gebhart/patrepeval huggingface dataset:
Expression of Constitutively Active Phosphatidylinositol 3-Kinase Inhibits Activation of Caspase 3 and Apoptosis of Cardiac Muscle Cells (2000)

Apoptosis of cardiac muscle cells contributes to the development of cardiomyopathy. Recent studies showed that insulin-like growth factor I (IGF-I) inhibits apoptosis of cardiac muscle cells and improves myocardial function in experimental heart failure. This study was carried out to elucidate the role of phosphatidylinositol 3-kinase (PI 3-kinase) in the anti-apoptotic actions of IGF-I in cardiomyocytes and to explore whether expression of constitutively active PI 3-kinase can inhibit apoptosis in cardiomyocytes. Apoptosis of primary cardiomyocytes was induced by doxorubicin treatment and serum withdrawal. Transduction of cardiomyocytes with constitutively active PI 3-kinase specifically lead to serine phosphorylation of Akt, whereas phosphorylation of IGF-I receptor, IRS1/2 and p44/42 mitogen-activated protein kinase were not increased. In the cardiomyocytes transduced with constitutively active PI 3-kinase, activation of the pro-apoptotic caspase 3 was attenuated and fragmentation of DNA was reduced. Preincubating cells with PI 3-kinase inhibitor LY294002 was associated with loss of anti-apoptotic actions of IGF-I and PI 3-kinase. Neither IGF-I nor constitutively active PI 3-kinase lead to serine phosphorylation of Bad, suggesting that the anti-apoptotic effects of PI 3-kinase are not mediated through Bad phosphorylation in cardiac muscle cells. To determine whether activation of caspase 3 is sufficient to induce apoptosis in cardiomyocytes, an engineered TAT-caspase 3 protein was introduced to cardiomyocytes. Significant reduction of cell viability occurred in the cardiomyocytes transduced with active caspase 3, indicating that activation of caspase 3 is sufficient to cause cardiomyocyte death. These findings indicate the existence of an IGF-I receptor-PI 3-kinase-caspase 3 pathway in cardiomyocytes that plays an important role in the anti-apoptotic actions of IGF-I in heart. Moreover, these data suggest that modulation of PI 3-kinase activities may represent a potential therapeutic strategy to counteract the occurrence of apoptosis in cardiomyopathy.
Energetics of the HIV gp120-CD4 binding reaction (2000)

HIV infection is initiated by the selective interaction between the cellular receptor CD4 and gp120, the external envelope glycoprotein of the virus. We used analytical ultracentrifugation, titration calorimetry, and surface plasmon resonance biosensor analysis to characterize the assembly state, thermodynamics, and kinetics of the CD4-gp120 interaction. The binding thermodynamics were of unexpected magnitude; changes in enthalpy, entropy, and heat capacity greatly exceeded those described for typical protein-protein interactions. These unusual thermodynamic properties were observed with both intact gp120 and a deglycosylated and truncated form of gp120 protein that lacked hypervariable loops V1, V2, and V3 and segments of its N and C termini. Together with previous crystallographic studies, the large changes in heat capacity and entropy reveal that extensive structural rearrangements occur within the core of gp120 upon CD4 binding. CD spectral studies and slow kinetics of binding support this conclusion. These results indicate considerable conformational flexibility within gp120, which may relate to viral mechanisms for triggering infection and disguising conserved receptor-binding sites from the immune system.
Redox Regulation of RhoA (2006)

We have previously shown that redox agents including superoxide anion radical and nitrogen dioxide can react with GXXXXGK(S/T)C motif-containing GTPases (i.e., Rac1, Cdc42, and RhoA) to stimulate guanine nucleotide release. We now show that the reaction of RhoA with redox agents leads to different functional consequences from that of Rac1 and Cdc42 due to the presence of an additional cysteine (GXXXCGK(S/T)C) in the RhoA redox-active motif. While reaction of redox agents with RhoA stimulates guanine nucleotide dissociation, RhoA is subsequently inactivated through formation of an intramolecular disulfide that prevents guanine nucleotide binding thereby causing RhoA inactivation. Thus, redox agents may function to downregulate RhoA activity under conditions that stimulate Rac1 and Cdc42 activity. The opposing functions of these GTPases may be due in part to their differential redox regulation. In addition, the results presented herein suggest that the platinated-chemotherapeutic agent, cisplatin, which is known for targeting nucleic acids, reacts with RhoA to produce a RhoA thiol-cisplatin-thiol adduct, leading to inactivation of RhoA. Similarly, certain arsenic complexes (i.e., arsenate and arsenic trioxide) may inactivate RhoA by bridging the cysteine residues in the GXXXCGK(S/T)C motif. Thus, in addition to redox agents, platinated-chemotherapeutic agents and arsenic complexes may modulate the activity of GTPases containing the GXXXCGK(S/T)C motif (i.e., RhoA and RhoB).
From amplified spontaneous emission to microring lasing using nanocrystal quantum dot solids (2002)

