gebhart/patrepeval huggingface dataset:
Enhanced antitumor activity of combination radioimmunotherapy (131I-labeled monoclonal antibody A33) with chemotherapy (fluorouracil). (1997)

Monoclonal antibody (mAb) A33 reacts with an antigen expressed by >95% of colon cancer and normal colon epithelial cells. An earlier Phase I trial of 131I-labeled mAb A33 (131I-mAb A33) demonstrated bone marrow suppression as the dose-limiting toxicity, and although modest antitumor effects were seen, no normal colon toxicity was observed. In this study, a nude mouse model was used to test whether combinations of low-dose 131I-mAb A33 (0.1 mCi) and chemotherapy [5-fluorouracil (5-FU) or 5-FU + leucovorin, doxorubicin, or carmustine] enhance the antitumor effects, compared to 131I-mAb A33 alone or either drug regimen alone. 5-FU was administered either at 30 mg/kg/day for 5 days or at 75 mg/kg/day on days 1 and 5. In assessing the reduction in tumor volumes over the first 28 days of the experiment, 5-FU treatment (with or without leucovorin) in combination with 131I-mAb A33 showed a statistically significant additive antitumor effect compared to 131I-mAb A33 alone or to chemotherapy alone. When long-term survival was used as an end point, 38% of the mice treated with 5-FU and 131I-mAb A33 were disease free at 276 days compared to none from any other group, suggesting a synergistic effect. These data indicate that Phase II clinical trials combining radiolabeled antibody therapy with 5-FU-based treatments are warranted.
Bruch's membrane and choroidal macrophages in early and advanced age-related macular degeneration (2009)

The presence of extracellular deposits (soft drusen and thick continuous basal laminar deposit) is associated with macrophage recruitment to BrM and alteration in the immunophenotype of resident choroidal macrophages.
Keypoint recognition using randomized trees (2006)

In many 3D object-detection and pose-estimation problems, runtime performance is of critical importance. However, there usually is time to train the system, which we will show to be very useful. Assuming that several registered images of the target object are available, we developed a keypoint-based approach that is effective in this context by formulating wide-baseline matching of keypoints extracted from the input images to those found in the model images as a classification problem. This shifts much of the computational burden to a training phase, without sacrificing recognition performance. As a result, the resulting algorithm is robust, accurate, and fast-enough for frame-rate performance. This reduction in runtime computational complexity is our first contribution. Our second contribution is to show that, in this context, a simple and fast keypoint detector suffices to support detection and tracking even under large perspective and scale variations. While earlier methods require a detector that can be expected to produce very repeatable results, in general, which usually is very time-consuming, we simply find the most repeatable object keypoints for the specific target object during the training phase. We have incorporated these ideas into a real-time system that detects planar, nonplanar, and deformable objects. It then estimates the pose of the rigid ones and the deformations of the others.
Transmission of Creutzfeldt-Jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein. (1994)

Transgenic (Tg) mice were constructed that express a chimeric prion protein (PrP) in which a segment of mouse (Mo) PrP was replaced with the corresponding human (Hu) PrP sequence. The chimeric PrP, designated MHu2MPrP, differs from MoPrP by 9 amino acids between residues 96 and 167. All of the Tg(MHu2M) mice developed neurologic disease approximately 200 days after inoculation with brain homogenates from three patients dying of Creutzfeldt-Jakob disease (CJD). Inoculation of Tg(MHu2M) mice with CJD prions produced MHu2MPrPSc (where PrPSc is the scrapie isoform of PrP); inoculation with Mo prions produced Mo-PrPSc. The patterns of MHu2MPrPSc and MoPrPSc accumulation in the brains of Tg(MHu2M) mice were different. About 10% of Tg(HuPrP) mice expressing HuPrP and non-Tg mice developed neurologic disease > 500 days after inoculation with CJD prions. The different susceptibilities of Tg(HuPrP) and Tg(MHu2M) mice to Hu prions indicate that additional species-specific factors are involved in prion replication. Diagnosis, prevention, and treatment of Hu prion diseases should be facilitated by Tg(MHu2M) mice.
Como atraer y retener docentes calificados en la Argentina : impacto del nivel y la estructura de la remuneracion (1999)

