gebhart/patrepeval huggingface dataset:
Cytokine activation of vascular endothelium. Effects on tissue-type plasminogen activator and type 1 plasminogen activator inhibitor. (1988)

Regulation of the fibrinolytic system of cultured human umbilical vein endothelial cells (HUVECs) by recombinant interleukin 1 beta (rIL-1 beta) and tumor necrosis factor alpha (rTNF alpha) was investigated. Functional and immunologic assays indicated that both cytokines decreased HUVEC tissue-type plasminogen activator (tPA) and increased type 1 plasminogen activator inhibitor (PAI-1) in a dose- and time-dependent manner. Maximal effects (50% decrease in tPA antigen; 300-400% increase in PAI-1 activity) were achieved with 2.5 units/ml rIL-1 beta and 200 units/ml rTNF alpha. Combinations of rIL-1 beta and rTNF alpha were not additive at these maximal concentrations. After a 24-h pretreatment with rIL-1 beta, HUVECs secreted tPA at one-quarter of the rate of control cells and released PAI-1 at a rate that was 5-fold higher than controls. Neither the basal rate of PAI-1 release nor the increased rate of release of PAI-1 in response to rIL-1 beta was affected by subsequently treating the cells with secretagogues (e.g. phorbol myristate acetate) suggesting that PAI-1 is not contained within a rapidly releasable, intracellular storage pool. Northern blot analysis using a PAI-1 cDNA probe indicated that the cytokines increased the steady-state levels of the 3.2- and 2.3-kb PAI-1 mRNA species, but with a preferential increase in the larger mRNA form. The fact that both rIL-1 beta and rTNF alpha act in a similar manner strengthens the hypothesis that the local development of inflammatory/immune processes could reduce endothelial fibrinolytic activity.
Y-Contacted High-Performance n-Type Single-Walled Carbon Nanotube Field-Effect Transistors: Scaling and Comparison with Sc-Contacted Devices (2009)

While it has been shown that scandium (Sc) can be used for making high-quality Ohmic contact to the conduction band of a carbon nanotube (CNT) and thus for fabricating high-performance n-type CNT field effect transistors (FETs), the cost for metal Sc is currently five times more expensive than that for gold and one thousand times more expensive than for yttrium (Y) which in many ways resembles Sc. In this Letter we show that near perfect contacts can be fabricated on single-walled CNTs (SWCNTs) using Y, and the Y-contacted CNT FETs outperform the Sc-contacted CNT FETs in many important aspects. Low-temperature measurements on Y-contacted devices reveal that linear output characteristics persist down to 4.3 K, suggesting that Y makes a perfect Ohmic contact with the conduction band of the CNT. Self-aligned top-gate devices have been fabricated, showing high performance approaching the theoretical limit of CNT-based devices. In particular a room temperature conductance of about 0.55G(0) (with G(0) = 4e(2)/h being the quantum conductance limit of the SWCNT), threshold swing of 73 mV/decade, electron mobility of 5100 cm(2)/V.s, and mean free length of up to 0.639 mum have been achieved. Gate length scaling behavior of the Y-contacted CNT FETs is also investigated, revealing a more favorable energy consumption and faster intrinsic speed scaling than that of the Si-based devices.
Near-infrared spectroscopic measurement of glucose in a protein matrix (1993)

A method is described for measuring clinically relevant levels of glucose in a protein matrix by near-infrared (near-IR) absorption spectroscopy. Results from an initial screening of major blood constituents identify protein as a major potential interference to the near-IR measurement of glucose in blood. The interference by protein is caused by relatively high concentrations coupled with strong near-IR absorption bands between 5000 and 4000 cm-1 (2.0-2.5 microns). Calibration models based on a simple univariate calibration procedure are not capable of providing accurate glucose concentrations from an independent set of prediction spectra. By use of the multivariate technique of partial least squares (PLS) regression, glucose concentrations can be determined with a 0.35 mM (6.3 mg/dL) standard error of prediction. The spectral range for this calibration model extends from 4600 to 4200 cm-1, and the optimum number of PLS factors is 14. In addition, calibration models based on a combination of digital Fourier filtering and PLS regression have been constructed and evaluated. Superior calibration models are obtained by using a preprocessing digital filtering step to remove spectral features not associated with glucose. The best overall calibration model was obtained by using a Gaussian-shaped Fourier filter defined by a mean position of 0.03f and standard deviation of 0.007f coupled with a 12-factor PLS regression computed over the spectral range from 4600 to 4200 cm-1. This model provided a standard error of prediction of 0.24 mM (4.3 mg/dL) for an independent set of prediction spectra.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of interleukin (IL)-3 and IL-5 on human eosinophil degranulation induced by complement components C3a and C5a (1996)