We study different emission regimes in close-packed films of chemically synthesized CdSe nanoparticles [nanocrystal quantum dots (NQDs)]. We observe that the NQD photoluminescence is dominated by excitons and biexcitons, respectively, before and after the threshold for stimulated emission. Furthermore, we demonstrate the regime of microring lasing into sharp, whispering-gallery modes using NQD solids incorporated into microcapillary tubes. This result indicates a feasibility of miniature, solid-state laser devices based on chemically synthesized NQDs.
Mice lacking the EDB segment of fibronectin develop normally but exhibit reduced cell growth and fibronectin matrix assembly in vitro. (2002)

Fibronectins (FNs) are major cell-adhesive proteins in the extracellular matrix and are essential for embryonic development. FNs are encoded by a single gene, but heterogeneity is introduced by alternative pre-mRNA splicing. One of the alternatively spliced segments, extra domain B (EDB), is prominently expressed during embryonic development and in tumor tissues, although it is mostly eliminated from FN in normal adult tissues. To examine the function of the EDB segment in vivo, we generated mice lacking the EDB exon using the Cre-loxP system. Although EDB-containing FNs are highly expressed throughout early embryogenesis, EDB-deficient mice developed normally and were fertile. Despite the absence of any significant phenotypes observed in vivo, however, fibroblasts obtained from EDB-deficient mice grew slowly in vitro and deposited less FN in the pericellular matrix than fibroblasts from wild-type mice. These results indicate that expression of EDB-containing isoforms is dispensable during embryonic development, yet may play a modulating role in the growth of connective tissue cells via the FN matrix.
Convexification of AC optimal power flow (2014)

This overview paper summarizes the key elements of semidefinite relaxations of the optimal power flow problem, and discusses several open challenges.
Presence of Permanently Activated Signal Transducers and Activators of Transcription in Nuclear Interchromatin Granules of Unstimulated Mouse Oocytes and Preimplantation Embryos1 (2004)

We previously described that mouse oocytes and preimplantation embryos express the two subunits of interferon-gamma receptor. We now report that, despite the presence of STAT1 (signal transducer and activator of transcription 1) at both the mRNA and protein levels, interferon gamma (IFNgamma) as well as IFNalpha are unable to trigger massive nuclear translocation of STAT1 in these cells, even at high cytokine concentrations. Conversely, nuclear accumulation of STAT1 was readily observed in murine L929 somatic cells under the same conditions. However, in the absence of any stimulation, both tyrosine (Y701p) and serine (S727p) phosphorylated forms of STAT1 were already detected in the nuclei of oocytes and early embryos. Phosphorylated STAT1 appeared concentrated in large nuclear dots, which were identified by indirect immunofluorescence and electron microscopy as clusters of interchromatin granules (IGCs or speckles). A similar distribution was also observed for the serine (S727p) phosphorylated form of STAT3 as well as for tyrosine (Y689p) phosphorylated STAT2. Western blot analysis confirmed that STAT factors present in mouse oocytes are predominantly phosphorylated. In parallel, we showed that the transcription of two IFNgamma-target genes, namely interferon regulatory factor-1 (IRF-1) and suppressor of cytokine signaling-1 (SOCS-1) is indeed increased in two-cell embryos in response to IFNgamma. Altogether, our results suggest that, despite the lack of massive nuclear accumulation of STAT1 in response to exogenous IFNs and the permanent presence of phosphorylated STATs in the nucleus, JAK/ STAT pathways are functional during early development.
Phase-stabilized two-dimensional electronic spectroscopy (2004)

