gebhart/patrepeval huggingface dataset:
Stable Expression and Characterization of Human PN1 and PN3 Sodium Channels (2003)

Nociceptive transduction in inflammatory and neuropathic pain involves peripherally expressed voltage-gated sodium channels, such as tetrodotoxin (TTX)-sensitive PN1 and TTX-resistant PN3. We generated recombinant cell lines stably expressing the human PN1 and PN3 sodium channels in Chinese hamster ovary (CHO) cells using inducible expression vectors. The PN1 and PN3 cDNAs were isolated from human adrenal gland and heart poly(A)+ RNAs, respectively. The recombinant human PN1 currents exhibited rapid activation and inactivation kinetics and were blocked by TTX with a half-maximal inhibitory concentration (IC50) of 32.6 nM. The human PN3 channel expressed in stable transfectants showed TTX-resistant inward currents with slow inactivation kinetics. The IC50 value for TTX was 73.3 microM. The voltage-dependence of activation of the PN3 channel was shifted to the depolarizing direction, compared to that of the PN1 channel. Lidocaine and mexiletine exhibited tonic and use-dependent block of PN1 and PN3 channels. The PN1 channel was more susceptible to inhibition by mexiletine than PN3. These results suggest that stable transfectants expressing the human PN1 and PN3 sodium channels will be useful tools to define subtype selectivity for sodium channel blockers.
Adhesion molecules in renal disease (1996)

This review updates the advances in basic and clinical studies of adhesion molecules in renal disease that have appeared in 1995. The primary focus is on ischemia and transplantation.
Lipid emulsion is superior to vasopressin in a rodent model of resuscitation from toxin-induced cardiac arrest* (2009)

Lipid emulsion in this rat model provides superior hemodynamic and metabolic recovery from bupivacaine-induced cardiac arrest than do vasopressors. Systolic pressure was not a useful metric in the vasopressor groups. Vasopressin was associated with adverse outcomes.
Structure and Function of the Factor VIII Gene and Protein (2003)

Factor (F) VIII is a large gene located near the terminus of the long arm of the X chromosome. It contains 26 exons that code for a signal peptide and a 2332 amino acid polypeptide with three different types of domains, namely A1-A2-B-A3-C1-C2. The A domains are homologous with each other and those of ceruloplasmin; substitution into the known crystal structure of the copper binding protein produces molecular models. The large, central B domain is highly glycosylated but has a variable sequence, even among FVIIIs from different species. Most of B can be deleted and the resulting recombinant protein has essentially normal survival in circulation and corrects the bleeding tendency in hemophilia A patients. The C domains are similar to each other, and the crystal structure of a recombinant human C2 domain is known, allowing construction of a molecular model of C1. The FVIII protein is secreted as a heterodimer following at least two intracellular cleavages within the B domain. In circulation it is stabilized by binding to von Willebrand factor (vWF) with a plasma half-life of about 10 hours. After specific thrombin cleavages that remove the remainder of the B domain and one of the high-affinity von Willebrand factor binding sites, FVIII becomes heterotrimeric FVIIIa, capable of enhancing intrinsic FX activation by FIXa. Inactivation of FVIIIa occurs by A2 dissociation or by specific cleavages within A1 and A2 by activated protein C. Control of intrinsic FX activation is critical for hemostasis and thrombosis.
Naive versus memory CD4 T cell response to antigen. Memory cells are less dependent on accessory cell costimulation and can respond to many antigen-presenting cell types including resting B cells. (1994)