It is suggested that eosinophils (Eos) play an important role in the pathogenesis of bronchial asthma by releasing cytotoxic cationic eosinophil granule proteins and damaging bronchial epithelial cells. However, the exact nature of the actual inducer of eosinophil degranulation in vivo is unclear. We examined eosinophil cationic protein (ECP) release from human Eos in response to soluble agonists such as C5a, C3a, platelet-activating factor, and FMLP with or without interleukin (IL)-3 or IL-5 priming. Eosinophil degranulation induced by these soluble agonists required the pretreatment of Eos by cytochalasin B even in IL-3 priming. Among four agonists, C5a was the most effective stimulus of ECP release either with or without IL-5 priming. IL-3 and IL-5 remarkably enhanced ECP release in Eos triggered by C3a and C5a. The enhancement of ECP release by IL-3 and IL-5 occurred at 0.1–0.3 ng/ml and became maximal at 10–30 ng/ml, concentration-dependently. The enhancement of ECP release by cytokines became optimal at an interval of 10 min. Our data support the importance of complement components and cytokines in eosinophil degranulation in vivo.
Curvilinear Electronics Formed Using Silicon Membrane Circuits and Elastomeric Transfer Elements (2009)

Materials and methods to achieve electronics intimately integrated on the surfaces of substrates with complex, curvilinear shapes are described. The approach exploits silicon membranes in circuit mesh structures that can be deformed in controlled ways using thin, elastomeric films. Experimental and theoretical studies of the micromechanics of such curvilinear electronics demonstrate the underlying concepts. Electrical measurements illustrate the high yields that can be obtained. The results represent significant experimental and theoretical advances over recently reported concepts for creating hemispherical photodetectors in electronic eye cameras and for using printable silicon nanoribbons/membranes in flexible electronics. The results might provide practical routes to the integration of high performance electronics with biological tissues and other systems of interest for new applications.
Thrombopoietin-Induced Differentiation of a Human Megakaryoblastic Leukemia Cell Line, CMK, Involves Transcriptional Activation of p21 WAF1/Cip1 by STAT5 (1997)

Although thrombopoietin (TPO) is known to play a fundamental role in both megakaryopoiesis and thrombopoiesis, the molecular mechanism of TPO-induced megakaryocytic differentiation is not known. In a human megakaryoblastic leukemia cell line, CMK, that showed some degree of megakaryocytic differentiation after culture with TPO, the cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/Cip1), but not p27(Kip1), p16(INK4A), p15(INK4B), or p18(INK4C), was found to be upregulated in an immediately early response to TPO. The expression of p21 was found to be sustained over a period of 5 days by treatment with TPO in large polyploid cells that developed in response to TPO, but not in small undifferentiated cells, indicating a close correlation between the ligand-induced differentiation and p21 induction in CMK cells. To examine potential roles of Cdk inhibitors in megakaryocytic differentiation, CMK cells were transfected with the p21, p27, or p16 gene, together with a marker gene, beta-galactosidase, and were cultured with medium alone for 5 days. The ectopic expression of p21 or p27 but not of p16 led to induction of megakaryocytic differentiation of CMK cells. Overexpression of the N-terminal domain (amino acids [aa] 1 to 75) of p21 was sufficient to induce megakaryocytic differentiation, whereas that of the C-terminal domain (aa 76 to 164) had little or no effect on morphological features. Furthermore, we found that although TPO induced tyrosine phosphorylation of both STAT3 and STAT5 in CMK cells, only STAT5 showed binding activities to potential STAT-binding sites that locate in the promoter region of p21 gene (p21-SIE sites), thereby leading to transactivation of p21. These results suggested that p21 induction, possibly mediated through activated STAT5, could play an important role in TPO-induced megakaryocytic differentiation.
The Effect of Radiation on the Immune Response to Cancers (2014)

