gebhart/patrepeval huggingface dataset:
Recombinant allergen molecules: tools to study effector cell activation (2001)

The IgE antibody-mediated activation of allergic effector cells is the key pathomechanism underlying the immediate symptoms of Type I allergy, a genetically determined hypersensitivity disease affecting 25% of the population. In recent years important environmental allergens and their epitopes have become available as structurally defined recombinant molecules. In addition, corresponding human monoclonal IgE and IgG antibodies have been isolated. This review summarizes data obtained regarding the three-dimensional structure of allergens, their IgE epitopes and the recognition of allergens by IgE and IgG antibodies. In particular, we discuss results of recent in vitro and in vivo studies with defined allergen molecules, their epitopes and the corresponding antibodies which support the hypothesis that the density and geometrical arrangement of IgE epitopes on a particular allergen molecule may profoundly affect effector cell activation. If the structural requirements for effector cell activation can be delineated, it may be envisaged that, based on this knowledge, allergens can be converted into hypoallergenic immunogens by reorientation of IgE epitopes. Such allergen derivatives may be used for allergen-specific immunotherapy with reduced risk of inducing anaphylactic side effects.
Review: Misoprostol or COX-2–specific or selective NSAIDs reduce gastrointestinal complications and symptomatic ulcers (2005)

Source Citation Hooper L, Brown TJ, Elliott R, et al. The effectiveness of five strategies for the prevention of gastrointestinal toxicity induced by non-steroidal anti-inflammatory drugs: systematic review. BMJ. 2004;329:948. 15475342
Broadband antireflection with curved surface nano-pyramids for image sensing devices (2016)

The reflection loss in imaging devices is one of the major drawbacks, which degrades efficiency resulting in lower responsivity. Since the reflected light is no longer available for conversion into electrons, it is very important to reduce the reflection from the top surface of the device as much as possible. Quarter wavelength and two index antireflection (AR) coatings have been developed to reduce reflection; however, these AR coatings are wavelength dependent and have not performed effectively in a broadband range. Attempts to make AR coating for broadband wavelengths by stacking multiple index AR layers result in thicker and expensive solutions, which still do not provide proper antireflection at all desired wavelengths. Moreover, the usage of AR coatings escalates material and fabrication costs of the device. We propose a novel nanostructure, which matches the refractive index of the device to that of free space to reduce reflection from the top surface, eliminating the use of AR coatings and hence reducing the device cost. It is shown via simulation that the proposed nanostructure effectively eliminates the reflection loss over the broadband spectrum of desired wavelengths e.g. Visible, Mid-wave IR (MWIR), Short-wave IR (SWIR) spectrums, opening various application opportunities.
Molecular Recognition of Diverse Ligands by T-Cell Receptors (2009)

T-cell receptors (TCRs) are structurally related to antibodies, and also interact with a diverse set of ligands. TCRs recognize foreign peptide antigens displayed by major histocompatibility complex (MHC) molecules and foreign lipid-based antigens presented by CD1. These interactions initiate an immune response through T-cell activation. These critical surveillance and response initiation functions of the adaptive immune system are not perfect, though, as TCR interactions with self antigens can lead to autoimmune disease. Mutated peptides can also be recognized specifically by TCRs, and may be important in tumor immunity. TCRs are also bound specifically by a family of bacterial toxins called superantigens, which over-stimulate the immune system to cause numerous human diseases.
Chloride channel accessory 1 gene deficiency causes selective loss of mucus production in a new pig model (2022)