Two-dimensional (2D) spectroscopy is a powerful technique to study nuclear and electronic correlations between different transitions or initial and final states. Here we describe in detail our development of inherently phase-stabilized 2D Fourier-transform spectroscopy for electronic transitions. A diffractive-optic setup is used to realize heterodyne-detected femtosecond four-wave mixing in a phase-matched box geometry. Wavelength tunability in the visible range is accomplished by means of a 3 kHz repetition-rate laser system and optical parametric amplification. Nonlinear signals are fully characterized by spectral interferometry. Starting from fundamental principles, we discuss the origin of phase stability and the precise calibration of excitation-pulse time delays using movable glass wedges. Automated subtraction of undesired scattering terms removes experimental artifacts. On the theoretical side, the response-function formalism is extended to describe molecules with three electronic levels, and the shape of 2D spectral features is discussed. As an example for this technique, experimental 2D spectra are shown for the dye molecule Nile Blue in acetonitrile at 595 nm, recorded for a series of population times. Simulations explore the influence of different model parameters and qualitatively reproduce the experimental results. We show that correlations between different electronically excited states can be determined from the spectra. The technique described here can be used to measure the third-order response function of complex systems covering several electronic transitions.
Expression of tetanus toxin fragment C inE.coli: high level expression by removing rare codons (1989)

Tetanus toxin fragment C had been previously expressed in Escherichia coli at 3-4% cell protein. The codon bias for tetanus toxin in Clostridium tetani is very different from that of highly expressed homologous genes in E. coli, resulting in the presence of many rare E. coli codons in the sequence encoding fragment C. We have replaced the coding sequence by sequence optimized for codon usage in E. coli, and show that the expression of fragment C is increased. Although the level of mRNA also increased this appeared to be a secondary consequence of more efficient translation. Complete sequence replacement increased expression to approximately 11-14% cell protein but only after the promoter strength had been improved.
Steiner tree optimization for buffers, blockages, and bays (2001)

Timing optimization is a critical component of deep submicrometer design and buffer insertion is an essential technique for achieving timing closure. This work studies buffer insertion under the constraint that the buffers either: (1) avoid blockages or (2) are contained within preassigned buffer bay regions. We propose a general Steiner-tree formulation to drive this application and present a maze-routing-based heuristic that either avoids blockages or finds buffer bays. We show that the combination of our Steiner-tree optimization with leading-edge buffer-insertion techniques leads to effective solutions on industry designs.
Psychedelics, Personality and Political Perspectives (2017)

The psychedelic experience (including psychedelic-induced ego dissolution) can effect lasting change in a person's attitudes and beliefs. Here, we aimed to investigate the association between naturalistic psychedelic use and personality, political perspectives, and nature relatedness using an anonymous internet survey. Participants (N = 893) provided information about their naturalistic psychedelic, cocaine, and alcohol use, and answered questions relating to personality traits of openness and conscientiousness (Ten-Item Personality Inventory), nature relatedness (Nature-Relatedness Scale), and political attitudes (one-item liberalism-conservatism measure and five-item libertarian-authoritarian measure). Participants also rated the degree of ego dissolution experienced during their "most intense" recalled psychedelic experience (Ego-Dissolution Inventory). Multivariate linear regression analysis indicated that lifetime psychedelic use (but not lifetime cocaine use or weekly alcohol consumption) positively predicted liberal political views, openness and nature relatedness, and negatively predicted authoritarian political views, after accounting for potential confounding variables. Ego dissolution experienced during a participant's "most intense" psychedelic experience positively predicted liberal political views, openness and nature relatedness, and negatively predicted authoritarian political views. Further work is needed to investigate the nature of the relationship between the peak psychedelic experience and openness to new experiences, egalitarian political views, and concern for the environment.
A major continuous allergenic epitope of bovine β‐lactoglobulin recognized by human IgE binding (1994)

Hexapeptides of sequential overlapping sequences of beta-lactoglobulin (BLG) were used to probe serum from children with immediate-type cow milk allergy for IgE binding to continuous epitopes of BLG in an enhanced enzyme-linked immunosorbent assay (ELISA). Six regions of IgE binding were identified on the BLG molecule and these were synthesized as dodecapeptides. Inhibition of IgE binding to whole BLG was used to confirm the BLG-specific binding of IgE to each of the synthesized peptides. One of the peptides, peptide 4, showed inhibition in an IgE anti-BLG radioimmunoassay to all 16 sera tested. The patterns of inhibition with the native BLG molecule and peptide 4 were significantly correlated (P = 0.005), suggesting that this peptide contains a major continuous IgE binding epitope of BLG.
Rivastigmine, a Brain-Selective Acetylcholinesterase Inhibitor, Ameliorates Cognitive and Motor Deficits Induced by Closed-Head Injury in the Mouse (1998)

