gebhart/patrepeval huggingface dataset:
Crisscross Enzymatic Reaction between the Two Molecules in the Active Dimeric P69 Form of the 2′-5′ Oligodenylate Synthetase (2002)

2'-5' oligoadenylate (2-5 (A)) synthetases are major components of the antiviral pathways induced by interferons. In the presence of double-stranded RNA, they polymerize ATP to form 2-5 (A) oligomers that, in turn, activate the latent ribonuclease RNase L, causing mRNA degradation. These enzymes, unlike other nucleotidyl transferases, catalyze 2'-5', not 3'-5', phosphodiester bond formation between substrates bound to the acceptor and donor sites. Moreover, unlike other members of this extended family, the P69 isozyme of 2-5 (A) synthetase functions as a homodimer. Here, we report that the need for P69 dimerization is because of a crisscross enzyme reaction joining two substrate molecules bound to two opposite subunits. Consequently, although homodimers of mutants in the previously identified acceptor site, the donor site, or the catalytic site were inactive, selective heterodimers of the mutants were active because of subunit complementation. The catalytic site had to be present in the same subunit that contained the acceptor site, whereas the donor site had to be provided by the other subunit. These results allowed us to design a mutant protein that acted as a dominant-negative inhibitor of wt P69 but not of another isozyme of 2-5 (A) synthetase.
Formation of Vesicular Stomatitis Virus Pseudotypes Bearing Surface Proteins of Hepatitis B Virus (2005)

ABSTRACT It has been difficult to propagate and titrate hepatitis B virus (HBV) in tissue culture. We examined whether vesicular stomatitis virus (VSV) pseudotypes bearing HBV surface (HBs) proteins infectious for human cell lines could be prepared. For this, expression plasmids for three surface proteins, L, M, and S, of HBV were made. 293T cells were then transfected with these plasmids either individually or in different combinations. 293T cells expressing HBs proteins were infected with VSVΔG*-G, a recombinant VSV expressing green fluorescent protein (GFP), to make VSV pseudotypes. Culture supernatants together with cells were harvested and sonicated for a short time. The infectivities of freshly harvested supernatants were determined by quantifying the number of cells expressing GFP after neutralization with anti-VSV serum and mouse monoclonal antibodies (MAbs) against HBs protein. Among 14 cell lines tested for susceptibility to HBV pseudotype samples, HepG2, JHH-7, and 293T cells were judged to be the most susceptible. Namely, the infectious units (IU) of the culture supernatant samples neutralized with anti-VSV in the absence and presence of anti-HBs S MAbs and titrated on HepG2 cells ranged from 1,000 to 4,000 IU/ml and 200 to 400 IU/ml, respectively, suggesting the presence of VSVΔG*(HBV) pseudotypes. This infectivity was inhibited by treatment with lactoferrin or dextran sulfate. Pretreatment of the cells with trypsin or tunicamycin inhibited plating of the pseudotype samples. The HBV pseudotypes can be used to analyze early steps of HBV infection, including the entry mechanism of HBV.
Helical β-Peptide Inhibitors of the p53-hDM2 Interaction (2004)

hDM2 is recognized in vivo by a short alpha-helix within the p53 trans-activation domain (p53AD). Disruption of the p53.hDM2 interaction is an important goal for cancer therapy. A functional epitope comprised of three residues on one face of the p53AD helix (F19, W23, and L26) contributes heavily to the binding free energy. We hypothesized that the p53AD functional epitope would be recapitulated if the side chains of F19, W23, and L26 were presented at successive positions three residues apart on a stabilized beta3-peptide 14-helix. Here, we report a set of beta3-peptides that possess significant 14-helix structure in water; one recognizes a cleft on the surface of hDM2 with nanomolar affinity. The strategy for beta3-peptide design that we describe is general and may have advantages over one in which individual or multiple beta-amino acid substitutions are introduced into a functional alpha-peptide, because it is based on homology at the level of secondary structure, not primary sequence.
Protein secretion from Saccharomyces cerevisiae directed by the prepro-alpha-factor leader region. (1986)