Morbidity and mortality of respiratory diseases are linked to airway obstruction by mucus but there are still no specific, safe, and effective drugs to correct this phenotype. The need for better treatment requires a new understanding of the basis for mucus production. In that regard, studies of human airway epithelial cells in primary culture show that a mucin granule constituent known as chloride channel accessory 1 (CLCA1) is required for inducible expression of the inflammatory mucin MUC5AC in response to potent type 2 cytokines. However, it remained uncertain whether CLCLA1 is necessary for mucus production in vivo. Conventional approaches to functional biology using targeted gene knockout were difficult due to the functional redundancy of additional <i>Clca</i> genes in mice not found in humans. We reasoned that CLCA1 function might be better addressed in pigs that maintain the same four-member <i>CLCA</i> gene locus and the corresponding mucosal and submucosal populations of mucous cells found in humans. Here we develop to our knowledge the first <i>CLCA1</i>-gene-deficient (<i>CLCA1<sup>-/-</sup></i>) pig and show that these animals exhibit loss of MUC5AC<sup>+</sup> mucous cells throughout the airway mucosa of the lung without affecting comparable cells in the tracheal mucosa or MUC5B<sup>+</sup> mucous cells in submucosal glands. Similarly, <i>CLCA1<sup>-/-</sup></i> pigs exhibit loss of MUC5AC<sup>+</sup> mucous cells in the intestinal mucosa without affecting MUC2<sup>+</sup> mucous cells. These data establish CLCA1 function for controlling MUC5AC expression as a marker of mucus production and provide a new animal model to study mucus production at respiratory and intestinal sites.
Genetics as Explanation: Limits to the Human Genome Project (2009)

Abstract Living organisms are composed of cells and all living cells contain a genome, the organism's stock of deoxyribonucleic acid (DNA). The role of the genome has been likened to a program that encodes the organism's development and its subsequent response to the environment. This computer metaphor teaches that the organism – the hardware – is controlled by the software – the genome. Thus, the organism and its fate can be explained by genetics, the plans written into the sequence of genomic DNA; the Genome Project was devised to decipher this program. However, it is now clear that the genome does not directly program the organism; the computer program metaphor has misled us. The genome is only one class of vital information that serves the organism. Metaphorically, the genome can be likened to a vocabulary of words that can be deployed to make meaningful sentences, or to a toolbox for accomplishing specific tasks. Key concepts: The genome does not function as a master plan or computer program for controlling the organism; the genome is the organism's servant, not its master. The genome is a reservoir of DNA sequence information and a vehicle for transmitting this information; the meaning of DNA emerges from the cellular processing of this raw information into proteins and other functional molecules. DNA is only one class of vital information that serves the organism; the organism epigenetically uses, manipulates, regulates and, in the case of the immune system, creates genes. The effects of a gene vary with the organism's environment; the interactions between genes and environment are not linear and, in most cases, not additive. Therefore, one cannot compute with certainty the relative contributions of genes and environment to an organism's observed features – its phenotype. Metaphorically, we can think of the genome as akin to a list of words, a vocabulary, which can be used to build and express a meaningful language; like a vocabulary, a genome by itself has no functional meaning. The genome is thus akin to a toolbox of DNA sequences that provide molecular tools as requested by the internal state of the organism and the state of the environment. One's genes cannot explain one's being: an organism is the expression of a dynamic and ongoing interaction between the state of its environment and its internal state, which includes its past history and its toolbox of DNA sequences.
The role of tau protein in HIV-associated neurocognitive disorders (2014)

Given the increased life expectancy of human immunodeficiency virus (HIV) infected individuals treated with combination antiretroviral therapy (cART) and the ongoing inflammation observed in the brains of these patients, it is likely that premature neurodegeneration as measured by phospho-tau (p-tau) or increased total tau (t-tau) protein may become an increasing problem. This review examines the seven human studies that have occurred over the past 14 years measuring p-tau and/or t-tau in cerebrospinal fluid (CSF) or via post-mortem brain immunohistochemistry. Although not all studies are in agreement as to the changes in p-and t-tau in HIV infected patients, HIV persists in the brain despite cART. Thus is it is suggested that those maintained on long-term cART may develop tau pathology beyond the extent seen in the studies reviewed herein and overtime may then reach the threshold for clinical manifestation.
Systematic study of surface morphology, photoluminescence efficiency, and spin-detection sensitivity in (110)-oriented GaAs/AlGaAs quantum wells (2016)

