gebhart/patrepeval huggingface dataset:
Properties of the (DSS)n triplet repeat domain of rat dentin phosphophoryn (1998)

Phosphophoryns (PPs) are unique aspartic acid and phosphoserine-rich proteins present in all species of dentin. Rat incisor odontoblast cDNA libraries contain messages encoding several acidic phosphorylated, serine-rich proteins. At least two of these share a common C-terminal domain coding region sequence. The polypeptide sequences in the N-terminal direction immediately adjacent to the conserved C-terminal domains of these two proteins (DMP2, DMP3) are distinctly different. In this domain, the DMP2 has extensive sequences of (DSS)n repeats with n as large as 24. DMP3 has fewer and shorter triplet sequences, n = 3, 4. The major rat incisor PPs (90-95 kDa) probably have the (DSS)n>>3. We propose that the name phosphophoryn be reserved for the extracellular matrix proteins with these extended repeats. DMPI, although strongly acidic, does not fit this category. If the S residues are phosphorylated and n > 3, conformational energy minimization computations show the (DSS)n sequence to assume a unique extended structure with parallel arrays of carboxylate and phosphate groups which may function as Ca2+ ion interaction edges. The phosphorylation of recombinant DMP2 C-terminal domain by various kinases has been examined. The repeat domains are not direct substrates for the CK2-like kinases but the kinases act in concert, so that the phosphorylation is hierarchical, apparently controlled by the presence of specific interruptions between the triplet domains.
The course of etoposide‐induced apoptosis in Jurkat cells lacking p53 and Bax (2006)

Jurkat T-lymphocytes lack p53 and Bax but contain p73 and Bid and are killed by etoposide (ETO). With ETO c-abl is phosphorylated and phosphorylated p73 increased. Translocation of full-length Bid to mitochondria follows, with induction of the mitochondrial permeability transition (MPT) and release of cytochrome c into the cytosol. Pronounced swelling of mitochondria was evident ultrastructurally, and the MPT inhibitor cyclosporin A prevented the release of cytochrome c. Overexpression of Bcl-2 prevented the translocation of Bid, the release of cytochrome c, and cell death. The pan-caspase inhibitor ZVAD-FMK prevented the cell killing, but not the initial release of cytochrome c. An accumulation of tBid occurred at later times in association with Bid degradation. A sequence is proposed that couples DNA damage to Bid translocation via activation of c-abl and p73. Bid translocation induces the MPT, the event that causes release of cytochrome c, activation of caspases, and cell death.
Differential Requirement for CD28/CTLA-4-CD80/CD86 Interactions in Drug-Induced Type 1 and Type 2 Immune Responses to Trinitrophenyl-Ovalbumin (2005)

The use of mAbs to abrogate costimulatory interactions has attracted much attention with regard to prevention and modulation of adverse (auto)immune-like reactions. However, the role of costimulatory molecules and possible therapeutic use of Ab-treatment in drug-induced immunostimulation is poorly elucidated. In the present studies, we show that CD28/CTLA-4-CD80/CD86 costimulatory interactions differently regulate drug-induced type 1 and type 2 responses to an identical bystander Ag, TNP-OVA, in BALB/c mice using the reporter Ag popliteal lymph node assay. The antirheumatic drug D-Penicillamine, which may induce lupus-like side-effects, stimulated type 2 responses against TNP-OVA, characterized by the production of IL-4 and TNP-specific IgG1 and IgE. These responses were abrogated in CD80/CD86-deficient mice and in wild-type mice that were treated with anti-CD80 and anti-CD86, or CTLA-4-Ig. Anti-CTLA-4 intensively enhanced the D-Penicillamine-induced effects. In contrast, the type 1 response (IFN-gamma, TNF-alpha, IgG2a) to TNP-OVA induced by the diabetogen streptozotocin still developed in the absence of CD80/CD86 costimulatory signaling. In addition, it was demonstrated that coadministration of anti-CD80 and anti-CD86 mAbs slightly enhanced streptozotocin-induced type 1 responses, whereas the CTLA-4-Ig fusion protein completely abrogated this response. In conclusion, different drugs may stimulate distinct types of immune responses against an identical bystander Ag, which are completely dependent on (type 2) or independent of (type 1) the CD28/CTLA-4-CD80/CD86 pathway. Importantly, the effects of treatment with anti-CD80/CD86 mAbs and CTLA-4-Ig may be considerably different in responses induced by distinct drugs.
Transpubic Suspension of the Bladder Neck for Urinary Incontinence (1980)

