gebhart/patrepeval huggingface dataset:
Neurodegeneration caused by ER stress? (2004)

Mutations of the Parkin gene are responsible for autosomal recessive juvenile parkinsonism (AR-JP), the most common cause of early-onset familial Parkinson's disease. Parkin functions as an E3 ubiquitin ligase, thereby promoting ubiquitination and subsequent proteosomal degradation of its substrate(s). AR-JP is, therefore, thought to be caused by accumulation of an unknown toxic protein(s), which would normally be degraded by a molecular machinery involving Parkin. To date, ten different proteins are reported to be substrates of Parkin. Among these, a G protein-coupled orphan receptor called the Pael receptor (Pael-R), which is highly expressed in dopaminergic neurons, attracts particular attention. When over-expressed in cells, the Pael-R protein became improperly folded and insoluble. Excessive accumulation of insoluble Pael-R led to endoplasmic reticulum (ER) stress-induced cell death. Parkin was observed to ubiquitinate the misfolded Pael-R protein, thereby promoting its degradation and suppressing misfolded Pael-R-induced cell death. Moreover, selective dopaminergic neurodegeneration was observed when human Pael-R was ectopically expressed in Drosophila brain, further supporting the idea that Pael-R accumulation plays a major role in AR-JP. In contrast, neither dopaminergic neurodegeneration nor accumulation of any known Parkin substrates was detected in Parkin knockout mice. The role of Pael-R in AR-JP will be discussed based on recent data.
Comparison of the Superagonist Complex, ALT-803, to IL15 as Cancer Immunotherapeutics in Animal Models (2015)

IL15, a potent stimulant of CD8(+) T cells and natural killer (NK) cells, is a promising cancer immunotherapeutic. ALT-803 is a complex of an IL15 superagonist mutant and a dimeric IL15 receptor αSu/Fc fusion protein that was found to exhibit enhanced biologic activity in vivo, with a substantially longer serum half-life than recombinant IL15. A single intravenous dose of ALT-803, but not IL15, eliminated well-established tumors and prolonged survival of mice bearing multiple myeloma. In this study, we extended these findings to demonstrate the superior antitumor activity of ALT-803 over IL15 in mice bearing subcutaneous B16F10 melanoma tumors and CT26 colon carcinoma metastases. Tissue biodistribution studies in mice also showed much greater retention of ALT-803 in the lymphoid organs compared with IL15, consistent with its highly potent immunostimulatory and antitumor activities in vivo. Weekly dosing with 1 mg/kg ALT-803 in C57BL/6 mice was well tolerated, yet capable of increasing peripheral blood lymphocyte, neutrophil, and monocyte counts by >8-fold. ALT-803 dose-dependent stimulation of immune cell infiltration into the lymphoid organs was also observed. Similarly, cynomolgus monkeys treated weekly with ALT-803 showed dose-dependent increases of peripheral blood lymphocyte counts, including NK, CD4(+), and CD8(+) memory T-cell subsets. In vitro studies demonstrated ALT-803-mediated stimulation of mouse and human immune cell proliferation and IFNγ production without inducing a broad-based release of other proinflammatory cytokines (i.e., cytokine storm). Based on these results, a weekly dosing regimen of ALT-803 has been implemented in multiple clinical studies to evaluate the dose required for effective immune cell stimulation in humans.
Modified horner–emmons reaction of polymeric phosphonates: Versatile synthesis of pendant stilbene‐containing polymers (1995)

Abstract Poly[styrene‐ co ‐(diethyl vinylbenzylphosphonate)] and poly[methylmethacrylate‐ co ‐(diethyl vinylbenzylphosphonate)] were prepared and used in modified Horner‐Emmons reactions to synthesize polymers with covalently attached stilbene groups. This versatile new method allowed for the preparation of polymers with either electron‐donor (OCH 3 , CH 3 ) or electron acceptor (Br, NO 2 ) substituents on the stilbene aromatic ring. The resulting polymers were characterized by 1 H NMR, FT‐IR, UV‐visible, DSC, and size exclusion chromatography. Efficient transformation of polymeric phosphonates to the polymeric stilbene derivatives was realized. Size exclusion chromatographic analyses demonstrated that the reaction conditions have no deleterious effect on the molecular weight distribution of the various polymers that were prepared. Photochromic behavior was demonstrated for one of the derivatives. © 1995 John Wiley &amp; Sons, Inc.
Bacterial degradation of N-cyclopropylmelamine. The steps to ring cleavage (1984)