Secondary responses to Ag in vivo are characterized by more rapid kinetics and greatly enhanced magnitude compared with primary responses. For CD4+ T cells, this is in part due to a greater frequency of Ag-specific memory cells, and may also reflect differences in responsiveness of memory vs naive cells to stimulation. To compare activation requirements and the role of accessory cells, naive and memory cells were stimulated with immobilized anti-CD3 in the presence or absence of APC. With anti-CD3 alone, naive cells proliferated slightly but produced no detectable IL-2, whereas memory cells proliferated well with significant IL-2 production. Increasing numbers of T-depleted APC greatly enhanced responses of naive cells to levels equivalent to those of memory cells, whereas for memory cells only IL-2 production increased slightly. The response of naive cells was equivalent in magnitude and kinetics to that of memory cells when low density APC, enriched in dendritic cells and depleted of resting B cells, were used with anti-CD3. To directly compare naive and memory responses in an Ag-specific model, we examined CD4+ cells specific for a peptide of pigeon cytochrome c fragment isolated from TCR-alpha beta transgenic mice. Naive cells were compared with 4-day activated blasts (effectors) and memory cells generated by adoptive transfer of effectors to adult thymectomized bone marrow reconstituted mice, in which the cells return to a resting state but still respond to recall Ag. Naive cells responded to Ag on dendritic cells and activated B cells but not on resting B cells or macrophages. In contrast, both memory cells and effectors were stimulated by all APCs, including resting B cells and macrophage to a limited extent. The ability of memory cells to respond to all APC types was confirmed using Ag-specific cells generated by in vivo priming with keyhole limpet hemocyanin. These results suggest that memory cells are considerably less dependent on accessory cell costimulation than naive cells, but that naive cells can respond equivalently in both magnitude and kinetics if Ag is presented on costimulatory APCs such as dendritic cells. In addition, these studies suggest that the enhanced secondary T cell response is due to a combination of the increased frequency of Ag-specific cells and their ability to react to Ag presented on a wider range of APC types, rather than an inherent capacity of memory T cells to respond better and faster.
Generation and Characterization of Monoclonal Antibodies Against the Proregion of Human Desmoglein-2 (2008)

Abstract Cadherins are synthesized with a signal sequence and a proregion that must be removed for optimal adhesive activity. Mutations that prevent processing of cadherins have been implicated in a number of human diseases; thus understanding their processing is critical. In this study, we produced and characterized a number of monoclonal antibodies against the proregion of the desmosomal cadherin, human desmoglein-2, that will facilitate investigations into the processing of this protein.
Strategy for comprehensive identification of human N‐myristoylated proteins using an insect cell‐free protein synthesis system (2010)

To establish a strategy for the comprehensive identification of human N-myristoylated proteins, the susceptibility of human cDNA clones to protein N-myristoylation was evaluated by metabolic labeling and MS analyses of proteins expressed in an insect cell-free protein synthesis system. One-hundred-and-forty-one cDNA clones with N-terminal Met-Gly motifs were selected as potential candidates from approximately 2000 Kazusa ORFeome project human cDNA clones, and their susceptibility to protein N-myristoylation was evaluated using fusion proteins, in which the N-terminal ten amino acid residues were fused to an epitope-tagged model protein. As a result, the products of 29 out of 141 cDNA clones were found to be effectively N-myristoylated. The metabolic labeling experiments both in an insect cell-free protein synthesis system and in the transfected COS-1 cells using full-length cDNA revealed that 27 out of 29 proteins were in fact N-myristoylated. Database searches with these 27 cDNA clones revealed that 18 out of 27 proteins are novel N-myristoylated proteins that have not been reported previously to be N-myristoylated, indicating that this strategy is useful for the comprehensive identification of human N-myristoylated proteins from human cDNA resources.
Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade (2012)

The transthyretin amyloidoses (ATTR) are invariably fatal diseases characterized by progressive neuropathy and/or cardiomyopathy. ATTR are caused by aggregation of transthyretin (TTR), a natively tetrameric protein involved in the transport of thyroxine and the vitamin A-retinol-binding protein complex. Mutations within TTR that cause autosomal dominant forms of disease facilitate tetramer dissociation, monomer misfolding, and aggregation, although wild-type TTR can also form amyloid fibrils in elderly patients. Because tetramer dissociation is the rate-limiting step in TTR amyloidogenesis, targeted therapies have focused on small molecules that kinetically stabilize the tetramer, inhibiting TTR amyloid fibril formation. One such compound, tafamidis meglumine (Fx-1006A), has recently completed Phase II/III trials for the treatment of Transthyretin Type Familial Amyloid Polyneuropathy (TTR-FAP) and demonstrated a slowing of disease progression in patients heterozygous for the V30M TTR mutation. Herein we describe the molecular and structural basis of TTR tetramer stabilization by tafamidis. Tafamidis binds selectively and with negative cooperativity (K(d)s ~2 nM and ~200 nM) to the two normally unoccupied thyroxine-binding sites of the tetramer, and kinetically stabilizes TTR. Patient-derived amyloidogenic variants of TTR, including kinetically and thermodynamically less stable mutants, are also stabilized by tafamidis binding. The crystal structure of tafamidis-bound TTR suggests that binding stabilizes the weaker dimer-dimer interface against dissociation, the rate-limiting step of amyloidogenesis.
The thermodynamics of the formation of complexes between diethylenetriaminepenta-acetic acid and the lanthanide ions (1968)