The effects of Rivastigmine, a novel centrally-acting anticholinesterase agent, were evaluated on cerebral edema, neurological and motor deficits, and impairment of spatial memory induced in mice by closed-head injury (CHI). Severe injury was induced in the left hemisphere of mice under ether anesthesia. Rivastigmine (1 or 2 mg/kg) or saline (10 ml/kg) was injected SC 5 min later. Rivastigmine (2 mg/kg) reduced cerebral edema by at least 50% (p < 0.01), 24 h after CHI and accelerated the recovery of motor function 7 and 14 days after CHI. Control mice (n = 24), previously trained to find the goal platform in a Morris water maze failed to recall or relearn its position for at least 11 days post-injury. Those given a single injection of Rivastigmine (2 mg/kg) regained their pre-test latencies by the third day after CHI. The neuroprotective effects of Rivastigmine on brain edema, neurological and motor function, and performance in the Morris water maze were completely antagonized by simultaneous SC injection of either scopolamine (0.5 mg/kg) or mecamylamine (2.5 mg/kg). The antagonists alone had no significant effect on any of these parameters. These data show that the reduction by Rivastigmine of the immediate and long-term sequelae of brain injury are mediated by increased cholinergic activity at both muscarinic and nicotinic receptors.
Reduced cartilage proteoglycan loss during zymosan‐induced gonarthritis in NOS2‐deficient mice and in anti‐interleukin‐1‐treated wild-type mice with unabated joint inflammation (1998)

Objective To investigate the role of nitric oxide (NO) and interleukin-1 in (IL-1) joint inflammation and cartilage destruction during zymosan-induced gonarthritis (ZIA). Methods Monarticular arthritis was elicited by intraarticular injection of zymosan. The effect of NO deficiency on arthritis was studied in mice with genetically disrupted NOS2. The role of IL-1 was examined by treating wild-type mice with neutralizing anti-murine IL-1 (α + β) antibodies. Joint swelling was measured externally by the increased uptake of circulating 99mtechnetium pertechnetate. Proteoglycan (PG) synthesis was assessed using 35S-sulfate incorporation into patellae ex vivo. Histology evaluated exudation and infiltration of leukocytes and the extent of cartilage destruction. Results The proinflammatory mediators NO, IL-1, and IL-6 were released by the articular tissues during the first hours of inflammation. Interestingly, anti-IL-1 treatment moderately reduced, and NOS2 deficiency moderately enhanced, joint swelling. However, the influx of neutrophils into the joint occurred independent of IL-1 and NOS2 activities. In the first week of inflammation, chondrocyte PG synthesis was significantly suppressed and chondrocytes became unresponsive to their essential anabolic factor, insulin-like growth factor 1 (IGF-1). Anti-IL-1 treatment or NOS2 deficiency prevented the inhibition of PG synthesis, and the chondrocytes remained IGF-1 responsive. Intraarticular injections of IL-1α into NOS2-deficient mice did not affect PG synthesis, thus proving that NO mediated this IL-1 effect in vivo. Furthermore, histology showed that cartilage PG loss was markedly ameliorated in NOS2-deficient and anti-IL-1-treated mice. Intermediate cartilage pathology was found in mice that were heterozygous for disrupted NOS2. Conclusion IL-1 and NO play a minor role in edema and neutrophil influx, but a major role in cartilage destruction of ZIA. In this model of murine arthritis, cartilage destruction was, for the most part, caused by pronounced suppression of PG synthesis and IGF-1 unresponsiveness of the chondrocytes, which were induced by the novo-synthesized IL-1 and were mediated by NOS2 activation.
Superparamagnetic core-shell polymer particles for efficient purification of his-tagged proteins (2010)