The Saccharomyces cerevisiae secretory process was studied by evaluating secretion efficiency, processing efficiency, and the efficiency of protein folding for hybrid proteins containing the yeast prepro-alpha-factor leader region. Secretion of three proteins, beta-endorphin, calcitonin, and a consensus alpha-interferon (IFN-Con1), were compared in terms of secretion efficiency into the culture medium, beta-Endorphin and calcitonin, both small proteins, were found to be efficiently secreted from logarithmically grown cells. In contrast, the larger IFN-Con1 accumulated in the periplasmic space and cell wall. The glycosylated, unprocessed prepro-alpha-factor/IFN-Con1 fusion protein was also found to be secreted into the culture medium. The presence of (Glu-Ala) dipeptides in the alpha-factor spacer peptide increased the efficiency of cleavage at Lys-Arg in the prepro-alpha-factor/IFN-Con1 protein fusion. Purified secreted IFN-Con1 was structurally characterized to determine the effect of passage through the yeast secretory pathway on the fidelity and efficiency of protein folding. The disulfide structure of the secreted protein was found to be identical with that reported for the native human alpha-interferons.
Effect of pore size on carbon dioxide sorption by carbide derived carbon (2011)

CO2 sorption at atmospheric and sub-atmospheric pressures is a key step towards carbon capture and sequestration (CCS) and materials capable of fast and efficient CO2 uptake are currently being studied extensively. Carbide-derived carbons (CDCs) show a very high sorption capacity for CO2 of up to 7.1 mol/kg at 0 °C and ambient pressure. This value is significantly higher than other carbon materials. Systematic experimental investigation of a large number of different CDCs derived from nano- and micrometer sized precursors with and without activation show a linear correlation between the CO2 uptake at a certain pressure and the pore volume. However, CO2 sorption is not limited by the total pore volume but only by pores smaller than a certain diameter. At 1 bar, pores smaller than 0.8 nm contribute the most to the CO2 uptake and at 0.1 bar pores smaller or equal to 0.5 nm are preferred. With lower total pressure, smaller pores contribute more to the measured amount of adsorbed CO2. The prediction of the CO2 uptake based on the pore volume for pores of a certain diameter is much more accurate than predictions based on the mean pore size or the specific surface area. This study provides guidelines for the design of materials with an improved ability to remove carbon dioxide from the environment at atmospheric and lower pressures.
[Effect of nylestriol on bone remodeling in ovariectomized rats]. (2004)

Nylestriol plays an important role in maintaining bone volume and improving bone microarchitecture by markedly inhibiting bone turnover and bone resorption, which might be to some degree attributed to reduced IL-6 expression.
Electrical resistance across the blood‐brain barrier in anaesthetized rats: a developmental study. (1990)

1. Ion permeability of the blood-brain barrier was studied by in situ measurement of transendothelial electrical resistance in anaesthetized rats aged between 17 days gestation and 33 days after birth, and by electron microscopic examination of lanthanum permeability in fetal and neonatal rats aged up to 10 days old. 2. The blood-brain barrier in 17- to 20-day fetuses had a resistance of 310 omega cm2 but was impermeable to lanthanum, and therefore had properties intermediate between leaky and tight epithelia. 3. From 21 days gestation, the resistance was 1128 omega cm2, indicating a tight blood-brain barrier and low ion permeability. There was little further change in barrier resistance after birth, and in 28- to 33-day rats, when the brain barrier systems are mature in other ways, vessels had a mean resistance of 1462 omega cm2. 4. In the tight blood-brain barrier, arterial vessels had a significantly higher resistance than venous vessels, 1490 and 918 omega cm2 respectively. In vessels less than 50 microns diameter and within the normal 60 min experimental period, there was no significant variation in vessel resistance. 5. Hyperosmotic shock caused a rapid decay in resistance (maximal within 5 min), and after disruption of the blood-brain barrier, vessel resistance was 100-300 omega cm2 in both arterial and venous vessels, and the effect was reversible. After the application of metabolic poisons (NaCN plus iodoacetate) and low temperature there was a similarly low electrical resistance. 6. It is concluded that the increase in electrical resistance at birth indicates a decrease in paracellular ion permeability at the blood-brain barrier and is required for effective brain interstitial fluid ion regulation.
Dendritic cells transduced with wild-type p53 gene elicit potent anti-tumour immune responses (1999)