Abstract We prepared (110)-oriented GaAs/AlGaAs multiple-quantum-well (MQW) samples by molecular beam epitaxy (MBE) under different growth conditions, and conducted systematic measurements of surface morphology, photoluminescence (PL), and spin-detection sensitivity at room temperature. Excellent surface flatness and high PL intensity were observed for the samples grown at temperatures ≥450 °C and As 4 /Ga flux ratios ≥40. It was found that the PL intensity of (110) MQWs was higher than that of the conventional (100) MQWs grown using the same MBE system. At the same time, we confirmed that the spin-detection sensitivity of (110) MQWs we obtained was an order of magnitude higher than that of the (100) MQWs. These results suggest that the newly developed (110) MQWs indeed have greater advantages than the conventional (100) MQWs for use in emerging spin-optical devices such as spin-controlled lasers.
Efficacy of APX2039 in a Rabbit Model of Cryptococcal Meningitis (2022)

Cryptococcal Meningitis (CM) is uniformly fatal if not treated, and treatment options are limited. We previously reported on the activity of APX2096, the prodrug of the novel Gwt1 inhibitor APX2039, in a mouse model of CM. Here, we investigated the efficacy of APX2039 in mouse and rabbit models of CM. In the mouse model, the controls had a mean lung fungal burden of 5.95 log<sub>10</sub> CFU/g, whereas those in the fluconazole-, amphotericin B-, and APX2039-treated mice were 3.56, 4.59, and 1.50 log<sub>10</sub> CFU/g, respectively. In the brain, the control mean fungal burden was 7.97 log<sub>10</sub> CFU/g, while the burdens were 4.64, 7.16, and 1.44 log<sub>10</sub> CFU/g for treatment with fluconazole, amphotericin B, and APX2039, respectively. In the rabbit model of CM, the oral administration of APX2039 at 50 mg/kg of body weight twice a day (BID) resulted in a rapid decrease in the cerebrospinal fluid (CSF) fungal burden, and the burden was below the limit of detection by day 10 postinfection. The effective fungicidal activity (EFA) was -0.66 log<sub>10</sub> CFU/mL/day, decreasing from an average of 4.75 log<sub>10</sub> CFU/mL to 0 CFU/mL, over 8 days of therapy, comparing favorably with good clinical outcomes in humans associated with reductions of the CSF fungal burden of -0.4 log<sub>10</sub> CFU/mL/day, and, remarkably, 2-fold the EFA of amphotericin B deoxycholate in this model (-0.33 log<sub>10</sub> CFU/mL/day). A total drug exposure of the area under the concentration-time curve from 0 to 24 h (AUC<sub>0-24</sub>) of 25 to 50 mg · h/L of APX2039 resulted in near-maximal antifungal activity. These data support the further preclinical and clinical evaluation of APX2039 as a new oral fungicidal monotherapy for the treatment of CM. <b>IMPORTANCE</b> Cryptococcal meningitis (CM) is a fungal disease with significant global morbidity and mortality. The gepix Gwt1 inhibitors are a new class of antifungal drugs. Here, we demonstrated the efficacy of APX2039, the second member of the gepix class, in rabbit and mouse models of cryptococcal meningitis. We also analyzed the drug levels in the blood and cerebrospinal fluid in the highly predictive rabbit model and built a mathematical model to describe the behavior of the drug with respect to the elimination of the fungal pathogen. We demonstrated that the oral administration of APX2039 resulted in a rapid decrease in the CSF fungal burden, with an effective fungicidal activity of -0.66 log<sub>10</sub> CFU/mL/day, comparing favorably with good clinical outcomes in humans associated with reductions of -0.4 log<sub>10</sub> CFU/mL/day. The drug APX2039 had good penetration of the central nervous system and is an excellent candidate for future clinical testing in humans for the treatment of CM.
Inhibition of experimental visceral pain in rodents by cebranopadol (2018)

