gebhart/patrepeval huggingface dataset:
Modular Extracellular Sensor Architecture for Engineering Mammalian Cell-based Devices (2014)

Engineering mammalian cell-based devices that monitor and therapeutically modulate human physiology is a promising and emerging frontier in clinical synthetic biology. However, realizing this vision will require new technologies enabling engineered circuitry to sense and respond to physiologically relevant cues. No existing technology enables an engineered cell to sense exclusively extracellular ligands, including proteins and pathogens, without relying upon native cellular receptors or signal transduction pathways that may be subject to crosstalk with native cellular components. To address this need, we here report a technology we term a Modular Extracellular Sensor Architecture (MESA). This self-contained receptor and signal transduction platform is maximally orthogonal to native cellular processes and comprises independent, tunable protein modules that enable performance optimization and straightforward engineering of novel MESA that recognize novel ligands. We demonstrate ligand-inducible activation of MESA signaling, optimization of receptor performance using design-based approaches, and generation of MESA biosensors that produce outputs in the form of either transcriptional regulation or transcription-independent reconstitution of enzymatic activity. This systematic, quantitative platform characterization provides a framework for engineering MESA to recognize novel ligands and for integrating these sensors into diverse mammalian synthetic biology applications.
Inhibitory Effect of Baicalein, a Flavonoid in Scutellaria Root, on Eotaxin Production by Human Dermal Fibroblasts (2001)

Eotaxin is an eosinophil-specific chemokine associated with the recruitment of eosinophils to sites of allergic inflammation. "Saiboku-to" (Formula magnoliae et bupleuri) is a kampo herbal medicine used for the treatment of bronchial asthma in Japan. In this study, we investigated the effects of Scutellaria Root, a major herb in Saiboku-to and its components such as baicalein and baicalin on eotaxin production by IL-4 plus TNF-alpha-stimulated human fibroblasts. An extract of Scutellaria Root markedly inhibited eotaxin production. Four major flavonoids from Scutellaria Root were found to show inhibitory activity on eotaxin production at a concentration of 10 micrograms/ml in the order of baicalein > oroxylin A > baicalin > skullcapflavon II. The inhibitory effect of baicalein was expressed in a dose-dependent manner, and almost 50% inhibition was observed at 1.8 micrograms/ml. Furthermore, baicalein prevented human eotaxin mRNA expression in IL-4 plus TNF-alpha-stimulated human fibroblasts. These results help explain the pharmacological efficacy of Scutellaria Root in the treatment of bronchial asthma since it would suppress eotaxin associated recruitment of eosinophils.
EXPRESSION OF MxA PROTEIN IN BLOOD LYMPHOCYTES OF CHILDREN RECEIVING ANTICANCER CHEMOTHERAPY (2006)

The aim of the study was to evaluate whether IFN-alpha/beta-inducible MxA protein expression in children receiving anticancer treatment can be used as an indicator for virus infections during the febrile episodes. Twenty-six children with mainly hematological malignancies entered the study. Children with laboratory-confirmed virus infections had clearly elevated MxA protein levels compared to their counterparts with bacterial or unknown etiology. MxA protein expression increased moderately following the administration of cytostatic agents, even though these children had no clinical signs of infection.
Thermal diffusivity effect in opto-thermal skin measurements (2010)

We present our latest study on the thermal diffusivity effect in opto-thermal skin measurements. We discuss how thermal diffusivity affects the shape of opto-thermal signal, and how to measure thermal diffusivity in opto-thermal measurements of arbitrary sample surfaces. We also present a mathematical model for a thermally gradient material, and its corresponding opto-thermal signal. Finally, we show some of our latest experimental results of this thermal diffusivity effect study.
Finding fusion genes resulting from chromosome rearrangement by analyzing the expressed sequence databases (2004)

Chromosomal rearrangements resulting in gene fusions are frequently involved in carcinogenesis. Here, we describe a semiautomatic procedure for identifying fusion gene transcripts by using publicly available mRNA and EST databases. With this procedure, we have identified 96 transcript sequences that are derived from 60 known fusion genes. Also, 47 or more additional sequences appear to be derived from 20 or more previously unknown putative fusion genes. We have experimentally verified the presence of a previously unknown IRA1/RGS17 fusion in the breast cancer cell line MCF7. The fusion gene encodes the full-length RGS17 protein, a regulator of G protein-coupled signaling, under the control of the IRA1 gene promoter. This study demonstrates that databases of ESTs can be used to discover fusion genes resulting from structural rearrangement of chromosomes.
Human Lung Fibroblast-Derived Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Mediates Eosinophil Survival In Vitro (1989)