The s-triazine cyclopropylmelamine (N-cyclopropyl-1,3,5-triazine-2,4,6-triamine) was degraded to about 6 mol of NH4+/mol of substrate by a mixture of two bacteria (strains A and D, both Pseudomonas spp.) Only strain A grew with cyclopropylmelamine as sole and limiting source of nitrogen. The organism obtained 2 mol of nitrogen/mol of substrate and excreted a product that was identified as cyclopropylammelide [6-cyclopropylamino-1,3,5-triazine-2,4(1 H,3 H)-dione]. Proteins in extracts from strain A were separated on a Sephadex G-200 column. Cyclopropylmelamine was found to be deaminated in two separable steps to cyclopropylammelide via cyclopropylammeline [4-amino-6-cyclopropylamino-1,3,5-triazine-2(1 H)-one], which was identified. Strain D could not utilize cyclopropylmelamine or cyclopropylammeline, but could utilize cyclopropylammelide (or homologue) as sole and limiting source of nitrogen and obtain about 4 mol of nitrogen/mol of substrate. Proteins in cell extracts from strain D were separated on a DEAE-cellulose column. Alkylammelides were degraded quantitatively by one enzyme fraction to 1 mol of cyanuric acid plus 1 mol of alkylamine/mol of substrate. The specific activities of enzymes in extracts of the two strains were as high as the activities observed during growth. The three activities studied in the two strains were all active under aerobic and oxygen-free conditions. The reactions appear to be hydrolytic, yielding 2 mol of NH4+ plus 1 mol of cyclopropylamine and 1 mol of cyanuric acid/mol of substrate.
Effect of Ramipril, an Inhibitor of Angiotensin Converting Enzyme, on the Response of Rat Thoracic Aorta to Injury with a Balloon Catheter (1991)

We have studied the effect of ramipril (10 mg/kg daily by gastric gavage) on the development of neointima 2 and 14 days after injury to rat aorta with a balloon catheter. In treated animals, there was no significant inhibition of the early mitotic reaction after injury (synthesis of DNA, as reflected by aortic thymidine incorporation on the second day): the mean (95% confidence interval) was 3,553 (892) in the control group vs. 2,853 disintegrations/min/micrograms of DNA (555) in the treated group, 2 p greater than 0.15. However, ramipril decreased the amount of neointima formed 14 days after injury, as characterized by (a) a highly significant decrease of the intima to intima + media areas ratio [21.1 (2.4) vs. 13.7% (2.2), 2 p less than 10(-4]); (b) a significant decrease of intima-media wet weight [35.4 (1.0) vs. 30.9 mg (0.9), 2p less than 0.005]; and (c) without any significant effect on intima-media DNA content [96.3 (7.9) vs. 91.7 micrograms (5.7), 2p greater than 0.3]. These observations suggest that angiotensin converting enzyme inhibitors may not act mainly through an inhibition of smooth muscle cell proliferation. Other effects, such as inhibition of migration, hypertrophy, and matrix synthesis, should also be considered.
J for the APL programmer (1996)

Though J shares many concepts with APL, in many respects it is radically different, and almost all APL constructions that are in J differ in some way. These differences can be a stumbling block to the newcomer who thinks that J is simply an ASCII version of APL, prompting questions such as:• How do I save my workspace?• Why do J functions work along the columns and not the rows?• Can I have a version of J with □ io ←1?• Can I have a version of J with real APL characters?
Temporally coherent local tone mapping of HDR video (2014)

Recent subjective studies showed that current tone mapping operators either produce disturbing temporal artifacts, or are limited in their local contrast reproduction capability. We address both of these issues and present an HDR video tone mapping operator that can greatly reduce the input dynamic range, while at the same time preserving scene details without causing significant visual artifacts. To achieve this, we revisit the commonly used spatial base-detail layer decomposition and extend it to the temporal domain . We achieve high quality spatiotemporal edge-aware filtering efficiently by using a mathematically justified iterative approach that approximates a global solution. Comparison with the state-of-the-art, both qualitatively, and quantitatively through a controlled subjective experiment, clearly shows our method's advantages over previous work. We present local tone mapping results on challenging high resolution scenes with complex motion and varying illumination. We also demonstrate our method's capability of preserving scene details at user adjustable scales, and its advantages for low light video sequences with significant camera noise.
Molecular Dynamics Simulation To Investigate Differences in Minor Groove Hydration of HNA/RNA Hybrids As Compared to HNA/DNA Complexes (1998)

