

Vaccinia virus replication takes place in the cytoplasm of the host cell. The nearly 200 kbp genome owes part of its complexity to encoding most of the proteins involved in genome and mRNA synthesis. The multisubunit vaccinia virus RNA polymerase requires a separate set of virus-encoded proteins for the transcription of the early, intermediate and late classes of genes. Cell fractionation studies have provided evidence for a role for host cell proteins in the initiation and termination of vaccinia virus intermediate and late gene transcription. Vaccinia virus resembles nuclear DNA viruses in the integration of viral and host proteins for viral mRNA synthesis, yet is markedly less reliant on host proteins than its nuclear counterparts.
A novel endothelial cell molecule mediating lymphocyte binding in humans. (1993)

Leukocyte extravasation is critically dependent on proper interactions between leukocytes and vascular endothelial cells. Although several molecules mediating these interactions have been identified, all the homing phenomena observed in vivo cannot be explained on the basis of the known adhesion molecules. To discover novel molecules involved in leukocyte migration we have made monoclonal antibodies against human endothelial cells. With the help of one such monoclonal antibody a novel endothelial cell molecule called vascular adhesion protein-1 (VAP-1) was found. Uniqueness of VAP-1 is evident on the basis of its expression pattern, molecular mass, functional properties and N-terminal amino acid sequence. VAP-1 mediates lymphocyte binding to endothelium in peripheral lymph nodes, tonsil and inflamed synovium. Therefore, VAP-1 is relevant to understanding of the physiologic and pathologic lymphocyte migration in man, and may be valuable for dissecting the molecular events of tissue-selective lymphocyte homing.
Inhibition of tumor induction in two-stage carcinogenesis on mouse skin. (1969)

The inhibition of tumorigenesis by various agents possessing known biochemical and/or biologic effects has been examined using mouse skin initiation-promotion experiments. The agents were applied on mouse skin at various time intervals with respect to the initiating treatment with 7,12-dimethylbenz(a)anthracene. Actinomycin D and aflatoxin B1 were most effective 30 and 7 days after initiation respectively. On the other hand, dl -diepoxybutane and acridine orange were most effective when applied at the time of initiation. The different agents probably act by several mechanisms, and the same agent may inhibit tumorigenesis in different ways depending on the time of application with respect to initiation. It is proposed that actinomycin D interferes selectively with initiated or preneoplastic cells and that initiation represents a complex sequential biochemical process.
Inhibition of GM-CSF Receptor Function by Stable RNA Interference in a NOD/SCID Mouse Hematopoietic Stem Cell Transplantation Model (2003)

RNA interference (RNAi) describes a highly conserved mechanism of sequence-specific posttranscriptional gene silencing triggered by double-stranded RNA (dsRNA). Whereas RNAi is applied to study gene function in different organisms and in variant cell types, little is known about RNAi in human hematopoietic stem and progenitor cells and their myeloid progeny. To address this issue, short hairpin RNAs (shRNA) were designed to target the common beta-chain of the human receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 (betaGMR). These receptors regulate proliferation, survival, differentiation, and functional activity of hematopoietic cells. In addition to markedly inhibiting mRNA and protein expression, anti-beta-GMR shRNAs were also found to inhibit receptor function in a cell culture model. Furthermore, lentiviral gene transfer of shRNA expression cassettes into primary normal CD34+ cells selectively inhibited colony formation of transduced progenitors when stimulated with GM-CSF/IL-3 but not when stimulated with cytokines that do not signal via beta-GMR. Finally, anti-beta-GMR shRNAs had no detectable effect on engraftment or lineage composition of lentivirally transduced human CD34+ cells transplanted into NOD/SCID mice. However, the growth defect of transduced colony-forming cells under stimulation with GM-CSF/IL-3 remains unchanged in bone marrow cells harvested from individual NOD/SCID mice 6 weeks after transplantation. These data indicate that lentiviral gene transfer of shRNA expression cassettes may be used to induce long-term RNAi in human hematopoietic stem and progenitor cells for functional genetics and potential therapeutic intervention.
Characterization of corticotropin‐releasing factor receptor‐mediated adenylate cyclase activity in the rat central nervous system (1987)