The changes in enthalpy accompanying the formation of complexes between diethylenetriaminepenta-acetic acid and the lanthanide ions, in aqueous solution at 27° and an ionic strength of 0·1M, have been measured using an isothermal fusion calorimeter. The enthalpies of complexing have been combined with the appropriate free energy changes to give the entropy changes. The factors which influence the stability of these complexes have been discussed.
Prevention of Myopia Onset with 0.025% Atropine in Premyopic Children (2010)

Regular topical administration of 0.025% atropine eye drops can prevent myopia onset and myopic shift in premyopic schoolchildren for a 1-year period.
Elements of trusted multicasting (2002)

Multicast is rapidly becoming an important mode of communication as well as a good platform for building group-oriented services. However, to be used for trusted communication, current multicast schemes must be supplemented by mechanisms for protecting traffic, controlling participation, and restricting access of unauthorized users to the data exchanged by the participants. We consider fundamental security issues in building a trusted multicast facility. We discuss techniques for group-based data encryption, authentication of participants, and preventing unauthorized transmissions and receptions.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Combined arteriovenous sheathotomy and intraoperative intravitreal triamcinolone acetonide for branch retinal vein occlusion (2010)

For patients with persistent macular oedema due to BRVO refractory to pharmacotherapy and/or laser photocoagulation, concomitant pars plana vitrectomy with arteriovenous sheathotomy and intravitreal triamcinolone may improve best-corrected acuity and reduce macular oedema on fluorescein angiography and OCT.
Histone acetylation and deacetylation: importance in inflammatory lung diseases (2005)

Inflammatory lung diseases are characterised by increased expression of multiple inflammatory genes that are regulated by proinflammatory transcription factors, such as nuclear factor-kappa B. Gene expression is regulated by acetylation of core histones through the action of coactivators, such as CREB-binding protein, with intrinsic histone acetyltransferase (HAT) activity. Conversely, gene repression is mediated via histone deacetylases (HDACs) and other corepressors. In asthma, there is an increase in HAT activity and some reduction in HDAC activity, which is restored by corticosteroid therapy. Corticosteroids switch off inflammatory genes in asthma through the inhibition of HAT activity and by the recruitment of HDAC2 to the activated inflammatory gene complex. In chronic obstructive pulmonary disease, there is a reduction in HDAC2 activity and expression, which may account for the amplified inflammation and resistance to the actions of corticosteroids. The reduction in HDAC2 may be secondary to oxidative and nitrative stress as a result of cigarette smoking and severe inflammation, and may also occur in severe asthma, smoking asthmatic patients and cystic fibrosis. Similar mechanisms may also account for the steroid resistance seen with latent adenovirus infections. The reduction in histone deacetylase activity can be restored by theophylline, which may be able to reverse steroid resistance in chronic obstructive pulmonary disease and other inflammatory diseases.
Sucker Rod Centralizers for Directional Wells (1990)

ABSTRACT The industry trend towards directional and horizontal wells demands development and use of new equipment to solve the problems raised by the well deviation angle. Perhaps, the strongest limitation for the use of sucker rod pumping in directional and horizontal wells is the early failure of the tubing and sucker rod string. This is caused by the severe wearing of these components due to the continuos friction between them. The life of the subsurface pump life is strongly affected by stem misalignment All these problems are seriously increased if the well has been steam injected. A Sucker rod centralizer, has been developed to reduce the wearing of the tubing, sucker rod string and subsurface pump. So far, centralizers have been installed in seven deviated wells in the Orinoco Belt Field. The use of these centralizers has resulted in a 300% increase of the active life of tubing, sucker rod string and subsurface pumps. These seven wells were steam injected and are producing under an emulsion scheme.
The Endoplasmic Reticulum: Folding, Calcium Homeostasis, Signaling, and Redox Control (2006)