In cancer patients undergoing radiation therapy, the beneficial effects of radiation can extend beyond direct cytotoxicity to tumor cells. Delivery of localized radiation to tumors often leads to systemic responses at distant sites, a phenomenon known as the abscopal effect which has been attributed to the induction and enhancement of the endogenous anti-tumor innate and adaptive immune response. The mechanisms surrounding the abscopal effect are diverse and include trafficking of lymphocytes into the tumor microenvironment, enhanced tumor recognition and killing via up-regulation of tumor antigens and antigen presenting machinery and, induction of positive immunomodulatory pathways. Here, we discuss potential mechanisms of radiation-induced enhancement of the anti-tumor response through its effect on the host immune system and explore potential combinational immune-based strategies such as adoptive cellular therapy using ex vivo expanded NK and T cells as a means of delivering a potent effector population in the context of radiation-enhanced anti-tumor immune environment.
Physiological roles of PKB/Akt isoforms in development and disease (2007)

PKB (protein kinase B, also known as Akt) is a serine/threonine protein kinase that is important in various signalling cascades and acts as a major signal transducer downstream of activated phosphoinositide 3-kinase. There are three closely related isoforms of PKB in mammalian cells, PKBalpha (Akt1), PKBbeta (Akt2) and PKBgamma (Akt3), and this review discusses recent advances in our understanding of the functions of these isoforms in the regulation of adipocyte differentiation, glucose homoeostasis and tumour development.
Molecular characterization of human and mouse fatty acid amide hydrolases (1997)

Recently, we reported the isolation, cloning, and expression of a rat enzyme, fatty acid amide hydrolase (FAAH), that degrades bioactive fatty acid amides like oleamide and anandamide to their corresponding acids, thereby serving to terminate the signaling functions of these molecules. Here, we report the molecular characterization of both a mouse and a human FAAH and compare these enzymes to the rat FAAH. The enzymes are well conserved in primary structure, with the mouse and rat FAAHs sharing 91% amino acid identity and the human FAAH sharing 82% and 84% identity with the rat FAAH and mouse FAAH, respectively. In addition, the expressed human and rat FAAHs behave biochemically as membrane proteins of comparable molecular size and show similar, but distinguishable, enzymological properties. The identification of highly homologous FAAH proteins in rat, mouse, and human supports a general role for the fatty acid amides in mammalian biology.
Serotonin Receptor Activation of Phosphoinositide Turnover in Uterine, Fundal, Vascular, and Tracheal Smooth Muscle (1987)

Hydrolysis of phosphatidylinositol is becoming recognized as the second messenger system for a number of hormones and neurotransmitters, including serotonin. The present study was designed to explore the effects of serotonin to enhance phosphoinositide turnover in several smooth muscle preparations, in an effort (a) to determine which smooth muscle preparation might provide a useful system for further study of phosphoinositide turnover and (b) to examine the role of 5-HT2 receptors in such responses. Basal-[3H]inositol monophosphate ([3H]IP) formation was 10-fold higher in the uterus than in the rat jugular vein, aorta, stomach fundus, or guinea pig trachea. Serotonin produced significant elevations in [3H]IP in the rat aorta, uterus, and jugular vein. Maximal elevation in [3H]IP was greatest in the jugular vein (eightfold increase) with an ED50 for serotonin of 0.4 microM. Serotonin (10(-7)-10(-4) M), although a potent contractile agonist in both the guinea pig trachea and rat stomach fundus, did not increase [3H]IP levels in these tissues. The selective 5-HT2 receptor blocker LY53857 (10(-8) M) antagonized the increase in [3H]IP produced by serotonin in the jugular vein, aorta, and uterus. Pargyline (10(-5) M) added to the trachea and fundus did not unmask an effect of serotonin or enhance the response to serotonin in the rat aorta. Thus, the jugular vein was the tissue most sensitive to activation of [3H]IP by serotonin. Increases in [3H]IP produced by serotonin may be linked to activation of 5-HT2 receptors in the jugular vein, aorta, and uterus since the selective 5-HT2 antagonist LY53857 could block this biochemical effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Bench-top fermentative production of plant benzylisoquinoline alkaloids using a bacterial platform (2012)