Magnetic core-shell Fe3O4@SiO2@poly(styrene-alt-maleic anhydride) spheres enriched with Ni-NTA on their surface have been prepared by precipitation polymerization. The spheres have a core composed of superparamagnetic polycrystalline magnetite having a uniform size of ∼220 nm, endowing the spheres with excellent magnetic responsivity and dispersity. The shell composition of poly(styrene-alt-maleic anhydride) allows the incorporation of more Ni-NTA affinity sites onto the surface of the magnetic spheres. Owing to the multivalency effect, the separation capacity of His-tagged proteins by the as-prepared Fe3O4@SiO2@polymer/Ni-NTA composites was four times as that by Fe3O4@SiO2/Ni-NTA, making them particularly promising for the magnetic separation of low-concentration His-tagged proteins. The magnentic polymer hybrid particles also exhibited excellent performance in the direct separation of His-tagged proteins from cells lysates.
Meta-Analysis of Clinical Efficacy of Pulsed Radio Frequency Energy Treatment (2012)

On the basis of statistical evaluation of published clinical efficacy data, there is strong statistical evidence that PRFE therapy is effective in the treatment of postoperative and nonpostoperative pain and edema and in WH applications.
Nitric Oxide (NO) Donor Molecules (1995)

Nitric oxide (NO) inhibits vascular smooth muscle cell (SMC) growth in vitro. To determine the effects of release rate and exposure time on SMC growth inhibition by NO, we compared the activities of five NO donors that generate NO with half-lives of 2 min (DEA/NO, Et2N[N2O2]Na), 15 min (PAPA/NO, CH3(CH2)2N[N2O2]-(CH2)3NH3+), 39 min, (SPER/NO, H2N(CH2)3NH2+(CH2)4N[N2O2]-(CH2)3NH2), 3 h (DPTA/NO, H2N(CH2)3N[N2O2]-(CH2)3NH3+), and 20 h (DETA/NO, H2N(CH2)2N[N2O2]-(CH2)2NH3+). After 22-h treatment, rat aorta SMC (RA-SMC) DNA synthesis was inhibited with IC50 values of 180, 60, and 40 microM for SPER/NO, DPTA/NO, and DETA/NO, respectively. DEA/NO and PAPA/NO did not inhibit DNA synthesis significantly at any concentration tested (20-500 microM). The inhibitory effect of NO on RA-SMC DNA synthesis was thus greatest when a given molar dose of NO was delivered slowly throughout the 22-h period. The antiproliferative effect of DETA/NO was confirmed by measurement of cell numbers for 7 days. When RA-SMC were treated with 500 microM DETA/NO on days 1, 3, and 5, growth was completely suppressed. Cell viability was > 95%, confirming that DETA/NO was not cytotoxic. The results suggest that NO donors may be useful inhibitors of intimal hyperplasia and restenosis after vascular injury such as balloon angioplasty.
The Use of Electromagnetic Motion Tracking Analysis To Objectively Measure Open Surgical Skill in The Laboratory-Based Model (2001)

These findings suggest that hand motion analysis may be an effective objective measure of dexterity in open surgical simulation.
Inhaled p38α Mitogen-activated Protein Kinase Antisense Oligonucleotide Attenuates Asthma in Mice (2004)

The p38 mitogen-activated protein kinase (MAPK) plays a critical role in the activation of inflammatory cells. Therefore, we investigated the antiinflammatory effects of a respirable p38alpha MAPK antisense oligonucleotide (p38alpha-ASO) in a mouse asthma model. A potent and selective p38alpha-ASO was characterized in vitro. Inhalation of aerosolized p38alpha-ASO using an aerosol chamber dosing system produced measurable lung deposition of ASO and significant reduction of ovalbumin (OVA-)-induced increases in total cells, eosinophils, and interleukin 4 (IL-4), IL-5, and IL-13 levels in bronchoalveolar lavage fluid, and dose-dependent inhibition of airway hyperresponsiveness in allergen-challenged mice. Furthermore, inhaled p38alpha-ASO markedly inhibited OVA-induced lung tissue eosinophilia and airway mucus hypersecretion. Quantitative polymerase chain reaction analysis of bronchoalveolar lavage fluid cells and peribronchial lymph node cells showed that p38alpha-ASO significantly reduced p38alpha MAPK mRNA expression. Nose-only aerosol exposure of mice verified the p38alpha-ASO-induced inhibition of OVA-induced pulmonary eosinophilia, mucus hypersecretion, and airway hyperresponsiveness. None of the effects of the p38alpha-ASO were produced by a six-base mismatched control oligonucleotide. These findings demonstrate antisense pharmacodynamic activity in the airways after aerosol delivery and suggest that a p38alpha MAPK ASO approach may have therapeutic potential for asthma and other inflammatory lung diseases.