gebhart/patrepeval huggingface dataset:
Copper induces apoptosis in BA/F3? cells: Bax, reactive oxygen species, and NF?B are involved (2000)

Copper, an essential trace element, can be toxic to some cells when present in excess. But thorough investigations into the cytotoxicity of copper and subsequent molecular mechanisms are rare, although the cytotoxicity of copper has been applied to cancer chemotherapy. The present study demonstrates that Cu(2+) inhibits [(3)H] thymidine incorporation in mouse pro-B cell line BA/F3beta and induces apoptosis. Apoptosis was mainly judged by morphology of cells, quantification of subdiploid DNA contents by flow cytometry, and detection of DNA fragmentation by gel electrophoresis. The apoptotic effect is dose and time dependent. Western blotting shows Bax is upregulated by Cu(2+). Bcl-2 overexpression can partially inhibit this apoptosis. Moreover, Cu(2+) increases the production of reactive oxygen species (ROS) in a dose-dependent manner. The antioxidant N-acetylcysteine (NAC) not only significantly inhibited copper-induced apoptosis but also totally blocked generation of ROS, while Bcl-2 overexpression has no effect on the generation of ROS. Furthermore, our results show that NFkappaB is downregulated by Cu(2+). Bcl-2 overexpression or NAC can sustain the activity of NFkappaB. These data indicate that Cu(2+) might induce apoptosis in BA/F3beta cells via upregulation of Bax and ROS and subsequent inactivation of NFkappaB.
Four genes, two ends, and a <i>res</i> region are involved in transposition of Tn<i>5053</i>: a paradigm for a novel family of transposons carrying either a <i>mer</i> operon or an integron (1995)

The complete nucleotide sequence of an 8447 bp-long mercury-resistance transposon (Tn5053) has been determined. Tn5053 is composed of two modules: (i) the mercury-resistance module and (ii) the transposition module. The mercury-resistance module carries a mer operon, merRTPFAD, and appears to be a single-ended relic of a transposon closely related to the classical mercury-resistance transposons Tn21 and Tn501. The transposition module of Tn5053 is bounded by 25 bp terminal inverted repeats and contains four genes involved in transposition, i.e. tniA, tniB, tniQ, and tniR. Transposition of Tn5053 occurs via cointegrate formation mediated by the products of the tniABQ genes, followed by site-specific cointegrate resolution. This is catalysed by the product of the tniR gene at the res region, which is located upstream of tniR. The same pathway of transposition is used by Tn402 (Tn5090) which carries the integron of R751. Transposition genes of Tn5053 and Tn402 are interchangeable. Sequence analysis suggests that Tn5053 and Tn402 are representatives of a new family of transposable elements, which fall into a recently recognized super-family of transposons including retroviruses, insertion sequences of the IS3 family, and transposons Tn552 and Tn7. We suggest that the tni genes were involved in the dissemination of integrons.
Estimation of metals in solution by means of their spark spectra (1931)

Abstract This paper records experiments undertaken to extend to liquids the accuracy of quantitative analysis recently attained by the spectrography of alloys. How to produce from a solution a spectrum which shall truly represent the solution, and what effect may be expected from the presence of other metals than the one under determination, are among the questions dealt with, for they must come into consideration in applying any method of quantitative spectrography of solutions. The Production of the Spark. (a) The Sparking Vessel for Liquids.—At the outset of the investigation it became apparent that the older forms of sparking apparatus, used by Hartley, Pollok and Leonard, and others, were unsuitable for quantitative work, for it was found that, owing to incrustation of the electrodes and to decomposition of the solution around them, the spark soon became unrepresentative of the bulk of the solution.
A Two-Way Interleaved 7-b 2.4-GS/s 1-Then-2 b/Cycle SAR ADC With Background Offset Calibration (2018)