The plant secondary metabolites benzylisoquinoline alkaloids (BIAs) have diverse pharmaceutical activities, and some are used medicinally (e.g., morphine, codeine, berberine). Recently, we constructed a platform to produce BIAs using bioengineered Escherichia coli, which could be useful for bulk production. The E. coli strain used in this system produces the important intermediate (S)-reticuline from glucose or glycerol. Although the amount produced (40 mg/L) exceeded the amount that can be purified from plants, the conversion efficiency from glycerol was only 0.15%; thus, there was much room for improvement. Our production system was developed in a jar fermenter but it is difficult to work with multiple samples using this system. In contrast, many samples can be cultured in parallel using shake flask cultures, allowing optimization of production conditions. Here, we describe bench-top production of (S)-reticuline and optimization of culture conditions using shake flask cultures. The production of (S)-reticuline reached 33.9 mg/L.
Ischemic Brain Injury is Mediated by the Activation of Poly(ADP-Ribose)Polymerase (1997)

Poly(ADP-ribose)polymerase (PARP, EC 2.4.2.30), an abundant nuclear protein activated by DNA nicks, mediates cell death in vitro by nicotinamide adenine dinucleotide (NAD) depletion after exposure to nitric oxide. The authors examined whether genetic deletion of PARP (PARP null mice) or its pharmacologic inhibition by 3-aminobenzamide (3-AB) attenuates tissue injury after transient cerebral ischemia. Twenty-two hours after reperfusion following 2 hours of filamentous middle cerebral artery occlusion, ischemic injury was decreased in PARP-/- and PARP+/- mice compared with PARP+/+ litter mates, and also was attenuated in 129/SV wild-type mice after 3-AB treatment compared with controls. Infarct sparing was accompanied by functional recovery in PARP-/- and 3-AB-treated mice. Increased poly(ADP-ribose) immunostaining observed in ischemic cell nuclei 5 minutes after reperfusion was reduced by 3-AB treatment. Levels of NAD--the substrate of PARP--were reduced 2 hours after reperfusion and were 35% of contralateral levels at 24 hours. The decreases were attenuated in PARP-/- mice and in 3-AB-treated animals. Poly(ADP-ribose)polymerase cleavage by caspase-3 (CPP-32) has been proposed as an important step in apoptotic cell death. Markers of apoptosis, such as oligonucleosomal DNA damage, total DNA fragmentation, and the density of terminal deoxynucleotidyl transferase dUTP nick-end-labelled (TUNEL +) cells, however, did not differ in ischemic brain tissue of PARP-/- mice or in 3-AB-treated animals versus controls, although there were differences in the number of TUNEL-stained cells reflecting the decrease in infarct size. Thus, ischemic brain injury activates PARP and contributes to cell death most likely by NAD depletion and energy failure, although the authors have not excluded a role for PARP in apoptotic cell death at earlier or later stages in ischemic cell death. Inhibitors of PARP activation could provide a potential therapy in acute stroke.
Plasma enhanced atomic layer deposition of SiNx:H and SiO2 (2011)

As the nanoelectronics industry looks to transition to both three dimensional transistor and interconnect technologies at the &amp;lt;22 nm node, highly conformal dielectric coatings with precise thickness control are increasingly being demanded. Plasma enhanced chemical vapor deposition (PECVD) currently fills this role for most applications requiring low temperature processing but does not always meet step coverage and thickness precision requirements. The authors present results for a hybrid technique, plasma enhanced atomic layer deposition (PEALD), which utilizes typical PECVD process gases and tooling while delivering improved topography coverage and thickness control. Specifically, the authors show that alternating SiH4 gas/N2 plasma exposures applied in an atomic layer deposition sequence can be used to deposit SiNx:H films in a self-limiting fashion with improved conformality and superior performance as a moisture barrier. PEALD of SiO2 using alternating SiH4 and CO2 plasma exposures is further demonstrated.
FBNet: Hardware-Aware Efficient ConvNet Design via Differentiable Neural Architecture Search (2018)