Tissue eosinophilia has been reported to occur in pulmonary fibrosis, a disease characterized by chronic inflammation and lung fibroblast proliferation. We have examined the in vitro interaction of these two cell types by determining the in vitro survival of human peripheral blood eosinophils co-cultured with human lung fibroblasts. Survival of eosinophils cultured alone was 10% at day 3 and less than 1% at day 7. In contrast, survival of eosinophils that had been co-cultured with fibroblasts was 98, 90, 73, and 69% at days 3, 7, 10, and 14, respectively. Fibroblast-conditioned medium (CM) elicited a similar result in a dose-dependent fashion. Survival of eosinophils cultured with CM which had been preincubated with a monoclonal-neutralizing antibody to human GM-CSF was inhibited in a dose-dependent manner. Human recombinant-derived GM-CSF supported eosinophil survival in the dose-dependent fashion. Survival at day 7 of eosinophils treated with one single dose of GM-CSF (10 U/ml) was 64%. The effect of fibroblast-CM on eosinophils likely represents true survival since eosinophil proliferation as determined by [3H]thymidine incorporation did not occur. We also report that freshly isolated eosinophils had normal ultrastructural, scanning and transmission electron microscopy characteristics, and were normodense. In contrast, eosinophils co-cultured for 7 days with fibroblasts acquired irregular shapes and became hypodense and partially degranulated. Thus, our results indicate that human lung fibroblast-derived GM-CSF mediates the in vitro survival of human eosinophils.(ABSTRACT TRUNCATED AT 250 WORDS)
Interaction of neutral polysaccharides with phosphatidylcholine multilamellar liposomes. Phase transitions studied by the binding of fluorescein-conjugated dextrans (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInteraction of neutral polysaccharides with phosphatidylcholine multilamellar liposomes. Phase transitions studied by the binding of fluorescein-conjugated dextransMaurizio Minetti, Patrizia Aducci, and Vincenza VitiCite this: Biochemistry 1979, 18, 12, 2541–2548Publication Date (Print):June 12, 1979Publication History Published online1 May 2002Published inissue 12 June 1979https://pubs.acs.org/doi/10.1021/bi00579a017https://doi.org/10.1021/bi00579a017research-articleACS PublicationsRequest reuse permissionsArticle Views161Altmetric-Citations24LEARN 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
Interfacing an automatic elemental analyser with an isotope ratio mass sepectrometer: the potential for fully automated total nitrogen and nitrogen-15 analysis (1983)

An interface between an automatic nitrogen analyser and an isotope mass spectrometer is described. The interface enables total nitrogen analyses and nitrogen isotope ratio measurements to be made semi-automatically, at the rate of 12 h–1. The precision of the measurements was at the detection limit of the mass spectrometer (0.00026 atom-%15N; ±0.7‰). No significant cross-contamination between samples was observed (<0.02% carry over). The potential for full automation and extension of the interface for other stable isotope measurements is discussed.
Distribution systems loss minimum re-configuration by simulated annealing method (1991)

A distribution systems loss minimum reconfiguration method by simulated annealing is proposed. The loss minimum problem is a complex mixed integer programming problem and is very difficult to solve by a mathematical programming approach. A simulated annealing method is an optimization method based on an analogy between physical multi-particle system and a combinatorial optimization problem. Therefore, a global minimum of a combinatorial optimization problem can be found with high probability through a careful annealing process. Numerical examples demonstrate the validity and effectiveness of the proposed method. >
The VOYAGER speech understanding system: preliminary development and evaluation (2002)

Early experience with the development of the MIT VOYAGER spoken language system is described, and its current performance is documented. The three components of VOYAGER, the speech recognition component, the natural language component, and the application back-end, are described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
RecA stimulates sister chromatid exchange and the fidelity of double-strand break repair, but not gene targeting, in plants transformed by Agrobacterium (2000)

Expression of the bacterial RecA protein in plants stimulates homologous recombination in tobacco. Here we show that RecA plays a direct role in DNA strand exchange in vivo. The number of sister chromatid exchanges (SCEs) was increased 2.4-fold over wild type in transgenic tobacco plants expressing a nuclear-targeted RecA (nt-RecA) protein and could not be increased further by DNA damage, which caused a doubling of the baseline SCE frequency in wild-type plants. Although gene targeting requires homologous recombination, the number of targeted gene replacements was not increased markedly by the presence of nt-RecA by using Agrobacterium-mediated transformation. However, the number of double-strand breaks that were repaired at both sides by homologous recombination was increased 3.3-fold. Stimulation of SCE and fidelity of double-strand break repair by nt-RecA, but not by gene targeting, suggests that the stimulatory activity of RecA is linked to active DNA synthesis. Therefore, nascent replication-associated single strands may be a prerequisite for RecA action in plant cells.
The roles of the classical and alternative nuclear factor-kappaB pathways: potential implications for autoimmunity and rheumatoid arthritis (2008)