The study outlines current conflicting issues regarding teacher salaries in Argentina, and argues on how to attract, and retain qualified teachers, by initially comparing teacher salaries, to those of workers in different occupational fields, questioning whether within the Argentine labor market, teachers are better off than workers at equal levels, i.e., gender, age, and educational level wise. Within the general educational structure, gradual changes in teacher salaries are described to form the basis for analysis. Discussions suggest that, salary raises at the national level, including specific policies on teacher salaries, may not be the best practice to attract skillful teachers, rather salary adjustments at the provincial level, could reflect the particular requirement needs per region, potentially attracting highly qualified staff, who may be interested and experienced in sharing their specific knowledge, building a more alluring teaching capacity. Nonetheless, the study does suggest the need to change teacher salary structures, by rewarding teacher experience, in order to retain those mostly qualified, who may in turn motivate changes in educational components, or in teacher training, and responsiveness, as needed. Recommendations also include innovations, such as granting individual bonuses to influence professional excellence.
Polysaccharides from Eukaryotes (2002)

Pullulan (T. Leathers). Scleroglucan (I. Giavasis, et al.). Schizophyllan (U. Rau). Yeast Extracellular Polysaccharides (S. De Baets, et al.). Chitin and Chitosan in Fungi (M. Peter). Fungal Cell Wall Glycans (S. C. Jong). Agar Cell Wall beta Glucans of Saccharomyces cerevisiae (G. Dijkgraaf, et al.). Alginates from Algae (K. Draget, et al.). Carrageenan (F. de Velde, et al.). Cellulose (D. Klemm, et al.). Seed Gums (S. Dierckx & K. Dewettinck). Pectins (M. C. Ralet, et al.). Starch (R. Tester & J. Karkalas). Inulin (A. Franck & L. De Leenheer). Chitin and Chitosan from Animal Sources (M. Peter). Proteoglycans (Glycosaminoglycans/Mucopolysaccharides) (T. Nakano, et al.). Index.
Effect of Vagotomy and Vagal Stimulation on Insulin Secretion (1967)

The influence of the vagus nerve on insulin secretion in the dog has been confirmed by studies involving both vagotomy and vagal stimulation. Following vagotomy, a fall in portal vein insulin levels occurs. Following stimulation of both the right and left vagus, insulin levels rise abruptly, peak within five minutes and rapidly return to baseline levels. A small rise in blood glucose, which occurs simultaneously, cannot be blocked by phentolamine, an alpha-adrenergic blocking agent. When given alone, phentolamine stimulates insulin secretion. Atropine inhibits both the glucose and insulin rises following vagal stimulation. Only a portion of releasable insulin appears to be under vagal control. Glucose mediated insulin release and net glucose utilization are not significantly affected by vagotomy.
The inhibition of nitric oxide-activated poly(ADP-ribose) synthetase attenuates transsynaptic alteration of spinal cord dorsal horn neurons and neuropathic pain in the rat (1997)

Transsynaptic alteration of spinal cord dorsal horn neurons characterized by hyperchromatosis of cytoplasm and nucleoplasm (so-called 'dark' neurons) occurs in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the common sciatic nerve. The incidence of dark neurons in CCI rats has been proposed to be mediated by glutamate-induced neurotoxicity. In the present study, we examined whether the inhibition of the nitric oxide (NO)-activated poly(ADP-ribose) synthetase (PARS), a nuclear enzyme critical to glutamate-induced neurotoxicity, would both reduce the incidence of dark neurons and attenuate behavioral manifestations of neuropathic pain in CCI rats. Dark neurons were observed bilaterally (with ipsilateral predominance) within the spinal cord dorsal horn, particularly in laminae I-II, of rats 8 days after unilateral sciatic nerve ligation as compared to sham operated rats. The number of dark neurons in the dorsal horn was dose-dependently reduced in CCI rats receiving once daily intrathecal (i.t.) treatment with the PARS inhibitor benzamide (200 or 400 nmol, but not 100 nmol benzamide or saline) for 7 days. Consistent with the histological improvement, thermal hyperalgesia, mechanical hyperalgesia, and low threshold mechano-allodynia also were reliably reduced in CCI rats treated with either 200 or 400 nmol benzamide. Neither dark neurons nor neuropathic pain behaviors were reliably affected by i.t. administration of either 800 nmol novobiocin (a mono(ADP-ribose) synthetase) or 800 nmol benzoic acid (the backbone structure of benzamide), indicating a selective effect of benzamide. Intrathecal treatment with an NO synthase inhibitor NG-nitro-L-arginine methyl ester (40 nmol, but not its inactive D-isomer) utilizing the same benzamide treatment regimen resulted in similar reductions of both dark neurons and neuropathic pain behaviors in CCI rats. These results provide, for the first time, in vivo evidence indicating that benzamide is neuroprotective and that the PARS-mediated transsynaptic alteration of spinal cord dorsal horn neurons contributes to behavioral manifestations of neuropathic pain in CCI rats. These observations may have general implications beyond treatment of neuropathic pain in that PARS-mediated neuronal alterations may play a significant role in glutamate-mediated neurotoxicity under many other circumstances.
Relaxin Secretion into Human Semen is Independent of Gonadotropin Stimulation1 (1994)