Designing accurate and efficient ConvNets for mobile devices is challenging because the design space is combinatorially large. Due to this, previous neural architecture search (NAS) methods are computationally expensive. ConvNet architecture optimality depends on factors such as input resolution and target devices. However, existing approaches are too expensive for case-by-case redesigns. Also, previous work focuses primarily on reducing FLOPs, but FLOP count does not always reflect actual latency. To address these, we propose a differentiable neural architecture search (DNAS) framework that uses gradient-based methods to optimize ConvNet architectures, avoiding enumerating and training individual architectures separately as in previous methods. FBNets, a family of models discovered by DNAS surpass state-of-the-art models both designed manually and generated automatically. FBNet-B achieves 74.1% top-1 accuracy on ImageNet with 295M FLOPs and 23.1 ms latency on a Samsung S8 phone, 2.4x smaller and 1.5x faster than MobileNetV2-1.3 with similar accuracy. Despite higher accuracy and lower latency than MnasNet, we estimate FBNet-B's search cost is 420x smaller than MnasNet's, at only 216 GPU-hours. Searched for different resolutions and channel sizes, FBNets achieve 1.5% to 6.4% higher accuracy than MobileNetV2. The smallest FBNet achieves 50.2% accuracy and 2.9 ms latency (345 frames per second) on a Samsung S8. Over a Samsung-optimized FBNet, the iPhone-X-optimized model achieves a 1.4x speedup on an iPhone X.
Antitumor Agents 155. Synthesis and Biological Evaluation of 3',6,7-Substituted 2-Phenyl-4-quinolones as Antimicrotubule Agents (1994)

A series of 3',6,7-substituted 2-phenyl-4-quinolones were designed and synthesized as antimitotic antitumor agents. All compounds showed cytotoxic effects (log GI50 < or = -4.0; log drug molar concentration required to cause 50% inhibition) against the growth of a variety of human tumor cell lines, including those derived from solid tumors such as non-small cell lung, colon, central nervous system, ovary, prostate, and breast cancers, when evaluated in the National Cancer Institute's 60 human tumor cell line in vitro screen. The most potent compound (26) demonstrated strong cytotoxic effects with GI50 values in the nanomolar or subnanomolar range in almost all the tumor cell lines. Compound 26 was also a potent inhibitor of tubulin polymerization and radiolabeled colchicine binding to tubulin, with activity comparable to those of the potent antimitotic natural products colchicine, podophyllotoxin, and combretastatin A-4.
Simplified Reaction Mechanisms for the Oxidation of Hydrocarbon Fuels in Flames (1981)

Abstract Simplified reaction mechanisms for the oxidation of hydrocarbon fuels have been examined using a numerical laminar flame model. The types of mechanisms studied include one and two global reaction steps as well as quasi-global mechanisms. Reaction rate parameters were varied in order to provide the best agreement between computed and experimentally observed flame speeds in selected mixtures of fuel and air. The influences of the various reaction rate parameters on the laminar flame properties have been identified, and a simple procedure to determine the best values for the reaction rate parameters is demonstrated. Fuels studied include n-paraffins from methane to n-decane, some methyl-substituted n-paraffins, acetylene, and representative olefin, alcohol and aromatic hydrocarbons. Results show that the often-employed choice of simultaneous first order fuel and oxidizer dependence for global rate expressions cannot yield the correct dependence of flame speed on equivalence ratio or pressure and cannot correctly predict the rich flammability limit. However, the best choice of rate parameters suitably reproduces rich and lean flammability limits as well as the dependence of the flame speed on pressure and equivalence ratio for all of the fuels examined. Two-step and quasi-global approaches also yield information on flame temperature and burned gas composition. However, none of the simplified mechanisms studied accurately describes the chemical structure of the flame itself.
The DNA sequence of the mercury resistance operon of the IncFII plasmid NR1. (1984)

The DNA sequence has been determined for a 3.8-kilobase region which encodes the mercury resistance (mer) operon of the IncFII plasmid NR1. The sequence reveals four open reading frames which could encode proteins of 12,391, 9,429, 14,965, and 58,781 daltons. On the basis of their sizes, amino acid compositions, hydropathicities, and estimated isoelectric points, the peptides encoded by these open reading frames correspond to the four previously described Hg-inducible proteins detected in minicells carrying mer+ plasmids. The NR1 mer locus is 63.4% GC overall, and the Hg(II) reductase protein sequence is 90% homologous to that of Tn501. The region encoding the merR (positive regulatory) function has three open reading frames. The smallest of these possible merR peptides (6,457 daltons) begins approximately 280 bp to the right of the adjacent IS1b and reads towards the structural genes of the mer operon. The next largest reading frame (13,139 daltons) in the merR region begins 37 bp to the left of the beginning of the smallest peptide and also reads towards the structural genes. The largest reading frame (15,907 daltons) in the merR region lies on the complementary strand and reads away from the structural genes towards IS1b. Although attempts to visualize the merR gene product were not successful, in vitro mutagenesis allows us to eliminate the largest reading frame as a merR candidate. We were also able to show that approximately 50% of the smallest detectable mer peptide (9,429 daltons) is located in the periplasm.