Nuclear factor-kappaB (NF-kappaB) is an inducible transcription factor controlled by two principal signaling cascades, each activated by a set of signal ligands: the classical/canonical NF-kappaB activation pathway and the alternative/noncanonical pathway. The former pathway proceeds via phosphorylation and degradation of inhibitor of NF-kappaB (IkappaB) and leads most commonly to activation of the heterodimer RelA/NF-kappaB1(p50). The latter pathway proceeds via phosphorylation and proteolytic processing of NF-kappaB2 (p100) and leads to activation, most commonly, of the heterodimer RelB/NF-kappaB2 (p52). Both pathways play critical roles at multiple levels of the immune system in both health and disease, including the autoimmune inflammatory response. These roles include cell cycle progression, cell survival, adhesion, and inhibition of apoptosis. NF-kappaB is constitutively activated in many autoimmune diseases, including diabetes type 1, systemic lupus erythematosus, and rheumatoid arthritis (RA). In this review we survey recent developments in the involvement of the classical and alternative pathways of NF-kappaB activation in autoimmunity, focusing particularly on RA. We discuss the involvement of NF-kappaB in self-reactive T and B lymphocyte development, survival and proliferation, and the maintenance of chronic inflammation due to cytokines such as tumor necrosis factor-alpha, IL-1, IL-6, and IL-8. We discuss the roles played by IL-17 and T-helper-17 cells in the inflammatory process; in the activation, maturation, and proliferation of RA fibroblast-like synovial cells; and differentiation and activation of osteoclast bone-resorbing activity. The prospects of therapeutic intervention to block activation of the NF-kappaB signaling pathways in RA are also discussed.
Dynamic analysis of MAPK signaling using a high-throughput microfluidic single-cell imaging platform (2009)

Cells have evolved biomolecular networks that process and respond to changing chemical environments. Understanding how complex protein interactions give rise to emergent network properties requires time-resolved analysis of cellular response under a large number of genetic perturbations and chemical environments. To date, the lack of technologies for scalable cell analysis under well-controlled and time-varying conditions has made such global studies either impossible or impractical. To address this need, we have developed a high-throughput microfluidic imaging platform for single-cell studies of network response under hundreds of combined genetic perturbations and time-varying stimulant sequences. Our platform combines programmable on-chip mixing and perfusion with high-throughput image acquisition and processing to perform 256 simultaneous time-lapse live-cell imaging experiments. Nonadherent cells are captured in an array of 2,048 microfluidic cell traps to allow for the imaging of eight different genotypes over 12 h and in response to 32 unique sequences of stimulation, generating a total of 49,000 images per run. Using 12 devices, we carried out >3,000 live-cell imaging experiments to investigate the mating pheromone response in Saccharomyces cerevisiae under combined genetic perturbations and changing environmental conditions. Comprehensive analysis of 11 deletion mutants reveals both distinct thresholds for morphological switching and new dynamic phenotypes that are not observed in static conditions. For example, kss1Delta, fus3Delta, msg5Delta, and ptp2Delta mutants exhibit distinctive stimulus-frequency-dependent signaling phenotypes, implicating their role in filtering and network memory. The combination of parallel microfluidic control with high-throughput imaging provides a powerful tool for systems-level studies of single-cell decision making.
The Dormancy Dilemma: Quiescence versus Balanced Proliferation (2013)

Metastatic dissemination with subsequent clinical outgrowth leads to the greatest part of morbidity and mortality from most solid tumors. Even more daunting is that many of these metastatic deposits silently lie undetected, recurring years to decades after primary tumor extirpation by surgery or radiation (termed metastatic dormancy). As primary tumors are frequently curable, a critical focus now turns to preventing the lethal emergence from metastatic dormancy. Current carcinoma treatments include adjuvant therapy intended to kill the cryptic metastatic tumor cells. Because such standard therapies mainly kill cycling cells, this approach carries an implicit assumption that metastatic cells are in the mitogenic cycle. Thus, the pivotal question arises as to whether clinically occult micrometastases survive in a state of balanced proliferation and death, or whether these cells undergo at least long periods of quiescence marked by cell-cycle arrest. The treatment implications are thus obvious--if the carcinoma cells are cycling then therapies should target cycling cells, whereas if cells are quiescent then therapies should either maintain dormancy or be toxic to dormant cells. Because this distinction is paramount to rational therapeutic development and administration, we investigated whether quiescence or balanced proliferation is the most likely etiology underlying metastatic dormancy. We recently published a computer simulation study that determined that balanced proliferation is not the likely driving force and that quiescence most likely participates in metastatic dormancy. As such, a greater emphasis on developing diagnostics and therapeutics for quiescent carcinomas is needed.
Contract Costs and Financing Decisions (1990)