The aim of this study was to investigate the efficacy of cebranopadol in two rodent models of visceral pain. Cebranopadol is a first-in-class analgesic with agonist activity at the nociceptin/orphanin FQ opioid peptide receptor and classical µ-, δ- and κ-opioid peptide receptors. Colitis was induced in Naval Medical Research Institute mice by intra-rectal infusion of mustard oil. The effects of intravenous cebranopadol pretreatment on spontaneous pain behaviours and referred allodynia and hyperalgesia were assessed. Pancreatitis was induced in Sprague-Dawley rats by intravenous administration of dibutyltin dichloride. After 6 days, the effects of intravenous cebranopadol on withdrawal reactions to mechanical abdominal stimulation with von Frey filaments were assessed. In mice with experimental colitis, cebranopadol dose-dependently inhibited spontaneous pain behaviours and allodynic and hyperalgesic withdrawal reactions, with half-maximal effective dose values of 4.6 µg/kg [95% confidence interval (CI): 2.9-7.9] for inhibition of spontaneous pain behaviours, 2.2 µg/kg (95% CI: 1.3-3.4) for inhibition of referred allodynia and 2.4 µg/kg (95% CI: 1.4-3.6) for inhibition of referred hyperalgesia in mice with colitis. In rats with experimental pancreatitis, cebranopadol dose-dependently inhibited abdominal tactile allodynia (half-maximal effective dose, 0.13 µg/kg; 95% CI: 0.03-0.49). Behavioural manifestations of visceral pain were almost completely abolished at the highest doses tested in mice (17.2 µg/kg, intravenous) and rats (2.4 µg/kg, intravenous). We conclude that cebranopadol is a potent and effective antiallodynic and antihyperalgesic agent in rodent models of visceral pain.
Chemoenzymatic Synthesis of the Polyketide Macrolactone 10-Deoxymethynolide (2005)

The polyketide synthase-derived pikromycin thioesterase (Pik TE) is unique in its ability to catalyze the cyclization of 12- and 14-membered macrolactones. In this investigation, the total synthesis of the natural hexaketide chain elongation intermediate as its N-acetyl cysteamine (NAC) thioester has been achieved, and its reaction with Pik TE demonstrated the ability of Pik TE to catalyze its macrolactonization to the natural product 10-deoxymethynolide. A steady-state kinetic analysis of the hexaketide chain intermediate with Pik TE was done. A preliminary substrate specificity study with unnatural hexaketide analogues was accomplished, demonstrating the importance of total synthesis in obtaining access to advanced polyketide intermediates. The results show the sensitivity of Pik TE to minor substrate modifications, and illustrate the potential use of thioesterases as versatile macrolactonization catalysts.
Novel approaches to thrombolysis based on modulation of endogenous fibrinolysis (1998)

Stefansson, Steingrimura; Lawrence, Daniel A.a; Herren, Thomasb; Plow, Edward F.c Author Information
Performance Assessment of Molecular Sieves for Sulfur Recovery Unit Tail Gas Treating (2023)

Due to stricter worldwide environmental mandates on SO2 emission from oil and gas industrial facilities, the modified Claus process, which is the primary tool for reducing emission of SO2 into the atmosphere in these facilities, has undergone a lot of innovative changes during the past decades. An example of such innovation is the addition of what is called tail gas treating (TGT) technologies. Currently, advanced TGT technologies ensure that gas plants and refineries emit less than 0.01% (v/v) of the sulfur species that enter into the sulfur recovery units; they commonly use absorption-based processes to separate sulfur species from the tail gas. Because of this requirement, TGT technologies are expensive. This paper reports the data that were obtained from bench-scale tests that were carried out to assess the feasibility of using commercially available adsorbents for the process that is described in the patent, Two-Stage Adsorption Process for Claus Tail Gas Treatment, US Patent No.10662061. In one of the embodiments of this process, the tail gas is treated in two steps. It is first dehydrated by 3A molecular sieves and then by 5A molecular sieves to remove H2S. The separation in the second step will ensure the presence of a rich H2S-laden stream that is ready for routing to the thermal reactor of the modified Claus process. The data collected in this study indicate the following: (1) Commercial molecular sieves can be used for cost-effective tail gas treatment of natural gas plants’ and refineries’ sulfur recovery units. (2) This cost-effectiveness of such use can be valid when molecular sieve material selection is as described in US Patent No.10662061, “Two-Stage Adsorption Process for Claus Tail Gas Treatment”. (3) Adsorption-based tail gas treatment is advantageous since it results in enabling the global oil and gas industry to virtually eliminate all SO2 emissions from its facilities.
The dry chain: Reducing postharvest losses and improving food safety in humid climates (2017)