We present a modification of the classic Marshall-Marchetti-Krantz procedure in which only 1 pair of sutures is used. Each suture snugs the periurethral tissue of the anterior vaginal wall on each side to the posterior surface of the symphysis pubis and ipsilateral pubic bone by passing the suture through a hole drilled in each respective pubic bone. Complications have been temporary difficulty in voiding after the catheter has been removed and an occasional incisional hernia. Osteitis pubis has not been a problem possibly because of the use of wide-spectrum antibiotics.
Frequency analysis and sheared reconstruction for rendering motion blur (2009)

Motion blur is crucial for high-quality rendering, but is also very expensive. Our first contribution is a frequency analysis of motion-blurred scenes, including moving objects, specular reflections, and shadows. We show that motion induces a shear in the frequency domain, and that the spectrum of moving scenes can be approximated by a wedge. This allows us to compute adaptive space-time sampling rates, to accelerate rendering. For uniform velocities and standard axis-aligned reconstruction, we show that the product of spatial and temporal bandlimits or sampling rates is constant, independent of velocity. Our second contribution is a novel sheared reconstruction filter that is aligned to the first-order direction of motion and enables even lower sampling rates. We present a rendering algorithm that computes a sheared reconstruction filter per pixel, without any intermediate Fourier representation. This often permits synthesis of motion-blurred images with far fewer rendering samples than standard techniques require.
Isoform-Specific Activation of Latent Transforming Growth Factor β (LTGF-β) by Reactive Oxygen Species (2006)

Jobling, M. F., Mott, J. D., Finnegan, M. T., Jurukovski, V., Erickson, A. C., Walian, P. J., Taylor, S. E., Ledbetter, S., Lawrence, C. M., Rifkin, D. B. and Barcellos-Hoff, M. H. Isoform-Specific Activation of Latent Transforming Growth Factor β (LTGF-β) by Reactive Oxygen Species. Radiat. Res. 166, 839–848 (2006).The three mammalian transforming growth factor β (TGF-β) isoforms are each secreted in a latent complex in which TGF-β homodimers are non-covalently associated with homodimers of their respective pro-peptide called the latency-associated peptide (LAP). Release of TGF-β from its LAP, called activation, is required for binding of TGF-β to cellular receptors, making extracellular activation a critical regulatory point for TGF-β bioavailability. Our previous work demonstrated that latent TGF-β1 (LTGF-β1) is efficiently activated by ionizing radiation in vivo and by reactive oxygen species (ROS) generated by Fenton chemistry in vitro. In the current study, we determined the specific ROS and protein target that render LTGF-β1 redox sensitive. First, we compared LTGF-β1, LTGF-β2 and LTGF-β3 to determine the generality of this mechanism of activation and found that redox-mediated activation is restricted to the LTGF-β1 isoform. Next, we used scavengers to determine that ROS activation was a function of OH· availability, confirming oxidation as the primary mechanism. To identify which partner of the LTGF-β1 complex was functionally modified, each was exposed to ROS and tested for the ability to form a latent complex. Exposure of TGF-β1 did not alter its ability to associate with LAP, but exposing LAP-β1 to ROS prohibited this phenomenon, while treatment of ROS-exposed LAP-β1 with a mild reducing agent restored its ability to neutralize TGF-β1 activity. Taken together, these results suggest that ROS-induced oxidation in LAP-β1 triggers a conformational change that releases TGF-β1. Using site-specific mutation, we identified a methionine residue at amino acid position 253 unique to LAP-β1 as critical to ROS-mediated activation. We propose that LTGF-β1 contains a redox switch centered at methionine 253, which allows LTGF-β1 to act uniquely as an extracellular sensor of oxidative stress in tissues.
Identification of immunoreactive proteins ofChlamydia trachomatis by Western blot analysis of a two-dimensional electrophoresis map with patient sera (1999)