Like bondholders, most agents contract for fixed payoffs. Thus, corporate capital structures, which are less than 50 percent debt, are less levered than overall contract structures, in which about 90 percent of total flows are fixed payoffs. The hypothesis analyzed here is that loans and bonds lower contract costs by delegating the monitoring and bonding of the default risks of fixed payoffs to credible specialists (financial intermediaries, bond-holder trustees, rating agencies, and auditors). Other agents can then focus on their specialties, that is, efficient supply of labor, materials, and other services, and the contract problems of these specialties. Copyright 1990 by the University of Chicago.
The Mips R10000 superscalar microprocessor (1996)

The Mips R10000 is a dynamic, superscalar microprocessor that implements the 64-bit Mips 4 instruction set architecture. It fetches and decodes four instructions per cycle and dynamically issues them to five fully-pipelined, low-latency execution units. Instructions can be fetched and executed speculatively beyond branches. Instructions graduate in order upon completion. Although execution is out of order, the processor still provides sequential memory consistency and precise exception handling. The R10000 is designed for high performance, even in large, real-world applications with poor memory locality. With speculative execution, it calculates memory addresses and initiates cache refills early. Its hierarchical, nonblocking memory system helps hide memory latency with two levels of set-associative, write-back caches.
Synthetic vaccines: synthesis of a dimeric Tn antigen-lipopeptide conjugate that elicits immune responses against Tn-expressing glycoproteins (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthetic vaccines: synthesis of a dimeric Tn antigen-lipopeptide conjugate that elicits immune responses against Tn-expressing glycoproteinsTatsushi Toyokuni, Barbara Dean, Shaopei Cai, Diane Boivin, Senitiroh Hakomori, and Anil K. SinghalCite this: J. Am. Chem. Soc. 1994, 116, 1, 395–396Publication Date (Print):January 1, 1994Publication History Published online1 May 2002Published inissue 1 January 1994https://pubs.acs.org/doi/10.1021/ja00080a055https://doi.org/10.1021/ja00080a055research-articleACS PublicationsRequest reuse permissionsArticle Views484Altmetric-Citations84LEARN 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 (3)»Supporting Information Supporting Information Get e-Alerts
Ferroelectric Liquid Crystals. Part 9. Laterally substituted phenyl benzoates incorporating a trans‐1,4‐disubstituted cyclohexane ring (1989)

Abstract About 65 diverse phenyl benzoates incorporating a trans ‐1,4‐disubstituted cyclohexane ring and at least one lateral substituent have been synthesised. The dependence of the liquid‐crystal transition temperatures of these materials on various lateral substituents (F, Cl, CN, and Br) in different positions of the esters has been investigated systematically. The influence of up to four F‐atoms in various positions of a standard ester has been thoroughly studied and the optimum combination for a broad smectic C mesomorphic range established. In consequence, three homologous series incorporating the 4‐alkoxy‐2,3‐difluorobenzoic‐acid moiety were prepared. An additional CC bond was introduced into the alkyl chain attached to the cyclohexane ring of some of these esters and the resulting modifications of the transition temperatures determined. Three ester series incorporating a lateral substituent and the optically active (+)‐( S )‐(1‐methylheptyl)oxy substituent have also been synthesised, and similar effects have been observed. These materials can be used as important components of commercial chiral smectic C mixtures for electro‐optic display device applications.
Catch Me If You Can: Isolating Circulating Tumor Cells from Flowing Blood (2012)

Since the discovery that the concentration of circulating tumor cells (CTCs) in blood is a strong predictor of survival rate in metastatic breast cancer (1), there has been great enthusiasm for the potential of these cells as a marker for cancer progression. The technical challenge is to isolate these rare cells (1–100 cells/mL) from whole blood with sufficient sensitivity and specificity, while maintaining cell viability for postcapture analysis. The most widespread methods of CTC isolation are based on immunocapture of antigens highly expressed on CTCs. Epithelial cell adhesion molecule and prostate-specific membrane antigen are the most extensively characterized antigens used for immunologic detection of carcinomas (2). These antigens are often used in conjunction with cytokeratin, an epithelial marker, to discriminate CTCs from leukocytes.

Immunocapture methods can be divided into bead-based approaches and microfluidic approaches. In bead-based approaches, antibody-coated magnetic nanoparticles bind to CTCs in a suspension of blood cells, and the CTCs are then separated with a magnetic field. This is the basis for Veridex's CellSearch®, the only CTC-enumeration assay cleared by the US Food and Drug Administration (3). The disadvantage of this assay is that it requires multiple processing steps—centrifugation, dilution, capture, separation—and leaves the captured cells nonviable. In microfluidic approaches, whole blood is perfused through channels within which cells collide with antibodies immobilized on the channel walls or obstacles within the …