This paper presents a 2× time-interleaved 7-b 2.4-GS/s 1-then-2 b/cycle SAR ADC in 28-nm CMOS. The process-voltage-temperature sensitivity of a multi-bit SAR architecture has been improved by the proposed 1-then-2 b/cycle scheme with background offset calibration. With the pre-charge reduction scheme, the traditional large switching energy and time consuming pre-charge operation have been removed, which simultaneously enables a simple control logic without the need of a V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">cm</sub> voltage. Besides, a background offset calibration is implemented on chip which does not involve any extra phase or calibration input signal. Its operation is well embedded within the 1-then-2 b/cycle architecture, thus leading to a very minimal modification of the ADC core. With an improved fringing DAC structure and a high-speed dynamic logic circuit, a single-channel ADC can work at 1.2 GS/s under a 0.9-V supply. Using two-way time interleaving, the prototype samples at 2.4 GHz and consumes 5-mW power including the on-chip background offset calibration. It exhibits a 40.05-dB SNDR at Nyquist, leading to a Walden FoM of 25.3 fJ/conversion step. Measurement results show that the SNDR of the ADC can be kept above 38 dB at 2 GS/s under a wide range of temperature, supply, and input common-mode variation.
HSV-1 as a Model for Emerging Gene Delivery Vehicles (2013)

The majority of viral vectors currently used possess modest cargo capability (up to 40 kb) being based on retroviruses, lentiviruses, adenoviruses, and adenoassociated viruses. These vectors have made the most rapid transition from laboratory to clinic because their small genomes have simplified their characterization and modification. However, there is now an increasing need both in research and therapy to complement this repertoire with larger capacity vectors able to deliver multiple transgenes or to encode complex regulatory regions, constructs which can easily span more than 100 kb. Herpes Simplex Virus Type I (HSV-1) is a well-characterized human virus which is able to package about 150 kb of DNA, and several vector systems are currently in development for gene transfer applications, particularly in neurons where other systems have low efficiency. However, to reach the same level of versatility and ease of use as that of smaller genome viral vectors, simple systems for high-titer production must be developed. This paper reviews the major HSV-1 vector systems and analyses the common elements which may be most important to manipulate to achieve this goal.
A new paradigm for synthesis and propagation of clock gating conditions (2008)

Clock gating has become a standard practice for saving dynamic power in the clock network. Due to design reuse, it is common to find designs that have already some partial clock gating. We propose to exploit the existing clock gating in order to extract stronger gating conditions for blocks that are poorly gated or not gated at all. A second contribution of our paper is a robust and scalable approach to extract stability conditions for clock gating. Finally, we present a uniform treatment of unobservability and stability as dual approaches for propagating gating conditions forward and backward. Experimental results demonstrate significant power reduction (in the range of 14% -- 55% of the clock power) on Intel micro-processor designs.
CD4(+) T cells tolerized ex vivo to host alloantigen by anti-CD40 ligand (CD40L:CD154) antibody lose their graft-versus-host disease lethality capacity but retain nominal antigen responses. (1998)

A major goal of the transplant field is to tolerize donor T cells to prevent graft-versus-host disease (GVHD) (1). We describe an ex vivo approach in which the blockade of CD40 ligand (CD40L:CD154):CD40 interactions, a pathway required for optimal T cell expansion, induces donor CD4(+) T cells to become tolerant to host alloantigens (2). High doses of tolerized cells did not cause GVHD lethality in vivo. T cells had intact responses to antigens not present during tolerization. Tolerance was long lived and not readily reversible in vivo. These data have significant implications for the use of tolerization approaches to prevent human GVHD.
Coupling of neuronal 5‐HT<sub>7</sub> receptors to activation of extracellular‐regulated kinase through a protein kinase A‐independent pathway that can utilize Epac (2003)

The roles of 3',5'-cyclic adenosine monophosphate (cAMP) and protein kinase A in 5-hydroxytryptamine (5-HT)7 receptor-mediated activation of extracellular-regulated kinase (ERK) were studied in cultured hippocampal neurons and transfected PC12 cells. Activation of ERK by neuronal Gs-coupled receptors has been thought to proceed through a protein kinase A-dependent pathway. In fact we identified coupling of 5-HT7 receptors to activation of adenylyl cyclase and protein kinase A. However, no inhibition of agonist-stimulated ERK activation was found when cells were treated with H-89 and KT5720 at concentrations sufficient to completely inhibit activation of protein kinase A. However, activation of ERK was found to be sensitive to the adenylyl cyclase inhibitor 9-(tetrahydrofuryl)-adenine, suggesting a possible role for a cAMP-guanine nucleotide exchange factor (cAMP-GEF). Co-treatment of cells with 8-(4-chlorophenylthio)-2'-O-methyladenosine 3',5'-cyclic monophosphate, a direct activator of the cAMP-GEFs Epac1 and 2, reversed the inhibition of agonist-stimulated ERK activation induced by adenylyl cyclase inhibition. Additionally, over-expression of Epac1 enhanced 5-HT7 receptor-mediated activation of ERK. These results demonstrate that the activation of ERK mediated by neuronal Gs-coupled receptors can proceed through cAMP-dependent pathways that utilize cAMP-GEFs rather than protein kinase A.
Prostacyclin Synthase Gene Transfer Accelerates Reendothelialization and Inhibits Neointimal Formation in Rat Carotid Arteries After Balloon Injury (1999)