Hexitol nucleic acids (HNA) are oligonucleotides built up from natural nucleobases and a phosphorylated 1,5-anhydrohexitol backbone. Molecular associations between HNA and RNA are more stable than between HNA and DNA and between natural nucleic acids (dsDNA, dsRNA, DNA/RNA). 1H NMR analysis of a HNA dimer confirms the axial orientation of the base moiety with respect to the hexitol ring, and this was used as starting conformation for a molecular dynamics study of HNA/RNA and HNA/DNA duplexes. Both complexes show an A-type geometry and very similar hydrogen bonding patterns between base pairs. The relative stability of HNA/RNA versus HNA/DNA might be explained by a difference in minor groove solvatation.
Effect of Food on Acetaminophen Absorption in Young and Elderly Subjects (1982)

Twenty-four healthy volunteers aged 22 to 78 years received 650-mg doses of acetaminophen (AAP) on five separate occasions. The modes of administration were: intravenous AAP by 5-minute infusion; oral AAP as two 325-mg tablets in the fasting state; oral AAP 650 mg as an elixir preparation in the fasting state; tablets with food; and elixir with food. Plasma concentrations of AAP were determined by high-pressure liquid chromatography for up to 12 hours after the dose. In both the young and the elderly groups, the four oral modes of administration were significantly different with respect to peak plasma concentration (P less than 0.001), time to peak plasma concentration (P less than 0.001), and systemic availability (P less than 0.01). Although food slowed the rate of absorption of both oral preparations, no significant difference in peak acetaminophen plasma concentration or time of peak concentration was observed as a function of age. Absolute systemic availability of elixir and tablets in the fasting state tended to be lower in the elderly subjects (P less than 0.05). However, when either preparation was coadministered with food, there were no differences between the two age groups. Thus, age as such does not appear to be a critical determinant in the design of oral acetaminophen dosage schedules.
Plasmid segregation into minicells is associated with membrane attachment and independent of plasmid replication (1986)

The role of plasmid replication in the segregation of plasmids into Escherichia coli minicells was investigated with temperature-sensitive replication mutants derived from E. coli plasmids ColE1 and pSC101. For as long as six generations of growth, at permissive or nonpermissive temperatures (when greater than 80% of plasmid replication was inhibited), the same amount of previously 3H-labeled plasmid DNA segregated into minicells. Density gradient separations of wild-type and temperature-sensitive plasmid DNA from both replicons segregated into the minicells showed that about 20 to 25% was stably associated with the minicell membrane at both temperatures. Electron microscopy showed this DNA to consist of circular plasmid molecules attached to the minicell membrane. These combined findings suggest that segregation of plasmids into minicells and their association with the minicell membrane are interrelated and independent of plasmid replication.
MEANDERING NANOCHANNELS FOR IMAGING OF ULTRA-LONG DNA MOLECULES (2011)

A new chip design for handling and studying chromosomal DNA is described. Folding the nanochannels enables us to image an entire yeast chromosome in a single field of view. Together with existing mapping techniques our new design opens up the possibility of directly analyzing entire chromosomes in a single field of view using fluorescence microscopy. This would enable, for example, identification of microorganisms on a single-cell basis and the complete physical mapping of the human genome, chromosome by chromosome.
Repellents Inhibit P450 Enzymes in Stegomyia (Aedes) aegypti (2012)

The primary defence against mosquitoes and other disease vectors is often the application of a repellent. Despite their common use, the mechanism(s) underlying the activity of repellents is not fully understood, with even the mode of action of DEET having been reported to be via different mechanisms; e.g. interference with olfactory receptor neurones or actively detected by olfactory receptor neurones on the antennae or maxillary palps. In this study, we discuss a novel mechanism for repellence, one of P450 inhibition. Thirteen essential oil extracts from Colombian plants were assayed for potency as P450 inhibitors, using a kinetic fluorometric assay, and for repellency using a modified World Health Organisation Pesticide Evaluations Scheme (WHOPES) arm-in cage assay with Stegomyia (Aedes) aegypti mosquitoes. Bootstrap analysis on the inhibition analysis revealed a significant correlation between P450-inhibition and repellent activity of the oils.
Active immunotherapy of tumors with a recombinant xenogeneic endoglin as a model antigen (2004)