In this study we have tested the concept of using wild-type p53 gene for immunotherapy of cancer. Dendritic cells (DC) were transduced with a human wild-type p53 containing recombinant adenovirus (Ad-p53). About a half of DC transduced with this virus expressed p53 protein by FACS analysis 48 h after infection. Mice immunized twice with Ad-p53 DC developed substantial cytotoxic T lymphocyte (CTL) responses against tumour cells expressing wild-type and different mutant human and murine p53 genes. Very low CTL responses were observed against target cells infected with control adenovirus (Ad-c). Immunization with Ad-p53 provided complete tumour protection in 85% of mice challenged with tumour cells expressing human mutant p53 and in 72.7% of mice challenged with tumour cells with murine mutant p53. Treatment with Ad-p53-transduced DC significantly slowed the growth of established tumours. Thus, DC transduced with wild-type p53 may be a promising new tool for the immunotherapy of cancer.
Single‐unit muscle sympathetic nervous activity and its relation to cardiac noradrenaline spillover (2011)

Recent work using single-unit sympathetic nerve recording techniques has demonstrated aberrations in the firing pattern of sympathetic nerves in a variety of patient groups. We sought to examine whether nerve firing pattern is associated with increased noradrenaline release. Using single-unit muscle sympathetic nerve recording techniques coupled with direct cardiac catheterisation and noradrenaline isotope dilution methodology we examined the relationship between single-unit firing patterns and cardiac and whole body noradrenaline spillover to plasma. Participants comprised patients with hypertension (n=6), depression (n=7) and panic disorder (n =9) who were drawn from our ongoing studies. The patient groups examined did not differ in their single-unit muscle sympathetic nerve firing characteristics nor in the rate of spillover of noradrenaline to plasma from the heart. The median incidence of multiple spikes per beat was 9%. Patients were stratified according to the firing pattern: low level of incidence (less than 9% incidence of multiple spikes per beat) and high level of incidence (greater than 9% incidence of multiple spikes per beat). High incidence of multiple spikes within a cardiac cycle was associated with higher firing rates (P <0.0001) and increased probability of firing (P <0.0001). Whole body noradrenaline spillover to plasma and (multi-unit) muscle sympathetic nerve activity in subjects with low incidence of multiple spikes was not different to that of those with high incidence of multiple spikes. In those with high incidence of multiple spikes there occurred a parallel activation of the sympathetic outflow to the heart, with cardiac noradrenaline spillover to plasma being two times that of subjects with low nerve firing rates (11.0 ± 1.5 vs. 22.0 ± 4.5 ng min⁻¹, P <0.05). This study indicates that multiple within-burst firing and increased single-unit firing rates of the sympathetic outflow to the skeletal muscle vasculature is associated with high cardiac noradrenaline spillover.
Inhibition of Glycogen Synthase Kinase-3 in Androgen-Responsive Prostate Cancer Cell Lines: Are GSK Inhibitors Therapeutically Useful? (2008)

The glycogen synthase kinase 3 (GSK-3) is a serine/threonine kinase widely expressed in mammalian tissues. Initially identified by its ability to modulate glycogen synthesis, GSK-3 turned out to be a multifunctional enzyme, able to phosphorylate many proteins, including members of the steroid receptor superfamily. Although GSK-3 was shown to phosphorylate the androgen receptor (AR), its effects on AR transcriptional activity remain controversial. Analysis of short hairpin RNA (shRNA)-mediated downmodulation of GSK-3 proteins in prostate cancer cells showed a reduction in AR transcriptional activity and AR protein levels. Pharmacological GSK-3 inhibitors such as the maleimide SB216763 or the aminopyrazole GSK inhibitor XIII inhibited AR-dependent reporter gene activity and AR expression in vitro. Analysis of androgen-induced nuclear translocation of the AR was performed in PC3 cells transfected with pAR-t1EosFP coding for EosAR, a green fluorescent AR fusion protein. When grown in presence of androgens, EosAR was predominantly nuclear. Incubation with SB216763 before and after androgen treatment almost completely reduced nuclear EosAR. In contrast, the thiazole-containing urea compound AR-A014418 increased rather than decreased AR-expression/function. Although not all GSK inhibitors affected AR-stability/function, our observations suggest a potential new therapeutic application for some of these compounds in prostate cancer.
Trajectory control of multirotor helicopters with thrust vector constraints (2013)