Prostacyclin (PGI2), a metabolite of arachidonic acid, has the vasoprotective effects of vasodilation, anti-platelet aggregation, and inhibition of smooth muscle cell proliferation. We hypothesized that an overexpression of endogenous PGI2 may accelerate the recovery from endothelial damage and inhibit neointimal formation in the injured artery. To test this hypothesis, we investigated in vivo transfer of the PGI2 synthase (PCS) gene into balloon-injured rat carotid arteries by a nonviral lipotransfection method. Seven days after transfection, a significant regeneration of endothelium was observed in the arteries transfected with a plasmid carrying the rat PCS gene (pCMV-PCS), but little regeneration was seen in those with the control plasmid carrying the lacZ gene (pCMV-lacZ) (percent luminal circumference lined by newly regenerated endothelium: 87. 1+/-6.9% in pCMV-PCS-transfected vessels and 6.9+/-0.2% in pCMV-lacZ vessels, P<0.001). BrdU staining of arterial segments demonstrated a significantly lower incorporation in pCMV-PCS-transfected vessels (7. 5+/-0.3% positive nuclei in vessel cells) than in pCMV-lacZ (50. 7+/-9.6%, P<0.01). Moreover, 2 weeks after transfection, the PCS gene transfer resulted in a significant inhibition of neointimal formation (88% reduction in ratio of intima/media areas), whereas medial area was similar among the groups. Arterial segments transfected with pCMV-PCS produced significantly higher levels of 6-keto-PGF1alpha, the main metabolite of PGI2, compared with the segments transfected with pCMV-lacZ (10.2+/-0.55 and 2.1+/-0.32 ng/mg tissue for pCMV-PCS and pCMV-placZ, P<0.001). In conclusion, this study demonstrated that an in vivo PCS gene transfer increased the production of PGI2 and markedly inhibited neointimal formation with accelerated reendothelialization in rat carotid arteries after balloon injury.
Polarization Resistance Method for Determination of Instantaneous Corrosion Rates (2000)

The polarization resistance method for the determination of instantaneous corrosion rates of metals were reviewed. The assumptions in electrode kinetics that govern the connection between the slope of steady-state applied electrochemical potential-applied current density (Eapp-iapp) measurements (i.e., the polarization resistance) and the corrosion rate were restated. Electrochemical impedance, as well as statistical and spectral electrochemical noise methods for obtaining polarization resistance, also were discussed. Traditional sources of error such as high excitation voltage amplitudes, insufficiently slow voltage ramp rates, high alternating current (AC) frequencies, inadequate polarization hold periods, high solution resistance, presence of parallel reduction-oxidation reactions, and nonuniform current and potential distributions were examined with the goal of defining some of the conditions and circumstances where these complicating factors are important. Other complicating factors such as diffusion-controlled reactions, potential-dependent film coverages, and adsorption pseudo-capacitance that affect electrochemical reaction rates were discussed. Their influence on measured interfacial resistance values and subsequent determination of corrosion rates was discussed.
A Lipopolysaccharide from Pantoea Agglomerans Is a Promising Adjuvant for Sublingual Vaccines to Induce Systemic and Mucosal Immune Responses in Mice via TLR4 Pathway (2015)