Angiogenesis play a critical role in tumor growth and metastasis. Increasing evidence suggests that endoglin is a powerful marker of angiogenesis in solid malignancies. Thus, breaking of immune tolerance of self-endoglin-associated angiogenesis is an attractive approach to cancer therapy. To test this concept, we recombined the extracellular domains of porcine endoglin, and used it as a xenogeneic vaccine. We found that immunotherapy with porcine endoglin was effective at both protective and therapeutic anti-tumor immunity in several mouse tumor models. Autoantibodies against mouse endoglin were identified by Western blot and ELISA. IgG1 and IgG2b were substantially increased. Anti-endoglin antibody-producing B cells were detectable by ELISPOT assay. There was endothelial deposition of immunoglobulins within tumors. The anti-tumor activity was also induced by the adoptive transfer of the purified immunoglobulins. Angiogenesis was apparently inhibited within the tumor tissues and on the alginate beads. The increased apoptotic cells were found within the tumor tissues from the mice treated with porcine endoglin. The anti-tumor activity and production of autoantibodies against mouse endoglin could be abrogated by depletion of CD4(+) T lymphocytes. Remarkably, no marked toxicity was found in the immunized mice. These observations may provide an alternative rational strategy for active cancer immunotherapy.
Internalization and down-regulation of the human epidermal growth factor receptor are regulated by the carboxyl-terminal tyrosines (1991)

The C terminus of the epidermal growth factor receptor (EGF-R) contains three tyrosines (Y1068, Y1148, and Y1173) which correspond to the major autophosphorylation sites. To investigate the role of the tyrosines in internalization and down-regulation of the EGF-R, mutational analysis was performed with receptors in which 1, 2, or all 3 tyrosines were changed to phenylalanines. The triple point mutant EGF-R, expressed in NIH-3T3, exhibited low autophosphorylation in vivo, low biological and reduced kinase activities. Single and double point mutants were down-regulated, as well as wild type EGF-R in response to EGF showing a half-life of about 1 h. Degradation of the triple point mutant, however, was impaired and resulted in a half-life of 4 h in the presence of EGF. EGF-dependent down-regulation of surface receptors was decreased in the triple point mutant EGF-R as was internalization and degradation of EGF. The specific rate of internalization of the triple point mutant was reduced. By contrast, intracellular processing of ligand previously internalized at 20 degrees C was similar between wild type and mutant receptors. Taken together the data indicate that the delay in degradation observed in cells expressing the triple point mutant EGF-R can be attributed mainly to a slower removal from the cell surface. Our results show that in the full-length EGF-R all three C-terminal tyrosines are necessary for rapid internalization, suggesting that autophosphorylation is required for efficient EGF-dependent receptor endocytosis.
heat in history Isaac Newton and Heat Transfer (1998)

Abstract An attempt is made to provide historical perspectives on the influences of Newton's law of cooling (1701) on the development of heat transfer theory. Newton's cooling law provides the first heat transfer formulation and is the formal basis of convective heat transfer. The cooling law was incorporated by Fourier (1822) as the convective boundary condition (Biot number) in his mathematical theory of heat conduction. The decisive step in the application of the concept of heat transfer coefficient occurred with the publication of the "basic law of heat transfer" by Nusselt in 1915. Newton's law is valid only for forced convection with constant physical properties. The close relationships for various heat transfer theories are pointed out. Heat transfer phenomena can also be classified based on the relationship between surface heat flux and temperature difference as a driving force.
New Hyaluronic Acid Filler for Subdermal and Long-lasting Volume Restoration of the Face (2009)

Over the past few years, the focus in the field of aesthetic medicine has gradually shifted towards minimally invasive procedures. As more and more patients are refusing to take prolonged absences from their work, the use of filler materials, botulinum toxin A, peelings, laser, fat implantation and other minor surgical corrections has significantly increased. Minimally invasive volume restoration of the face through long-lasting resorbable fillers is nowadays more attractive and important to patients.
Reduced Wound Contraction After Grafting of Full-Thickness Burns with a Collagen and Chondroitin-6-Sulfate (GAG) Dermal Skin Substitute and Coverage with Biobrane (1988)

