gebhart/patrepeval huggingface dataset:
Generation of potent mouse monoclonal antibodies to self-proteins using T-cell epitope “tags” (2014)

Immunization of mice or rats with a "non-self" protein is a commonly used method to obtain monoclonal antibodies, and relies on the immune system's ability to recognize the immunogen as foreign. Immunization of an antigen with 100% identity to the endogenous protein, however, will not elicit a robust immune response. To develop antibodies to mouse proteins, we focused on the potential for breaking such immune tolerance by genetically fusing two independent T-cell epitope-containing sequences (from tetanus toxin (TT) and diphtheria toxin fragment A (DTA)) to a mouse protein, mouse ST2 (mST2). Wild-type CD1 mice were immunized with three mST2 tagged proteins (Fc, TT and DTA) and the specific serum response was determined. Only in mice immunized with the T-cell epitope-containing antigens were specific mST2 serum responses detected; hybridomas generated from these mice secreted highly sequence-diverse IgGs that were capable of binding mST2 and inhibiting the interaction of mST2 with its ligand, mouse interleukin (IL)-33 (mIL-33). Of the hundreds of antibodies profiled, we identified five potent antibodies that were able to inhibit IL-33 induced IL-6 release in a mast cell assay; notably one such antibody was sufficiently potent to suppress IL-5 release and eosinophilia infiltration in an Alternaria alternata challenge mouse model of asthma. This study demonstrated, for the first time, that T-cell epitope-containing tags have the ability to break tolerance in wild-type mice to 100% conserved proteins, and it provides a compelling argument for the broader use of this approach to generate antibodies against any mouse protein or conserved ortholog.
Multiple Sclerosis—A Tuning Fork Still Required (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
The Dynamical Settling of Warped Disks and Angular Momentum Transport in Galaxies (1994)

We present results of three-dimensional, hydrodynamic models of gaseous disks settling in a nonspherical potential. As the gas settles, differential precession creates a warped disk similar to the warps seen in spiral galaxies. A logarithmic potential, indicative of a massive halo, seems to induce warps more extreme than those produced by a l/r potential with a quadrupole distortion.
Formalizing Visualization Design Knowledge as Constraints: Actionable and Extensible Models in Draco (2018)

There exists a gap between visualization design guidelines and their application in visualization tools. While empirical studies can provide design guidance, we lack a formal framework for representing design knowledge, integrating results across studies, and applying this knowledge in automated design tools that promote effective encodings and facilitate visual exploration. We propose modeling visualization design knowledge as a collection of constraints, in conjunction with a method to learn weights for soft constraints from experimental data. Using constraints, we can take theoretical design knowledge and express it in a concrete, extensible, and testable form: the resulting models can recommend visualization designs and can easily be augmented with additional constraints or updated weights. We implement our approach in Draco, a constraint-based system based on Answer Set Programming (ASP). We demonstrate how to construct increasingly sophisticated automated visualization design systems, including systems based on weights learned directly from the results of graphical perception experiments.
Universal Adversarial Perturbations Against Semantic Image Segmentation (2017)

While deep learning is remarkably successful on perceptual tasks, it was also shown to be vulnerable to adversarial perturbations of the input. These perturbations denote noise added to the input that was generated specifically to fool the system while being quasi-imperceptible for humans. More severely, there even exist universal perturbations that are input-agnostic but fool the network on the majority of inputs. While recent work has focused on image classification, this work proposes attacks against semantic image segmentation: we present an approach for generating (universal) adversarial perturbations that make the network yield a desired target segmentation as output. We show empirically that there exist barely perceptible universal noise patterns which result in nearly the same predicted segmentation for arbitrary inputs. Furthermore, we also show the existence of universal noise which removes a target class (e.g., all pedestrians) from the segmentation while leaving the segmentation mostly unchanged otherwise.
Glucagon-like peptide-1(7–36)amide and glucose-dependent insulinotropic polypeptide secretion in response to nutrient ingestion in man: acute post-prandial and 24-h secretion patterns (1993)