A lipopolysaccharide from Pantoea agglomerans (LPSpa) has been applied to various fields for human use as a Toll-like receptor 4 ligand and its safety has been confirmed. Here, we showed for the first time the application of LPSpa as an effective mucosal adjuvant for activating vaccine-induced antigen specific immune responses. Mice sublingually immunized with influenza vaccine (HA split vaccine) with LPSpa induced both HA-specific IgG (systemic) and IgA (mucosal) antibody responses, which led to a significant increase in survival rate against lethal influenza virus challenge compared with subcutaneous vaccination. After sublingual administration of ovalbumin with LPSpa, ovalbumin-specific mucosal IgA responses were induced at both mucosal surfaces close to the immunized site and at remote mucosal surfaces. Sublingual administration of LPSpa evoked local antigen-uptake by dendritic cells in cervical lymph nodes. LPSpa induced cytokine production and the maturation and proliferation of innate immune cells via Toll-like receptor 4 in dendritic cells. Collectively, these results suggest that LPSpa can be used as an effective mucosal adjuvant to stimulate and activate local innate immune cells to improve and enhance mucosal vaccine potency against various pathogens.
THE ROLE OF SOCIAL SUPPORT AND FAMILY RELATIONSHIPS IN WOMEN'S RESPONSES TO BATTERING (2000)

For women who are in abusive relationships, social support and close family relationships may be critical to the successful resolution of the abuse. Efforts to enhance battered women's support must be predicated on an understanding of women's perceptions of effective support and the constraints they experience to seeking support. In this paper we present findings from a qualitative analysis of semistructured interviews with 31 women who were in abusive relationships. The women were interviewed three times over two-and-a-half years. Results of the analysis included that women used female friends for support more often than family members, and that women were constrained from seeking support by (a) cultural and societal sanctions against leaving the relationship; (b) a pattern of caution in relating to others or forging new relationships; and (c) forced isolation/seeing self as isolative. Relationships with family members, especially parents, were not consistently seen as useful sources of support.
THE ENHANCEMENT OF ENDOGENOUS cAMP WITH PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE PROTECTS RAT KIDNEY AGAINST ISCHEMIA THROUGH THE MODULATION OF INFLAMMATORY RESPONSE12 (2001)

Enhancement of endogenous circulating cAMP with PACAP-38 modulates postischemic inflammatory response and strongly protects from ischemic acute renal failure, even when administration is delayed for 6 hr after injury.
The Bacterial Defensin Resistance Protein MprF Consists of Separable Domains for Lipid Lysinylation and Antimicrobial Peptide Repulsion (2009)

Many bacterial pathogens achieve resistance to defensin-like cationic antimicrobial peptides (CAMPs) by the multiple peptide resistance factor (MprF) protein. MprF plays a crucial role in Staphylococcus aureus virulence and it is involved in resistance to the CAMP-like antibiotic daptomycin. MprF is a large membrane protein that modifies the anionic phospholipid phosphatidylglycerol with l-lysine, thereby diminishing the bacterial affinity for CAMPs. Its widespread occurrence recommends MprF as a target for novel antimicrobials, although the mode of action of MprF has remained incompletely understood. We demonstrate that the hydrophilic C-terminal domain and six of the fourteen proposed trans-membrane segments of MprF are sufficient for full-level lysyl-phosphatidylglycerol (Lys-PG) production and that several conserved amino acid positions in MprF are indispensable for Lys-PG production. Notably, Lys-PG production did not lead to efficient CAMP resistance and most of the Lys-PG remained in the inner leaflet of the cytoplasmic membrane when the large N-terminal hydrophobic domain of MprF was absent, indicating a crucial role of this protein part. The N-terminal domain alone did not confer CAMP resistance or repulsion of the cationic test protein cytochrome c. However, when the N-terminal domain was coexpressed with the Lys-PG synthase domain either in one protein or as two separate proteins, full-level CAMP resistance was achieved. Moreover, only coexpression of the two domains led to efficient Lys-PG translocation to the outer leaflet of the membrane and to full-level cytochrome c repulsion, indicating that the N-terminal domain facilitates the flipping of Lys-PG. Thus, MprF represents a new class of lipid-biosynthetic enzymes with two separable functional domains that synthesize Lys-PG and facilitate Lys-PG translocation. Our study unravels crucial details on the molecular basis of an important bacterial immune evasion mechanism and it may help to employ MprF as a target for new anti-virulence drugs.
Sensor Planning for Mobile Robot Localization Using Structure Learning and Inference of Bayesian Network (2004)

In this paper we propose a novel method of sensor planning for a mobile robot localization problem. We represent causal relation between local sensing results, actions, and belief of the global localization using a Bayesian network. Initially, the structure of the Bayesian network is learned from the complete data of the environment using K2 algorithm combined with GA (genetic algorithm) . In the execution phase, when the robot is kidnapped to some place, it plans an optimal sensing action by taking into account the trade-off between the sensing cost and the global localization belief which is obtained by inference in the Bayesian network. We have validated the learning and planning algorithm by simulation experiments in an office environment.
Object oriented circuit-generators in Java (2002)