Western blots of two-dimensional electrophoretic maps of proteins from Chlamydia trachomatis were probed with sera from 17 seropositive patients with genital inflammatory disease. Immunoblot patterns (comprising 28 to 2 spots, average 14.8) were different for each patient; however, antibodies against a spot-cluster due to the chlamydia-specific antigen outer membrane protein-2 (OMP2) were observed in all sera. The next most frequent group of antibodies (15/17; 88%) recognized the hsp60 GroEL-like protein, described as immunopathogenic in chlamydial infections. Reactivity to the major surface-exposed and variable antigen major outer membrane protein (MOMP) was observed at a relatively lower frequency (13/17; 76%). The hsp70 DnaK-like protein was also frequently recognized (11/17; 64.7%) in this patient group. Besides the above confirmatory findings, the study detected several new immunoreactive proteins, with frequencies ranging from 11/17 to 1/17. Some were characterized also by N-terminal amino acid sequencing and homology searches. Amongst these were a novel outer membrane protein (OmpB) and, interestingly, five conserved bacterial proteins: four (23%) sera reacted with the RNA polymerase alpha-subunit, five (29%) recognized the ribosomal protein S1, eight (47%) the protein elongation factor EF-Tu, seven (41%) a putative stress-induced protease of the HtrA family, and seven sera (41%) the ribosomal protein L7/L12. Homologs of the last two proteins were shown to confer protective immunity in other bacterial infections. The data show that immunological sensitization processes commonly thought to play a role in chlamydial pathogenicity may be sustained not only by the hsp60 GroEl-like protein, but also by other conserved bacterial antigens, some of which may be also considered as potential vaccine candidates.
The Culture of Bovine Oocytes to Obtain Developmentally Competent Embryos1 (1988)

Bovine cumulus-oocyte complexes (COC) (n = 4230) were used in this study to assess the effects of culture method, hormonal supplementation, and cumulus cell concentration on maturation, fertilization and development of resulting embryos. Five treatments were evaluated. 1) 10 COC/50-microliter drops under oil in TCM 199 supplemented with 10% heat-treated fetal calf serum, follicle-stimulating hormone (0.5 microgram/ml), luteinizing hormone (5 micrograms/ml), and estradiol-17 beta (1 microgram/ml); 2) as in 1 without hormones; 3) as in 1 but in 3 ml TCM-199 in petri dishes without paraffin oil; 4) as in 2 but only 1 COC/50-microliter drop; and 5) as in 1 but with denuded oocytes. After 24 h maturation, the frequencies of oocytes reaching metaphase II were 98, 84, 92, 93, and 87%, respectively, for the five treatments. In the same order, percentages of normal fertilization were 73, 70, 62, 81, and 62%, and the frequencies of embryos containing two or more blastomeres at 65 h postinsemination were 69, 82, 66, 51, and 43%. The same five treatments were used in a second study in which 3,199 oocytes were fertilized, allowed to cleave in vitro to the 2- to 3-cell stage (42 h postinsemination), and transferred to oviducts of sheep (one treatment/oviduct) for 4 days. The frequencies of morulae or blastocytes obtained were 28, 18, 23, 24, and 11% for the five treatments, respectively. After nonsurgical transfer to bovine recipients (n = 8) using fresh or frozen-thawed embryos, three pregnancies past 50 days were obtained. Only one went to term with the birth of a live heifer calf.
The reliability of the Neonatal Oral‐Motor Assessment Scale (2008)

NOMAS should be re-adjusted in order to improve inter-rater agreement, and at the same time current insights into the development of sucking and swallowing should be incorporated in the method.
Lentiviral vectors containing the human immunodeficiency virus type-1 central polypurine tract can efficiently transduce nondividing hepatocytes and antigen-presenting cells in vivo (2002)

High-titer self-inactivating human immunodeficiency virus type-1 (HIV-1)-based vectors expressing the green fluorescent protein reporter gene that contained the central polypurine and termination tract and the woodchuck hepatitis virus posttranscriptional regulatory element were constructed. Transduction efficiency and biodistribution were determined, following systemic administration of these improved lentiviral vectors. In adult severe combined immunodeficiency (SCID) mice, efficient stable gene transfer was achieved in the liver (8.0% +/- 6.0%) and spleen (24% +/- 3%). Most transduced hepatocytes and nonhepatocytes were nondividing, thereby obviating the need to induce liver cell proliferation. In vivo gene transfer with this improved lentiviral vector was relatively safe since liver enzyme concentration in the plasma was only moderately and transiently elevated. In addition, nondividing major histocompatibility complex class II-positive splenic antigen-presenting cells (APCs) were efficiently transduced in SCID and normal mice. Furthermore, B cells were efficiently transduced, whereas T cells were refractory to lentiviral transduction in vivo. However, in neonatal recipients, lentiviral transduction was more widespread and included not only hepatocytes and splenic APCs but also cardiomyocytes. The present study suggests potential uses of improved lentiviral vectors for gene therapy of genetic blood disorders resulting from serum protein deficiencies, such as hemophilia, and hepatic disease. However, the use of liver-specific promoters may be warranted to circumvent inadvertent transgene expression in APCs. In addition, these improved lentiviral vectors could potentially be useful for genetic vaccination and treatment of perinatal cardiac disorders.
Supramolecular Polymer Interactions Based on the Alternating Copolymer of Styrene and Maleimide (1995)