We report here that corticotropin-releasing factor (CRF) stimulates adenylate cyclase activity in the rat central nervous system (CNS). In frontoparietal cortex homogenates, the stimulation by CRF was dependent on time, temperature, tissue protein concentration, and guanine nucleotides. The rank order of potency for CRF analogs and fragments in stimulating adenylate cyclase activity [(Nle21,38) rat CRF greater than rat CRF approximately equal to acetyl ovine CRF (4-41) approximately equal to alpha helical ovine CRF greater than ovine CRF much greater than ovine CRF (1-39) approximately equal to ovine CRF (7-41)] was consistent with their affinities for CRF receptors in the brain and their relative potencies in stimulating pituitary adrenocorticotropic hormone secretion in vitro. The putative CRF receptor antagonist, alpha helical ovine CRF (9-41), did not stimulate adenosine 3',5'-cyclic monophosphate (cAMP) production but was able to attenuate the stimulation by various concentrations of rat CRF. The regional distribution of 125I-Tyr(o)-ovine CRF binding (olfactory bulb greater than frontoparietal cortex approximately equal to cerebellum greater than hypothalamus greater than striatum greater than or equal to midbrain greater than hippocampus greater than or equal to spinal cord) did not correspond with the regional degree of CRF receptor-mediated stimulation of adenylate cyclase (frontoparietal cortex greater than olfactory bulb greater than or equal to cerebellum greater than midbrain greater than or equal to hippocampus greater than striatum greater than or equal to hypothalamus greater than spinal cord). In addition, marked differences were observed in the ability of forskolin to potentiate CRF-stimulated cAMP production in the various brain areas examined. In summary, these data demonstrate that at least one of the second-messenger systems mediating the effects of CRF in the CNS involves stimulation of cAMP production and provides further support for a neurotransmitter role for this neuropeptide in the brain. Significant differences in the regulation of CRF-stimulated cAMP production and the disparity between CRF receptor number and receptor-mediated adenylate cyclase activity in discrete regions of the rat CNS suggest that some populations of CRF receptors in the brain may be functionally coupled to alternative signal transduction mechanisms.
Clinical Guideline: Management of Gastroparesis (2012)

This guideline presents recommendations for the evaluation and management of patients with gastroparesis. Gastroparesis is identified in clinical practice through the recognition of the clinical symptoms and documentation of delayed gastric emptying. Symptoms from gastroparesis include nausea, vomiting, early satiety, postprandial fullness, bloating, and upper abdominal pain. Management of gastroparesis should include assessment and correction of nutritional state, relief of symptoms, improvement of gastric emptying and, in diabetics, glycemic control. Patient nutritional state should be managed by oral dietary modifications. If oral intake is not adequate, then enteral nutrition via jejunostomy tube needs to be considered. Parenteral nutrition is rarely required when hydration and nutritional state cannot be maintained. Medical treatment entails use of prokinetic and antiemetic therapies. Current approved treatment options, including metoclopramide and gastric electrical stimulation (GES, approved on a humanitarian device exemption), do not adequately address clinical need. Antiemetics have not been specifically tested in gastroparesis, but they may relieve nausea and vomiting. Other medications aimed at symptom relief include unapproved medications or off-label indications, and include domperidone, erythromycin (primarily over a short term), and centrally acting antidepressants used as symptom modulators. GES may relieve symptoms, including weekly vomiting frequency, and the need for nutritional supplementation, based on open-label studies. Second-line approaches include venting gastrostomy or feeding jejunostomy; intrapyloric botulinum toxin injection was not effective in randomized controlled trials. Most of these treatments are based on open-label treatment trials and small numbers. Partial gastrectomy and pyloroplasty should be used rarely, only in carefully selected patients. Attention should be given to the development of new effective therapies for symptomatic control.
Chemotherapy for pancreatic cancer (2003)

Pancreatic cancer is a common, highly lethal disease that is rising in incidence. Chemotherapy based on 5-fluorouracil (5-FU) has been shown to prolong survival in advanced pancreatic cancer. Gemcitabine improves major symptoms and survival outcomes compared with bolus 5-FU. Many novel small molecules are being widely and actively researched. These compounds are based on classical mechanisms of action as well as biological therapies targeting novel cellular survival pathways, and include fluoropyrimidines, nucleoside cytidine analogues, platinum analogues, topoisomerase-inhibitors, antimicrotubule agents, proteasome inhibitors, vitamin D analogues, arachidonic acid pathway inhibitors, histone deacytylator inhibitors, farnesyltransferase inhibitors and epidermal growth factor receptor therapies. Adjuvant chemotherapy has also demonstrated the best survival outcomes following resection compared to other adjuvant or neo-adjuvant strategies such as radiation-based treatments. These benefits are superimposed on the dramatic increase in resectability rates and reduction in post-operative mortality achieved by centralisation of treatment in high-volume speciality centres. Newer 'small-molecule' drugs as well as the latest 'large-molecule' biological agents hold considerable promise for the future. Real advances are anticipated over the next five years but are dependent on large randomised controlled trials for success.
Frequency planning for nonlinear distortion reduction in wideband transmission (1991)

A frequency planning scheme for nonlinear distortion reduction in video transmission systems is presented. The scheme is suitable for wideband application because it is not limited by electronic circuits. For this frequency planning algorithm, experimental data showed a third order distortion reduction of 14 to 16 dB.