Generators, parameterized code which produces a digital design, have long been a staple of the VLSI community. In recent years, several field programmable gate array (FPGA) design tools have adopted generators, as it is a convenient way to specify reusable designs in a familiar programming environment. We have built a generator framework in Java as a basis for programming reconfigurable devices and as a tool to be embedded in larger development systems. In addition to the conventional benefits of generators, this powerful framework allows for partial evaluation, simulation, specialization, and easy inclusion of other automatic services. In order to verify the utility of this system, we have implemented several applications using this framework and compared them with implementations using schematic capture and HDL synthesis. Our system runs significantly faster and produces comparable or superior results when mapped to a target FPGA.
Integrating Simulations and Experiments To Predict Sheet Resistance and Optical Transmittance in Nanowire Films for Transparent Conductors (2013)

Metal nanowire films are among the most promising alternatives for next-generation flexible, solution-processed transparent conductors. Breakthroughs in nanowire synthesis and processing have reported low sheet resistance (Rs ≤ 100 Ω/sq) and high optical transparency (%T > 90%). Comparing the merits of the various nanowires and fabrication methods is inexact, because Rs and %T depend on a variety of independent parameters including nanowire length, nanowire diameter, areal density of the nanowires and contact resistance between nanowires. In an effort to account for these fundamental parameters of nanowire thin films, this paper integrates simulations and experimental results to build a quantitatively predictive model. First, by fitting the results from simulations of quasi-2D rod networks to experimental data from well-defined nanowire films, we obtain an effective average contact resistance, which is indicative of the nanowire chemistry and processing methods. Second, this effective contact resistance is used to simulate how the sheet resistance depends on the aspect ratio (L/D) and areal density of monodisperse rods, as well as the effect of mixtures of short and long nanowires on the sheet resistance. Third, by combining our simulations of sheet resistance and an empirical diameter-dependent expression for the optical transmittance, we produced a fully calculated plot of optical transmittance versus sheet resistance. Our predictions for silver nanowires are validated by experimental results for silver nanowire films, where nanowires of L/D > 400 are required for high performance transparent conductors. In contrast to a widely used approach that employs a single percolative figure of merit, our method integrates simulation and experimental results to enable researchers to independently explore the importance of contact resistance between nanowires, as well as nanowire area fraction and arbitrary distributions in nanowire sizes. To become competitive, metal nanowire systems require a predictive tool to accelerate their design and adoption for specific applications.
Stereospecific Synthesis, Structure−Activity Relationship, and Oral Bioavailability of Tetrahydropyrimidin-2-one HIV Protease Inhibitors (1998)

The use of tetrahydropyrimidinones as an alternate scaffold for designing HIVPR inhibitors has advantages, over the previously disclosed hexahydro-1,3-diazepin-2-ones, of being more unsymmetrical (different P1/P1'), less crystalline, more soluble, and more lipophilic (mono-ol vs diol). They show a better translation of Ki to IC90 for the more polar P2 groups that in general give the more potent enzyme inhibitors. Structure-activity relationship (SAR) studies of the tetrahydropyrimidinones showed that the phenylethyl P1' substituent, the hydroxyl group, and the urea carbonyl are all critical for good activity. However, there was significant flexibility in the possible P2/P2' substituents that could be used. Many analogues that contained identical or different P2/P2' substituents, or only one P2 substituent, were found to have excellent enzyme potency and several had excellent antiviral potency. Several of these compounds were examined for oral bioavailability in the rat or the dog at 10 mg/kg. However, the oral bioavailability of the tetrahydropyrimidinones was, in general, less than the corresponding hexahydro-1,3-diazepin-2-ones. Unfortunately, when all factors are considered, including potency, protein binding, solubility, bioavailability, and resistance profile, the tetrahydropyrimidinones did not offer any advantage over the previously disclosed hexahydro-1,3-diazepin-2-ones series.
Silk/agarose scaffolds with tunable properties via SDS assisted rapid gelation (2017)

We developed a simple approach to fabricate silk/agarose scaffolds with tunable properties <italic>via</italic> controlling the gelation degree of silk fibroin.