No abstract.
Botulinum Toxin Type A for the Treatment of Glabellar Lines in Chinese: A Double-Blind, Randomized, Placebo-Controlled Study (2009)

A single treatment of 20 U of BoNTA was effective and safe in reducing glabellar lines in Chinese subjects.
Class-E amplifier with an inductive impedance inverter (1990)

A design procedure and experimental results are presented for a class-E amplifier with an inductive impedance inverter. Experimental waveforms and characteristics measured at 1 MHz with an IRF620 MOSFET are given for the amplifier, which can operate under zero-voltage switching conditions for load resistances ranging from a short circuit to an open circuit. As the load resistance is increased at a fixed frequency, (1) the output power decreases, (2) a maximum efficiency of 96% occurs for optimum operation, (3) the peak values of the transistor voltage and the transistor current decrease, (4) the normalized peak values of the transistor voltage decrease, and (5) the normalized peak values of the transistor current increase.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A Surprising Recipe for Designing Biased Ligands (2018)

The determination of the potential value of receptor trafficking at melanocortin receptors has been hampered by the absence of known biased ligands. Heterobivalent MC4R ligands linking agonist to antagonist small peptidic moieties were designed and found to act as Gαs enhancers while minimally activating β-arrestin recruitment. The strategy invoked offers intriguing promise as a surprising approach that is possibly broadly applicable to the challenge of designing biased ligands at other GPCRs.
Micronization by Rapid Expansion of Supercritical Solutions to Enhance the Dissolution Rates of Poorly Water-Soluble Pharmaceuticals (2000)

The dissolution of a drug into the biological environment can be enhanced by reducing the particle size of the drug. In this study the rapid expansion of supercritical solutions (RESS) process was employed to micronize racemic ibuprofen, and the dissolution rate of the micronized product in a buffered solution was examined. The chiral nonsteroidal antiinflammatory, racemic ibuprofen, was used as a model drug because its dissolution rate is limited by its poor solubility in water. The phase behavior of the ibuprofen−CO2 binary system was investigated prior to the solubility measurements being undertaken. The solubility of racemic ibuprofen in supercritical CO2 was measured using a dynamic apparatus at pressures between 80 and 220 bar and temperatures of 35, 40, and 45 °C. The solubility data was modeled using the Peng−Robinson equation of state with van der Waals mixing rules. The ratio of R and S isomers in the extract was found to be the same as that in the original material. The solubility of pure optical isomers of ibuprofen, namely, (S)-ibuprofen and (R)-ibuprofen, were also determined at 35 °C within the pressure range of 80−200 bar. It was found that (S)-ibuprofen exhibited solubility in CO2 similar to (R)-ibuprofen, and the solubility of the pure isomers was at least 60% higher than that of the racemic ibuprofen at all pressures. The RESS experiments involved studying the effect of spraying distance, the pre-expansion pressure, and nozzle length on the particle size. The median particle size of ibuprofen precipitated by RESS was less than 2.5 μm. Although the particles obtained were aggregated, they were easily dispersed by ultrasonication in water. The pre-expansion pressure and nozzle length had no effect on the particle size and morphology within the range of operating conditions studied. An increase in spraying distance resulted in a slight decrease in particle size and degree of aggregation. The powder dissolution rate of racemic ibuprofen was enhanced as the particle size decreased. The degree of crystallinity of the processed ibuprofen was slightly decreased; as a result, the micronized product exhibited a higher disk intrinsic dissolution rate. The increase in dissolution rate of ibuprofen was hence due to both the reduction in particle size and the degree of crystallinity.
Interaction between interferon γ and insulin‐like growth factor‐1 in hippocampus impacts on the ability of rats to sustain long‐term potentiation (2006)