Even as increasing populations put pressure on food supplies, about one-third of the total food produced for human consumption is wasted, with the majority of loss in developing countries occurring between harvest and the consumer. Controlling product dryness is the most critical factor for maintaining quality in stored non-perishable foods. The high relative humidity prevalent in humid climates elevates the moisture content of dried commodities stored in porous woven bags, enabling fungal and insect infestations. Mycotoxins (e.g., aflatoxin) produced by fungi in insufficiently dried food commodities affect 4.5 billion people worldwide. We introduce the term “dry chain” to describe initial dehydration of durable commodities to levels preventing fungal growth followed by storage in moisture-proof containers. This is analogous to the “cold chain” in which continuous refrigeration is used to preserve quality in the fresh produce industry. However, in the case of the dry chain, no further equipment or energy input is required to maintain product quality after initial drying as long as the integrity of the storage container is preserved. In some locations/seasons, only packaging is required to implement a “climate smart” dry chain, while in humid conditions, additional drying is required and desiccant-based drying methods have unique advantages. We propose both climate-based and drying-based approaches to implement the dry chain to minimize mycotoxin accumulation and insect infestations in dry products, reduce food loss, improve food quality, safety and security, and protect public health.
Data-Driven Integral Reinforcement Learning for Continuous-Time Non-Zero-Sum Games (2019)

This paper develops an integral value iteration (VI) method to efficiently find online the Nash equilibrium solution of two-player non-zero-sum (NZS) differential games for linear systems with partially unknown dynamics. To guarantee the closed-loop stability about the Nash equilibrium, the explicit upper bound for the discounted factor is given. To show the efficacy of the presented online model-free solution, the integral VI method is compared with the model-based off-line policy iteration method. Moreover, the theoretical analysis of the integral VI algorithm in terms of three aspects, i.e., positive definiteness properties of the updated cost functions, the stability of the closed-loop systems, and the conditions that guarantee the monotone convergence, is provided in detail. Finally, the simulation results demonstrate the efficacy of the presented algorithms.
Adsorption of phenol and 2,4-dichlorophenol on carbon-containing sorbent produced from sugar cane bagasse (2021)

An adsorbent prepared from carbonized sugar cane bagasse Cl shows high adsorption capacity to phenol and 2,4-dichlorophenol that is equal to 2.24 and 2.45 mmol g−1, respectively.
Classifying Induced Damage in Composite Plates Using One-Class Support Vector Machines (2010)

For many engineering and aerospace applications, detection and quantification of multiscale damage in fiber-reinforced composite structures is increasing in importance. Consequently, the development of an efficient and cost-effective diagnosis scheme that can accurately sense, characterize, and evaluate the existence of any form of damage will offer significant potential for improving the performance, reliability, and extending the operational life of these complex systems. We present an approach to characterize and classify different damage states in composite laminates by measuring the change in the signature of the resultant wave that propagates through the anisotropic media under forced excitation. The wave propagation is measured using surface-mounted piezoelectric transducers. Sensor signals collected from test specimens with various forms of induced damage are analyzed using a pattern-recognition algorithm known as the one-class support vector machines. The one-class support-vector-machine algorithm performs automatic anomaly detection and classification of damage signatures using various features from the sensor readings. The results obtained suggest that the one-class support-vector-machine algorithm, along with appropriate preprocessing techniques, can often achieve better accuracy than the popular k-nearest-neighbor method in detecting and classifying anomalies caused by structural defects, even when the perturbations caused in the sensor signals due to different damage states are minimal.