To investigate the control of relaxin (Rlx) secretion in men, we studied seminal plasma Rlx concentrations after physiologic and supraphysiologic gonadal stimulation. In the first experiment, 14 men with idiopathic hypogonadotropic hypogonadism provided semen samples at various time points before and during therapy with pulsatile GnRH. These data were compared to seminal plasma Rlx values in 5 normal men. In a second experiment, pharmacologic doses of hCG were administered in a fashion similar to that previously shown to have stimulated Rlx secretion from the CL of women. In men with idiopathic hypogonadotropic hypogonadism, no relationship was detected by linear regression analysis between seminal plasma Rlx and testosterone, testicular volume, ejaculate volume, or the appearance of sperm in the ejaculate. Rlx concentrations varied considerably between subjects (6-120 ng/ml) but remained fairly consistent within the same individual over time. Supraphysiologic gonadal stimulation with hCG similarly failed to alter seminal plasma Rlx (n = 5, mean +/- SEM; 48 +/- 9 ng/ml, 42 +/- 7 ng/ml, and 56 +/- 9 ng/ml on Days 1, 3, and 6, respectively; p < 0.05) in normal men despite dramatic increases in serum testosterone (763 +/- 25 ng/dl, 1702 +/- 136 ng/dl, and 1494 +/- 97 ng/dl on Days 1, 3, and 6, respectively; p < 0.05 vs. Day 1). Taken together, these data suggest that Rlx in men is secreted independently from direct gonadotropin control.
The BH4 Domain of Anti-apoptotic Bcl-XL, but Not That of the Related Bcl-2, Limits the Voltage-dependent Anion Channel 1 (VDAC1)-mediated Transfer of Pro-apoptotic Ca2+ Signals to Mitochondria (2015)

Excessive Ca(2+) fluxes from the endoplasmic reticulum to the mitochondria result in apoptotic cell death. Bcl-2 and Bcl-XL proteins exert part of their anti-apoptotic function by directly targeting Ca(2+)-transport systems, like the endoplasmic reticulum-localized inositol 1,4,5-trisphosphate receptors (IP3Rs) and the voltage-dependent anion channel 1 (VDAC1) at the outer mitochondrial membranes. We previously demonstrated that the Bcl-2 homology 4 (BH4) domain of Bcl-2 protects against Ca(2+)-dependent apoptosis by binding and inhibiting IP3Rs, although the BH4 domain of Bcl-XL was protective independently of binding IP3Rs. Here, we report that in contrast to the BH4 domain of Bcl-2, the BH4 domain of Bcl-XL binds and inhibits VDAC1. In intact cells, delivery of the BH4-Bcl-XL peptide via electroporation limits agonist-induced mitochondrial Ca(2+) uptake and protects against staurosporine-induced apoptosis, in line with the results obtained with VDAC1(-/-) cells. Moreover, the delivery of the N-terminal domain of VDAC1 as a synthetic peptide (VDAC1-NP) abolishes the ability of BH4-Bcl-XL to suppress mitochondrial Ca(2+) uptake and to protect against apoptosis. Importantly, VDAC1-NP did not affect the ability of BH4-Bcl-2 to suppress agonist-induced Ca(2+) release in the cytosol or to prevent apoptosis, as done instead by an IP3R-derived peptide. In conclusion, our data indicate that the BH4 domain of Bcl-XL, but not that of Bcl-2, selectively targets VDAC1 and inhibits apoptosis by decreasing VDAC1-mediated Ca(2+) uptake into the mitochondria.
An electrically small antenna concept design for transmitting a baseband signal (2017)

Based on the stored energy manipulation, an Electrically Small Antenna concept design, capable of transmitting a high data rate signal is introduced. The design concept allows transmitting a monocycle or a half cycle sinusoid as “1” and no signal as “0”. A simple circuit model is employed to demonstrate the technique and then a hybrid simulation (full wave + transient analysis) is used to investigate the proposed method for a Very Low Frequency underwater communication link.
Enzyme‐catalyzed synthesis of sugar‐containing monomers and linear polymers (2000)