The multirotor control system structure that has mostly been adopted is constituted by an inner and an outer control loop. In this scheme, the inner loop carries out attitude control while the outer loop is responsible for trajectory control. The present work addresses the problem of safely controlling the trajectory of a multirotor helicopter by taking into account specified constraints on both the total thrust magnitude and the inclination of the rotor plane. The proposed solution partitions the whole problem into an altitude and an horizontal position control. The control laws of the two parts combine the feedback linearization principle with saturated proportional-derivative controllers. The proposed method is evaluated by computational simulations, which show its effectiveness to control the vehicle along a spiral trajectory as well as respond to abrupt position commands.
LAPAROSCOPIC GASTROSTOMY: TOWARDS THE IDEAL TECHNIQUE (1998)

The described technique is a further advance in defining the 'ideal' technique of laparoscopic gastrostomy.
Elicitation of anti-Sendai virus cytotoxic T lymphocytes by viral and H-2 antigens incorporated into the same lipid bilayer by membrane fusion and by reconstitution into liposomes. (1980)

We have investigated the minimal molecular requirements for elicitation of anti-Sendai virus cytotoxic T lymphocytes (CTL), and the minimal molecular requirements for the recognition and lysis processes associated with anti-Sendai virus CTL-target cell interactions. This report demonstrates a) that the hemagglutinin-neuraminidase and/or fusion glycoproteins of Sendai virus can elicit anti-Sendai virus CTL and b) that these glycoproteins and H-2 antigens must be within the same membrane lipid bilayer for effective elicitation of anti-Sendai-virus CTL and for effective recognition and lysis of target cells by anti-Sendai virus CTL.
Isolation and kinetic characterization of the calmodulin methyltransferase from sheep brain (1993)

The methyltransferase that catalyzes the trimethylation of lysine 115 in calmodulin has been purified from sheep brain. The enzyme is a monomer with an apparent molecular weight of 38,000 on the basis of gel filtration chromatography and SDS-polyacrylamide electrophoresis. In the presence of calcium the methyltransferase exhibited a Km of 100 nM for unmethylated calmodulin and a kcat of 0.0278 s-1. The enzyme was able to use calcium-depleted calmodulin as a substrate, albeit with less efficiency. The methylation of calcium-depleted calmodulin was inhibited by increases in ionic strength, whereas methylation of calcium-saturated calmodulin was not affected. This suggests a difference in the mode of interaction of calcium-saturated and calcium-depleted calmodulins with the enzyme. As with calmodulin's interactions with other calmodulin-dependent enzymes, the oxidation of the methionines of calmodulin by performic acid treatment decreases the ability of the methyltransferase to recognize and methylate calmodulin. A calmodulin-binding peptide based on the calmodulin-dependent protein kinase II sequence and the naphthalenesulfonamide W-7 inhibit the calmodulin methyltransferase-calmodulin interaction in a calcium-dependent manner. Removal of the NH2-terminal lobe (residues 1-77) does not affect the ability of the calmodulin methyltransferase to recognize and methylate lysine 115. Thus, the determinants for calmodulin methyltransferase binding reside solely in the COOH-terminal lobe of calmodulin. Further, structural features within this region, in particular, the hydrophobic cleft, that are manifested upon calcium binding may contribute to the interaction of calmodulin with the enzyme.
PpATG9 Encodes a Novel Membrane Protein That Traffics to Vacuolar Membranes, Which Sequester Peroxisomes during Pexophagy inPichia pastoris (2005)