There is compelling evidence to suggest that inflammation significantly contributes to neurodegenerative changes. Consistent with this is the observation that several neurodegenerative disorders are accompanied by an increase in the concentration of interleukin (IL)-1beta. IL-1beta has a negative impact on synaptic plasticity and therefore an increased concentration of IL-1beta, such as that in the hippocampus of the aged rat, is associated with a deficit in long-term potentiation (LTP). IL-1beta is derived mainly from activated microglia but the trigger leading to this activation, specifically in the aged brain, remains to be identified. Here we examined the possibility that interferon (IFN)gamma may stimulate microglial activation and increase IL-1beta concentration, thereby inhibiting LTP. The IFNgamma concentration was increased in hippocampus prepared from aged, compared with young, rats and inversely correlated with the ability of rats to sustain LTP. Intracerebroventricular injection of IFNgamma inhibited LTP, and increased microglial activation was observed in both IFNgamma-injected and aged rats. The age-related increase in IFNgamma was accompanied by a decrease in the hippocampal concentration of insulin-like growth factor (IGF)-1. The evidence presented suggests that IGF-1 acts to antagonize the IFNgamma-induced microglial activation, the accompanying increase in IL-1beta concentration and the consequent deficit in LTP.
Light-Driven Formation and Rupture of Droplet Bilayers (2010)

We demonstrate the optical manipulation of nanoliter aqueous droplets containing surfactant or lipid molecules and immersed in an organic liquid using near-infrared light. The resulting emulsion droplets are manipulated using both the thermocapillary effect and convective fluid motion. Droplet-pair interactions induced in the emulsion upon optical initiation and control provide direct observations of the coalescence steps in intricate detail. Droplet-droplet adhesion (bilayer formation) is observed under several conditions. Selective bilayer rupture is also realized using the same infrared laser. The technique provides a novel approach to studying thin film drainage and interface stability in emulsion dynamics. The formation of stable lipid bilayers at the adhesion interface between interacting water droplets can provide an optical platform on which to build droplet-based lipid bilayer assays. The technique also has relevance to understanding and improving microfluidics applications by devising Petri dish-based droplet assays requiring no substrate fabrication.
Estimate of the safe starting dose in clinical trials for therapeutics in adult healthy volunteers (2005)

A strategy was proposed to determine the maximum recommended starting dose (MRSD). Usually, no observe adverse effect level (NOAEL) from the relevant animal studies should be converted to the human equivalent dose (HED) using standard factors. Using sound scientific judgments, the MRSD is determined by dividing the HED from the most appropriate species by the safety factor. This strategy pertained to determining the MRSD of any new drug or biological therapeutic that had been studied in animals, but was not pertinent to prophylactic vaccines or endogenous proteins used at physiologic concentrations.
Characterization of Mammalian Stanniocalcin Receptors (2002)

The polypeptide hormone stanniocalcin (STC) is widely expressed in mammalian tissues. STC acts locally in kidney and gut to modulate calcium and phosphate excretion, and its overexpression in mice results in high serum phosphate, dwarfism, and increased metabolic rate. STC has also been linked to cancer, pregnancy, lactation, angiogenesis, organogenesis, cerebral ischemia, and hypertonic stress. In this report we have characterized the STC receptor and the functional targeting of ligand and receptor to mitochondria. For receptor binding analysis, a stanniocalcin-alkaline phosphatase fusion protein was engineered. Subsequent binding assays using the fusion protein indicated that kidney and liver contained the highest number of binding sites with affinities of 0.8 and 0.25 nm, respectively. Intriguingly, purified mitochondria from both tissues yielded similar high affinity binding sites. Fractionation analysis revealed that the majority of binding sites were localized to the inner mitochondrial membrane. In further studies, we characterized the time course of STC-alkaline phosphatase fusion protein sequestration by intact mitochondria. In situ ligand binding also revealed discrete, displaceable binding to plasma membranes and mitochondria of nephron cells and liver hepatocytes. The existence of mitochondrial receptors prompted a similar search for the ligand. Immunogold electron microscopy revealed that STC was preferentially concentrated in the mitochondria of all nephron segments targeted by STC. Subcellular fractionation revealed that >90% of cellular STC immunoreactivity was mitochondrial, confined to the inner matrix, and similar in size to recombinant STC (50 kDa). In functional studies, recombinant STC had concentration-dependent stimulatory effects on electron transfer by sub-mitochondrial particles. Collectively the evidence implies a role for STC in cell metabolism.