Commercially available proteases and lipases were screened for their ability to acylate regioselectively sucrose and trehalose with divinyladipic acid ester. Opticlean M375 (subtilisin from Bacillus licheniformis) was observed to form sucrose 1′-O-adipate and trehalose 6-O-adipate in anhydrous pyridine. Novozym-435 (lipase B from Candida antarctica) catalyzed the synthesis of sucrose 6, 6′-O-divinyladipate and trehalose 6, 6′-O-divinyladipate in acetone. These diesters were then employed as monomers in polycondensation reactions with various diols (aliphatic and aromatic) catalyzed by Novozym-435 in organic solvents to yield linear polyesters with Mw's up to 22,000 Da. Spectroscopic analysis confirmed that only the vinyl end groups of sugar esters reacted in the enzymatic polymerization with the diol, and not the internal sugar-adipate linkages. The two-step enzymatic strategy to yield sugar-based polyesters, which is the first report of its kind, results in higher molecular weights and faster reaction times than one-step enzymatic polyester synthesis. © 2000 John Wiley & Sons, Inc. Biotechnol Bioeng 70: 208–216, 2000.
Analysis of Putative Heparin-binding Domains of Fibroblast Growth Factor-1 (1995)

The contribution of individual basic amino acids within three putative "consensus sequences" for heparin binding of fibroblast growth factor-1 have been examined by site-directed mutagenesis. The results indicate that a significant reduction in the apparent affinity of fibroblast growth factor-1 for heparin is only observed when basic residues in one of the three regions are mutated. Mutation in the other regions are without affect on heparin binding. The heparin binding properties of synthetic peptides based on the three "consensus sequences" paralleled the mutagenesis results. That is, synthetic peptides corresponding to regions of the protein that were affected by mutagenesis with respect to heparin binding exhibited a relatively high affinity for immobilized heparin, whereas those corresponding to regions of similar charge density that were unaffected by mutagenesis did not. In addition, amino acid substitution of a nonbasic residue in the heparin-binding peptide could abolish its heparin binding capacity. The heparin-binding peptide could antagonize the mitogenic activity of FGF-1, probably because of the heparin dependence of this activity. Together these data demonstrate that the heparin binding properties of fibroblast growth factor-1 are dictated by structural features more complex than clusters of basic amino acids. The results of these and other studies indicate that consensus motifs for heparin-binding require further definition. More importantly, the results provide a basis for the design of peptide-based inhibitors of FGF-1.
Inhibitors of pendrin anion exchange identified in a small molecule screen increase airway surface liquid volume in cystic fibrosis (2016)

Pendrin (SLC26A4) is a Cl(-)/anion exchanger expressed in the epithelium of inflamed airways where it is thought to facilitate Cl(-) absorption and HCO3 (-) secretion. Studies using pendrin knockout mice and airway epithelial cells from hearing-impaired subjects with pendrin loss of function suggest involvement of pendrin in inflammatory lung diseases, including cystic fibrosis (CF), perhaps by regulation of airway surface liquid (ASL) volume. Here we identified small-molecule pendrin inhibitors and demonstrated their efficacy in increasing ASL volume. A cell-based, functional high-throughput screen of ∼36,000 synthetic small molecules produced 3 chemical classes of inhibitors of human pendrin. After structure-activity studies, tetrahydropyrazolopyridine and pyrazolothiophenesulfonamide compounds reversibly inhibited pendrin-facilitated Cl(-) exchange with SCN(-), I(-), NO3 (-), and HCO3 (-) with drug concentration causing 50% inhibition down to ∼2.5 μM. In well-differentiated primary cultures of human airway epithelial cells from non-CF and CF subjects, treatment with IL-13, which causes inflammation with strong pendrin up-regulation, strongly increased Cl(-)/HCO3 (-) exchange and the increase was blocked by pendrin inhibition. Pendrin inhibition significantly increased ASL depth (by ∼8 μm) in IL-13-treated non-CF and CF cells but not in untreated cells. These studies implicate the involvement of pendrin-facilitated Cl(-)/HCO3 (-) in the regulation of ASL volume and suggest the utility of pendrin inhibitors in inflammatory lung diseases, including CF.-Haggie, P. M., Phuan, P.-W., Tan, J.-A., Zlock, L., Finkbeiner, W. E., Verkman, A. S. Inhibitors of pendrin anion exchange identified in a small molecule screen increase airway surface liquid volume in cystic fibrosis.
Internal structural features of E. coli glycyl-tRNA synthetase examined by subunit polypeptide chain fusions. (1986)