The acute effects of different macronutrients on the secretion of glucagon-like peptide-1(7-36)amide (GLP-1(7-36)amide) and glucose-dependent insulinotropic polypeptide (GIP) were compared in healthy human subjects. Circulating levels of the two hormones were measured over a 24-h period during which subjects consumed a mixed diet. In the first study, eight subjects consumed three equicaloric (375 kcal) test meals of carbohydrate, fat and protein. Small increases in plasma GLP-1(7-36) amide were found after all meals. Levels reached a maximum 30 min after the carbohydrate and 150 min after the fat load. Ingestion of both carbohydrate and fat induced substantial rises in GIP secretion, but the protein meal had no effect. In a second study, eight subjects consumed 75 g glucose or the equivalent portion of complex carbohydrate as boiled brown rice or barley. Plasma GIP, insulin and glucose levels increased after all three meals, the largest increase being observed following glucose and the smallest following the barley meal. Plasma GLP-1(7-36)amide levels rose only following the glucose meal. In the 24-h study, plasma GLP-1(7-36)amide and GIP concentrations were increased following every meal and remained elevated throughout the day, only falling to fasting levels at night. The increases in circulating GLP-1(7-36)amide and GIP levels following carbohydrate or a mixed meal are consistent with their role as incretins. The more sustained rises observed in the daytime during the 24-h study are consistent with an anabolic role in lipid metabolism.
ANTITUBERCULOUS IMMUNITY INDUCED IN MICE BY VACCINATION WITH LIVING CULTURES OF ATTENUATED TUBERCLE BACILLI (1953)

The immunity induced in mice by vaccination with living attenuated cultures of tubercle bacilli was measured by two criteria. (a) Increase in survival time of the vaccinated animals after infection with a dose of virulent bacilli sufficient to kill all the unvaccinated controls within 10 to 20 days. (b) Difference in the number of living bacilli recovered from the spleen and lungs of vaccinated and normal animals infected with a small dose of virulent bacilli. The level of immunity induced was found to depend upon the extent of multiplication in vivo of the bacilli used for vaccination. This in turn was conditioned by the degree of attenuation characteristic of the bacterial strain used in the preparation of the vaccine, the amount of vaccine injected, the route of vaccination, and the time interval between vaccination and challenge infection. It was possible to prevent or retard the development of immunity by treating the mice in course of immunization with a drug, isoniazid, capable of interrupting the multiplication in vivo of the bacilli used as vaccine. Although immunity regularly developed and lasted for many weeks when the proper conditions of vaccination were used, the immune response was never sufficient to protect the animals against ultimate death from infection with virulent tubercle bacilli. The prolongation of life in the vaccinated mice was not consequent on a direct bactericidal effect but rather on a retarded or interrupted multiplication of the virulent bacilli in vivo. The quantitative bacteriological techniques used in the present study would appear to be of value for the analysis of certain problems of immunity, and for the appraisal of vaccines and techniques of vaccination.
Selective and divided attention during visual discriminations of shape, color, and speed: functional anatomy by positron emission tomography (1991)

Positron emission tomography (PET) was used to identify the neural systems involved in discriminating the shape, color, and speed of a visual stimulus under conditions of selective and divided attention. Psychophysical evidence indicated that the sensitivity for discriminating subtle stimulus changes in a same-different matching task was higher when subjects selectively attended to one attribute than when they divided attention among the attributes. PET measurements of brain activity indicated that modulations of extrastriate visual activity were primarily produced by task conditions of selective attention. Attention to speed activated a region in the left inferior parietal lobule. Attention to color activated a region in the collateral sulcus and dorsolateral occipital cortex, while attention to shape activated collateral sulcus (similarly to color), fusiform and parahippocampal gyri, and temporal cortex along the superior temporal sulcus. Outside the visual system, selective and divided attention activated nonoverlapping sets of brain regions. Selective conditions activated globus pallidus, caudate nucleus, lateral orbitofrontal cortex, posterior thalamus/colliculus, and insular-premotor regions, while the divided condition activated the anterior cingulate and dorsolateral prefrontal cortex. The results in the visual system demonstrate that selective attention to different features modulates activity in distinct regions of extrastriate cortex that appear to be specialized for processing the selected feature. The disjoint pattern of activations in extravisual brain regions during selective- and divided-attention conditions also suggests that preceptual judgements involve different neural systems, depending on attentional strategies.
A Mechanism for TCR Sharing between T Cell Subsets and Individuals Revealed by Pyrosequencing (2011)

The human naive T cell repertoire is the repository of a vast array of TCRs. However, the factors that shape their hierarchical distribution and relationship with the memory repertoire remain poorly understood. In this study, we used polychromatic flow cytometry to isolate highly pure memory and naive CD8(+) T cells, stringently defined with multiple phenotypic markers, and used deep sequencing to characterize corresponding portions of their respective TCR repertoires from four individuals. The extent of interindividual TCR sharing and the overlap between the memory and naive compartments within individuals were determined by TCR clonotype frequencies, such that higher-frequency clonotypes were more commonly shared between compartments and individuals. TCR clonotype frequencies were, in turn, predicted by the efficiency of their production during V(D)J recombination. Thus, convergent recombination shapes the TCR repertoire of the memory and naive T cell pools, as well as their interrelationship within and between individuals.
Goodbye Warts, Hello Vitiligo: Candida Antigen‐Induced Depigmentation (2012)