Full-thickness burns destroy both the epidermal and dermal tissues of the skin. This study evaluates a collagen and chondroitin-6-sulfate dermal skin substitute (graft) that was applied to excised full-thickness burns and covered with Biobrane. Experimental conditions included: (a) no burn, subcutaneous implantation of the graft; (b) burn, excision, graft, coverage with Biobrane and bandages; (c) burn, excision, no graft, coverage with Biobrane and bandages; (d) burn only. forty-one days post-surgery, subcutaneous implantation (N = 3) of the graft caused no detectable contraction or necrosis of the overlying skin, whereas all burn wounds contracted. Measurements of wounds (percentage of original wound size) showed statistically significant differences between the following treatments; (a) graft plus Biobrane (N = 10), 34%; (b) no graft plus Biobrane (N = 9), 25%; (c) untreated burns (N = 6), 16%. Semi-quantitative evaluation of time to healing indicated by spontaneous detachment of Biobrane from wounds showed that grafted, excised wounds healed in an average of 2.7 weeks, while ungrafted, excised wounds required an average of 4.3 weeks to heal. Histological appearance of healed wounds after grafting and coverage with Biobrane resembles undamaged skin without epidermal adnexal structures. Excision of full-thickness burn eschar, followed by grafting with a collagen and chondroitin-6-sulfate dermal skin substitute and coverage with Biobrane provides reduced wound contraction within a six-week period of observation compared to non-excised wounds. Both more rapid and more complete wound healing took place compared to excised wounds that were not grafted.
Time, clocks, and the ordering of events in a distributed system (1978)

The concept of one event happening before another in a distributed system is examined, and is shown to define a partial ordering of the events. A distributed algorithm is given for synchronizing a system of logical clocks which can be used to totally order the events. The use of the total ordering is illustrated with a method for solving synchronization problems. The algorithm is then specialized for synchronizing physical clocks, and a bound is derived on how far out of synchrony the clocks can become.
Structure, expression, and functional analysis of a Na(+)-dependent glutamate/aspartate transporter from rat brain. (1992)

Transport systems specific for L-glutamate and L-aspartate play an important role in the termination of neurotransmitter signals at excitatory synapses. We describe here the structure and function of a 66-kDa glycoprotein that was purified from rat brain and identified as an L-glutamate/L-aspartate transporter (GLAST). A GLAST-specific cDNA clone was isolated from a rat brain cDNA library. The cDNA insert encodes a polypeptide with 543 amino acid residues (59,697 Da). The amino acid sequence of GLAST suggests a distinctive structure and membrane topology, with some conserved motifs also present in prokaryotic glutamate transporters. The transporter function has been verified by amino acid uptake studies in the Xenopus laevis oocyte system. GLAST is specific for L-glutamate and L-aspartate, shows strict dependence on Na+ ions, and is inhibited by DL-threo-3-hydroxy-aspartate. In situ hybridization reveals a strikingly high density of GLAST mRNA in the Purkinje cell layer of cerebellum, presumably in the Bergmann glia cells, and a less dense distribution throughout the cerebrum. These data suggest that GLAST may be involved in the regulation of neurotransmitter concentration in central nervous system.
Camera calibration using time-coded planar patterns (2012)

In this paper a novel pattern design for camera calibration using planar patterns with the Zhang calibration method is presented. In contrast to other work related to this calibration technique, which deals with the design and extraction of spatial image features, our focus lies on the precise and fully automated extraction of corresponding points by temporal image features using a sequence of planar patterns, which are displayed by a flat screen. The extraction of correspondences in our approach does not utilize areal properties of the images and therefore is hardly influenced by projective distortion, image distortion, or inhomogeneous illumination. Furthermore, not the whole pattern but only parts of it need to be visible in an individual view. In addition, the planarity as well as the physical precision of the control points of the pattern are ensured by the very nature of the flat screen. The overall calibration time may be reduced, as no human interaction is necessary. We compare the results gained from this novel temporal pattern design with those gained from commonly used checkerboard patterns. The proposed approach resulted in an increased precision for the calibration.