In contrast to most aminoacyl-tRNA synthetases which are monomers or oligomers of a single polypeptide, Escherichia coli glycyl-tRNA synthetase has an alpha-2, beta-2 structure. The enzyme requires both subunits for catalysis of either adenylate or aminoacyl-tRNA synthesis. The head-to-tail arrangement of the alpha- and beta-chain coding regions in the genome suggests that the two-subunit protein may be tantamount to a single chain. We fused the carboxyl terminus of the alpha-chain to the amino terminus of the beta-chain, through a short peptide linker. Five different amino acid substitutions were placed in the linker. In all instances, the fusion polypeptide is stable in maxicell extracts. In a glyS null strain, a gene encoding any of the fusion proteins substitutes for the wild-type gene. Assays confirm that, in vitro, the engineered polypeptide fusion is active to within 2- to 3-fold of the wild-type, unfused chains. Oligomers of the fusion protein are observed and may be required for activity. Because the creation and limited manipulation of the artificial peptide linker region does not destroy the activity, we also conclude that the C-terminal part of the alpha-chain and the amino-terminal part of the beta-chain are not important for activity.
Oligomerization of G-protein-coupled Receptors Shown by Selective Co-immunoprecipitation (2002)

Recent studies have shown that G-protein-coupled receptors (GPCRs) can assemble as high molecular weight homo- and hetero-oligomeric complexes. This can result in altered receptor-ligand binding, signaling, or intracellular trafficking. We have co-transfected HEK-293 cells with differentially epitope-tagged GPCRs from different subfamilies and determined whether oligomeric complexes were formed by co-immunoprecipitation and immunoblot analysis. This gave the surprising result that the 5HT(1A) receptor was capable of forming hetero-oligomers with all GPCRs tested including the 5HT(1B), 5HT(1D), EDG(1), EDG(3), GPR(26), and GABA(B2) receptors. The testing of other GPCR combinations showed similar results with hetero-oligomer formation occurring for the 5HT(1D) with the 5HT(1B) and EDG(1) receptor. Control studies showed that these complexes were present in co-transfected cells before the time of lysis and that the hetero-oligomers were comprised of GPCRs at discrete stoichiometries. These findings suggest that GPCRs have a natural tendency to form oligomers when co-transfected into cells. Future studies should therefore investigate the presence and physiological role of GPCR hetero-oligomers in cells in which they are endogenously expressed.
Cord UIs (2015)

Cord UIs are sensorial augmented cords that allow for simple metaphor-rich interactions to interface with their connected devices. Cords offer a large underexplored space for interactions as well as unique properties and a diverse set of metaphors that make them potentially interesting tangible interfaces. We use cords as input devices and explore different interactions like tying knots, stretching, pinching and kinking to control the flow of data and/or power. We also look at ways to use objects in combination with augmented cords to manipulate data or properties of a device. For instance, placing a clamp on a cable can obstruct the audio signal to the headphones. Using special materials such as piezo copolymer cables and stretchable cords we built five working prototypes to showcase the interactions described in this paper.
Fixed point theorems of GPS carrier phase ambiguity resolution and their application to massive network processing: Ambizap (2008)

Precise point positioning (PPP) has become popular for Global Positioning System (GPS) geodetic network analysis because for n stations, PPP has O ( n ) processing time, yet solutions closely approximate those of O ( n 3 ) full network analysis. Subsequent carrier phase ambiguity resolution (AR) further improves PPP precision and accuracy; however, full‐network bootstrapping AR algorithms are O ( n 4 ), limiting single network solutions to n &lt; 100. In this contribution, fixed point theorems of AR are derived and then used to develop “Ambizap,” an O ( n ) algorithm designed to give results that closely approximate full network AR. Ambizap has been tested to n ≈ 2800 and proves to be O ( n ) in this range, adding only ∼50% to PPP processing time. Tests show that a 98‐station network is resolved on a 3‐GHz CPU in 7 min, versus 22 h using O ( n 4 ) AR methods. Ambizap features a novel network adjustment filter, producing solutions that precisely match O ( n 4 ) full network analysis. The resulting coordinates agree to ≪1 mm with current AR methods, much smaller than the ∼3‐mm RMS precision of PPP alone. A 2000‐station global network can be ambiguity resolved in ∼2.5 h. Together with PPP, Ambizap enables rapid, multiple reanalysis of large networks (e.g., ∼1000‐station EarthScope Plate Boundary Observatory) and facilitates the addition of extra stations to an existing network solution without need to reprocess all data. To meet future needs, PPP plus Ambizap is designed to handle ∼10,000 stations per day on a 3‐GHz dual‐CPU desktop PC.