Depigmentation after the use of topical immune modulators is a rare but reported event. Herein we present what is to our knowledge the first case of vitiligo at a site of Candida antigen injection.
Characterization of hydroxypropyl-beta-cyclodextrins used in the treatment of Niemann-Pick Disease type C1 (2017)

2-Hydroxypropyl-beta-cyclodextrin (HPβCD) has gained recent attention as a potential therapeutic intervention in the treatment of the rare autosomal-recessive, neurodegenerative lysosomal storage disorder Niemann-Pick Disease Type C1 (NPC1). Notably, HPβCD formulations are not comprised of a single molecular species, but instead are complex mixtures of species with differing degrees of hydroxypropylation of the cyclodextrin ring. The degree of substitution is a critical aspect of the complex mixture as it influences binding to other molecules and thus could potentially modulate biological effects. VTS-270 (Kleptose HPB) and Trappsol® Cyclo™ are HPβCD products under investigation as novel treatments for NPC1. The purpose of the present work is to compare these two different products; analyses were based on ion distribution and abundance profiles using mass spectrometry methodology as a means for assessing key molecular distinctions between products. The method incorporated electrospray ionization and analysis with a linear low-field ion mobility quadrupole time-of-flight instrument. We observed that the number of hydroxypropyl groups (the degrees of substitution) are substantially different between the two products and greater in Trappsol Cyclo than in VTS-270. The principal ions of both samples are ammonium adducts. Isotope clusters for each of the major ions show doubly charged homodimers of the ammonium adducts. In addition, both products show doubly charged homodimers from adduction of both a proton and ammonium. Doubly charged heterodimers are also present, but are more intense in Trappsol Cyclo than in VTS-270. Based on the analytical differences observed between VTS-270 and Trappsol Cyclo with respect to the degree of substitution, the composition and fingerprint of the complex mixture, and the impurity profiles, these products cannot be considered to be the same; the potential biological and clinical implications of these differences are not presently known.
Design-to-time real-time scheduling (1996)

Design-to-time is an approach to problem-solving in resource-constrained domains where: multiple solution methods are available for tasks, those solution methods make tradeoffs in solution quality versus time, and satisficing solutions are acceptable. Design-to-time involves designing a solution to a problem that uses all available resources to maximize the solution quality within the available time. This paper defines the design-to-time approach in detail, contrasting it to the anytime algorithm approach, and presents a heuristic algorithm for design-to-time real-time scheduling. Our blackboard architecture that implements the design-to-time approach is discussed and an example problem and solution from the Distributed Vehicle Monitoring Testbed (DVMT) is described in detail. Experimental results, generated using a simulation, show the effects of various parameters on scheduler performance. Finally we discuss future research goals and plans.
Training and evaluation of a spoken language understanding system (1990)

This paper describes our results on a spoken language application for finding directions. The spoken language system consists of the MIT SUMMIT speech recognition system ([20]) loosely coupled to the UNISYS PUNDIT language understanding system ([9]) with SUMMIT providing the top N candidates (based on acoustic score) to the PUNDIT system. The direction finding capability is provided by an expert system which is also part of the MIT VOYAGER system [18]).
Purified plasma factor XIIa aggregates human neutrophils and causes degranulation (1986)

Plasma kallikrein has been shown to aggregate human neutrophils and release human neutrophil elastase. However, neutrophils resuspended in factor XII-deficient plasma released only 30% of the elastase compared with normal plasma. Isolated human neutrophils were aggregated in a concentration-dependent fashion by 0.06 to 0.6 U/mL factor XIIa (0.022 to 0.22 mumol/L). Factor XIIa (0.1 to 1.0 U/mL) also induced neutrophil degranulation as evidenced by a concentration-dependent release of the specific granule protein, lactoferrin, and azurophilic granule protease, elastase. The release of neutrophil elastase was biphasic, reaching 40% of maximum at 15 seconds with maximal release by 90 minutes. The active site of factor XIIa was required, since the synthetic inhibitor, D-Pro-Phe-Arg-CH2Cl, which reacts with an essential histidine, and the natural plasma inhibitor, Cl-inhibitor, which interacts with the critical serine, both inhibit by more than 90% the release of elastase. The heavy chain is also required, since factor XII fragments failed to aggregate neutrophils or stimulate degranulation. Factor XIIa (0.6 U/mL) can completely correct the defect in elastase release evident in factor XII-deficient plasma. These studies demonstrate that factor XIIa, at concentrations potentially obtainable in plasma in disease states, can activate neutrophils, and thus may participate in the inflammatory response.
Synthetic well logs generation via Recurrent Neural Networks (2018)