The endoplasmic reticulum (ER) plays a major role in regulating synthesis, folding, and orderly transport of proteins. It is also essentially involved in various cellular signaling processes, primarily by its function as a dynamic Ca(2+) store. Compared to the cytosol, oxidizing conditions are found in the ER that allow oxidation of cysteine residues in nascent polypeptide chains to form intramolecular disulfide bonds. However, compounds and enzymes such as PDI that catalyze disulfide bonds become reduced and have to be reoxidized for further catalytic cycles. A number of enzymes, among them products of the ERO1 gene, appear to provide oxidizing equivalents, and oxygen appears to be the final oxidant in aerobic living organisms. Thus, protein oxidation in the ER is connected with generation of reactive oxygen species (ROS). Changes in the redox state and the presence of ROS also affect the Ca(2+) homeostasis by modulating the functionality of ER-based channels and buffering chaperones. In addition, a close relationship exists between oxidative stress and ER stress, which both may activate signaling events leading to a rebalance of folding capacity and folding demand or to cell death. Thus, redox homeostasis appears to be a prerequisite for proper functioning of the ER.
Nop2p Is Required for Pre-rRNA Processing and 60S Ribosome Subunit Synthesis in Yeast (1997)

To investigate the function of the nucleolar protein Nop2p in Saccharomyces cerevisiae, we constructed a strain in which NOP2 is under the control of a repressible promoter. Repression of NOP2 expression lengthens the doubling time of this strain about fivefold and reduces steady-state levels of 60S ribosomal subunits, 80S ribosomes, and polysomes. Levels of 40S subunits increase as the free pool of 60S subunits is reduced. Nop2p depletion impairs processing of the 35S pre-rRNA and inhibits processing of 27S pre-rRNA, which results in lower steady-state levels of 25S rRNA and 5.8S rRNA. Processing of 20S pre-rRNA to 18S rRNA is not significantly affected. Processing at sites A2, A3, B1L, and B1S and the generation of 5' termini of different pre-rRNA intermediates appear to be normal after Nop2p depletion. Sequence comparisons suggest that Nop2p may function as a methyltransferase. 2'-O-ribose methylation of the conserved site UmGm psi UC2922 is known to take place during processing of 27S pre-rRNA. Although Nop2p depletion lengthens the half-life of 27S pre-RNA, methylation of UmGm psi UC2922 in 27S pre-rRNA is low during Nop2p depletion. However, methylation of UmGm psi UC2922 in mature 25S rRNA appears normal. These findings provide evidence for a close interconnection between methylation at this conserved site and the processing step that yields the 25S rRNA.
C-terminal processing of human beta-glucuronidase. The propeptide is required for full expression of catalytic activity, intracellular retention, and proper phosphorylation. (1993)

beta-Glucuronidase undergoes proteolytic C-terminal processing during or after its transport to lysosomes or endosomes. We determined the C-terminal processing site for human placental beta-glucuronidase to be the peptide bond between Thr633-Arg634. To evaluate the role of the 18-amino acid peptide removed in C-terminal processing, we changed the codon for Arg634 to a stop codon by site-directed mutagenesis and studied expression of the truncated mutant enzyme in COS-7 cells. An increased fraction of newly synthesized enzyme from R634Stop cDNA was secreted. Pulse-chase experiments provided no evidence for increased degradation of the intracellular R634Stop enzyme. The total amount of catalytic activity expressed from the R634Stop mutant cDNA was only half that seen with the wild type cDNA, and the Kcat of the mutant enzyme was 52% that of wild type enzyme. These results indicate that the C-terminal propeptide in the precursor is important for beta-glucuronidase to achieve maximal activity. The truncated enzyme formed hybrid tetramers in cotransfection experiments with the cDNA for rat beta-glucuronidase. There appeared to be no decrease in stability of the R634Stop enzyme, since chaotropic agents, heat treatment, and pH had similar effects on the mutant and the wild type enzymes. The uptake rate of the truncated mutant (R634Stop) enzyme by beta-glucuronidase-deficient human fibroblast cells was only 55-60% that of the wild type enzyme. Binding to the immobilized cation-independent mannose-6-phosphate receptor and measurement of the 32P-labeled phosphorylated oligosaccharides revealed that the truncated mutant enzyme was 32-34% less phosphorylated and appeared to contain proportionately more covered phosphate groups than the wild type enzyme. These results suggest that the propeptide influences the accessibility to both processing enzymes that produce the mannose-6-phosphate recognition marker on beta-glucuronidase.
Isolation and characterization of plant growth-promoting rhizobacteria from wheat roots by wheat germ agglutinin labeled with fluorescein isothiocyanate (2012)