When Pichia pastoris adapts from methanol to glucose growth, peroxisomes are rapidly sequestered and degraded within the vacuole by micropexophagy. During micropexophagy, sequestering membranes arise from the vacuole to engulf the peroxisomes. Fusion of the sequestering membranes and incorporation of the peroxisomes into the vacuole is mediated by the micropexophagy-specific membrane apparatus (MIPA). In this study, we show the P. pastoris ortholog of Atg9, a novel membrane protein is essential for the formation of the sequestering membranes and assembly of MIPA. During methanol growth, GFP-PpAtg9 localizes to multiple structures situated near the plasma membrane referred as the peripheral compartment (Atg9-PC). On glucose-induced micropexophagy, PpAtg9 traffics from the Atg9-PC to unique perivacuolar structures (PVS) that contain PpAtg11, but lack PpAtg2 and PpAtg8. Afterward, PpAtg9 distributes to the vacuole surface and sequestering membranes. Movement of the PpAtg9 from the Atg9-PC to the PVS requires PpAtg11 and PpVps15. PpAtg2 and PpAtg7 are essential for PpAtg9 trafficking from the PVS to the vacuole and sequestering membranes, whereas trafficking of PpAtg9 proceeds independent of PpAtg1, PpAtg18, and PpVac8. In summary, our data suggest that PpAtg9 transits from the Atg9-PC to the PVS and then to the sequestering membranes that engulf the peroxisomes for degradation.
Nuclear factor‐κB‐dependent reversal of aging‐induced alterations in T cell cytokines (2008)

Immunosenescence is characterized by decreases in protective immune responses and increases in inflammation and autoimmunity. The T helper (Th)17 subset of cluster-of-differentiation (CD)4 T cells, which is identified by its generation of interleukin (IL) -17, is implicated in autoimmune pathogenesis. To elucidate immunosenescent changes in Th17 cell cytokines, splenic CD4 T cells from 22- to 24-month-old (old) mice and 6- to 10-wk-old (young) mice were incubated on anti-CD3 plus anti-CD28 (anti-T cell antigen receptor) antibodies. After 96 h, T cells of old C57BL/6 and CBA mice generated up to 20-fold more IL-17 and up to 3-fold more IL-6 than those of young mice; T cells of young mice generated up to 5-fold more IL-21 than those of old mice; and no difference was found for IFN-gamma. At 24 h, cytokine mRNA levels paralleled 96 h cytokine concentrations. Naive CD4 T cells from old mice incubated on anti-T cell antigen receptor antibodies with transforming growth factor-beta, IL-1, IL-6, and IL-23 to induce de novo differentiation of Th17 cells had more IL-17 mRNA and produced more IL-17 than those of young mice. BAY11-7082 and the phytochemicals triptolide and butein suppressed nuclear concentrations of nuclear factor-kappaB and secreted levels of IL-17, IL-21, and IFN-gamma in parallel, with greater potency in Th17 cells from young than old mice. Pharmacological correction of altered generation of Th17 cell cytokines in immunosenescence represents a novel therapeutic approach to aging-induced inflammatory diseases.
Long-term recurrent convolutional networks for visual recognition and description (2015)

Models based on deep convolutional networks have dominated recent image interpretation tasks; we investigate whether models which are also recurrent, or “temporally deep”, are effective for tasks involving sequences, visual and otherwise. We develop a novel recurrent convolutional architecture suitable for large-scale visual learning which is end-to-end trainable, and demonstrate the value of these models on benchmark video recognition tasks, image description and retrieval problems, and video narration challenges. In contrast to current models which assume a fixed spatio-temporal receptive field or simple temporal averaging for sequential processing, recurrent convolutional models are “doubly deep” in that they can be compositional in spatial and temporal “layers”. Such models may have advantages when target concepts are complex and/or training data are limited. Learning long-term dependencies is possible when nonlinearities are incorporated into the network state updates. Long-term RNN models are appealing in that they directly can map variable-length inputs (e.g., video frames) to variable length outputs (e.g., natural language text) and can model complex temporal dynamics; yet they can be optimized with backpropagation. Our recurrent long-term models are directly connected to modern visual convnet models and can be jointly trained to simultaneously learn temporal dynamics and convolutional perceptual representations. Our results show such models have distinct advantages over state-of-the-art models for recognition or generation which are separately defined and/or optimized.
RNA-Seq and molecular docking reveal multi-level pesticide resistance in the bed bug (2012)

We developed significant molecular resources for C. lectularius putatively involved in metabolic resistance as well as those participating in other modes of insecticide resistance. RNA-Seq profiles of PR strains combined with tissue-specific profiles and molecular docking revealed multi-level insecticide resistance in C. lectularius. Future research that is targeted towards RNA interference (RNAi) on the identified metabolic targets such as cytochrome P450s and cuticular proteins could lay the foundation for a better understanding of the genetic basis of insecticide resistance in C. lectularius.