To supplement missing logging information without increasing economic cost, a machine learning method to generate synthetic well logs from the existing log data was presented, and the experimental verification and application effect analysis were carried out. Since the traditional Fully Connected Neural Network (FCNN) is incapable of preserving spatial dependency, the Long Short-Term Memory (LSTM) network, which is a kind of Recurrent Neural Network (RNN), was utilized to establish a method for log reconstruction. By this method, synthetic logs can be generated from series of input log data with consideration of variation trend and context information with depth. Besides, a cascaded LSTM was proposed by combining the standard LSTM with a cascade system. Testing through real well log data shows that: the results from the LSTM are of higher accuracy than the traditional FCNN; the cascaded LSTM is more suitable for the problem with multiple series data; the machine learning method proposed provides an accurate and cost effective way for synthetic well log generation.
Post-remission therapy for acute myeloid leukemia (2014)

Induction followed by post-remission therapy including intensive chemotherapy with high-dose cytarabine, autologous and allogeneic hematopoietic stem cell transplantation is recognized as the main road towards cure in acute myeloid leukemia. In recent years, also a renaissance of maintenance therapy after completion of intensive consolidation has been observed with the introduction of kinase inhibitors and demethylating agents in clinical trials. Greater insight into the genetic background of the disease fostered the extension of disease classification and pretreatment risk-categorization by gene mutations. In addition, the pre-treatment risk-defining parameters have been supplemented by markers evaluated at distinct time points during treatment and follow up. In this context, minimal residual disease assessment is increasingly used to dynamically fine tune treatment recommendations. Currently, the gold standard to counterbalance a higher risk of relapse by treatment strategies based on hematopoietic stem cell transplantation with grafts from matched related or unrelated donors is still valuable, whereas autologous hematopoietic stem cell transplantation showed promising results especially in patients categorized as low-risk. Nonetheless, more targeted approaches including kinase inhibitors and demethylating agents in combination with or sequentially before or after intensive chemotherapy are currently in clinical evaluation and may lead to more genotype- instead of purely risk-adapted treatment strategies.
The Apolipoprotein ε4 Allele Determines Prognosis and the Effect on Prognosis of Simvastatin in Survivors of Myocardial Infarction (2000)

Myocardial infarction survivors with the epsilon4 allele have a nearly 2-fold increased risk of dying compared with other patients, and the excess mortality can be abolished by treatment with simvastatin.
Evidence for the involvement of a plasma kallikrein‐kinin system in the immediate hypotension produced by endotoxin in anaesthetized rats (1989)

1. In vitro incubation of normal rat plasma with endotoxin from E. coli (3-10 mg ml-1) in the incubation mixture) caused a dose-dependent increase in levels of free kinin and plasma kallikrein in the presence of o-phenanthroline, together with a mirror-image, dose-dependent decrease in the residual levels of the precursors, plasma prekallikrein and high-molecular-weight kininogen. Low-molecular-weight kininogen levels were not modified. 2. Intravenous injection of endotoxin (3-30 mg kg-1) into the femoral vein of anaesthetized rats resulted in dose-dependent hypotension. In blood collected up to 15 min after injection, the levels of prekallikrein and high-molecular-weight kininogen in plasma were decreased while levels of the active forms, plasma kallikrein and free kinin, showed a transient increase in the blood 1 min after administration of endotoxin. 3. A degradation product of bradykinin, des-Phe8-Arg9-bradykinin, as measured by a newly developed enzyme immunoassay, was detectable up to 5 min after administration of endotoxin. 4. Intravenous infusion of soybean trypsin inhibitor inhibited both the formation of bradykinin and des-Phe8-Arg9-bradykinin and the initial hypotension. 5. It can be concluded from our results that plasma prekallikrein is activated in the blood immediately after administration of endotoxin to rats and that bradykinin is a major cause of the immediate hypotension.
Transcranial Electrical Stimulation Accelerates Human Sleep Homeostasis (2013)

The sleeping brain exhibits characteristic slow-wave activity which decays over the course of the night. This decay is thought to result from homeostatic synaptic downscaling. Transcranial electrical stimulation can entrain slow-wave oscillations (SWO) in the human electro-encephalogram (EEG). A computational model of the underlying mechanism predicts that firing rates are predominantly increased during stimulation. Assuming that synaptic homeostasis is driven by average firing rates, we expected an acceleration of synaptic downscaling during stimulation, which is compensated by a reduced drive after stimulation. We show that 25 minutes of transcranial electrical stimulation, as predicted, reduced the decay of SWO in the remainder of the night. Anatomically accurate simulations of the field intensities on human cortex precisely matched the effect size in different EEG electrodes. Together these results suggest a mechanistic link between electrical stimulation and accelerated synaptic homeostasis in human sleep.