Thirty-two isolates were obtained from wheat rhizosphere by wheat germ agglutinin (WGA) labeled with fluorescein isothiocyanate (FITC). Most isolates were able to produce indole acetic acid (65.6%) and siderophores (59.3%), as well as exhibited phosphate solubilization (96.8%). Fourteen isolates displayed three plant growth-promoting traits. Among these strains, two phosphate-dissolving ones, WS29 and WS31, were evaluated for their beneficial effects on the early growth of wheat (Triticum aestivum Wan33). Strain WS29 and WS31 significantly promoted the development of lateral roots by 34.9% and 27.6%, as well as increased the root dry weight by 25.0% and 25.6%, respectively, compared to those of the control. Based on 16S rRNA gene sequence comparisons and phylogenetic positions, both isolates were determined to belong to the genus Bacillus. The proportion of isolates showing the properties of plant growth-promoting rhizobacteria (PGPR) was higher than in previous reports. The efficiency of the isolation of PGPR strains was also greatly increased by WGA labeled with FITC. The present study indicated that WGA could be used as an effective tool for isolating PGPR strains with high affinity to host plants from wheat roots. The proposed approach could facilitate research on biofertilizers or biocontrol agents.
Mechanisms Regulating Cell Number and Type in the Mammalian Central Nervous System (1990)

In the developing brain, neurons are derived from multipotential precursor cells in a precise sequence, where the time when a neuron becomes postmitotic is closely linked to the differentiated function of the neuron. Work from our group (1) identifies the Nes+ neuronal precursor state, (2) defines growth factors that regulate the proliferation of Nes+ precursor cells and their differentiation into neurons, and (3) establishes immortal cell lines that may be useful models for the terminal differentiation of Nes+ cells into neurons and astrocytes. These results suggest that the basic technical requirements are now in place to define the signals that control the transition from a precursor cell to a postmitotic neuron in the mammalian CNS. Control of this terminal differentiation is a key step in generating the large numbers and types of cells in the CNS.
P‐156: The Focal Surface of a Wedge Projection Display (2005)

Abstract An image from an unmodified projector can be projected through a thin wedge‐shaped panel with little distortion or defocus. This article explains why and describes the focal surface which is presented to the projection lens. A lens design may be optimised for wedge projection using this surface and conventional ray‐tracing software.
<title>Physical characterization and optimal magnification of a portal imaging system</title> (1992)

One problem in radiation therapy is ensuring accurate positioning of the patient so that the prescribed dose is delivered to the diseased regions while healthy tissues are spared. Positioning is usually assessed by exposing film to the high-energy treatment beam. Unfortunately, these films exhibit poor image quality (primarily due to low subject contrast) and the development delays make film impractical to check patient positioning routinely. Therefore, we have been developing a digital video-based imaging system to replace film. The system consists of a copper plate/fluorescent screen detector, a 45 degree(s) mirror, and a TV camera equipped with a large aperture lens. We have determined the signal and noise transfer properties of the imaging system by measuring its MTF(f) and NPS(f) and used these valued to estimate the optimal magnification for the imaging system. We have found that the optimal magnification is 2.3 - 2.5 when optimizing signal transfer (spatial resolution) alone; however, the optimal magnification is only 1.5 - 2.0 if SNR transfer is considered.