gebhart/patrepeval huggingface dataset:
Immunoglobulin specificity of TG19318: a novel synthetic ligand for antibody affinity purification (1998)

A synthetic ligand [TG19318], able to mimic protein A in the recognition of the immunoglobulin Fc portion, has been previously identified in our laboratory through the synthesis and screening of multimeric combinatorial peptide libraries. In this study we have fully characterized its applicability in affinity chromatography for the downstream processing of antibodies, examining the specificity and selectivity for polyclonal and monoclonal immunoglobulins derived from different sources. Ligand specificity was broader than protein A, since IgG deriving from human, cow, horse, pig, mouse, rat, rabbit, goat and sheep sera, IgY obtained from egg yolk, and IgM, IgA and IgE were efficiently purified on TG19318 affinity columns. Adsorbed antibodies were conveniently eluted by a buffer change to 0.1 M acetic acid or 0.1 M sodium bicarbonate pH 9, with full retention of immunological properties. Monoclonal antibodies deriving from cell culture supernatants or ascitic fluids were also conveniently purified on TG19318 affinity columns, even from very diluted samples. The affinity constant for the TG19318-IgG interaction was 0.3 microM, as determined by optical biosensor measurements. Under optimized conditions, antibody purity after affinity purification was close to 95%, as determined by densitometric scanning of SDS-PAGE gels of purified fractions, and maximal column capacity reached 25 mg Ig/ml support. In vivo toxicity studies in mice indicated a ligand oral toxicity greater than 2000 mg kg-1 while intravenous toxicity was close to 150 mg kg-1. Validation of antibody affinity purification processes for therapeutic use, a very complex, laborious and costly procedure, is going to be simplified by the use of TG19318, which could reduce considerably the presence of biological contaminants in the purified preparation, a very recurrent problem when using recombinant or extractive biomolecules as affinity ligands.
Drosophila HP1c Is Regulated by an Auto-Regulatory Feedback Loop through Its Binding Partner Woc (2009)

HP1 is a major component of chromatin and regulates gene expression through its binding to methylated histone H3. Most eukaryotes express at least three isoforms of HP1 with similar domain architecture. However, despite the common specificity for methylated histone H3, the three HP1 isoforms bind to different regions of the genome. Most of the studies so far focused on the HP1a isoform and its role in transcriptional regulation. As HP1a requires additional factors to bind methylated chromatin in vitro, we wondered whether another isoform might also require additional targeting factors. Indeed, we found that HP1c interacts with the DNA binding factors Woc and Row and requires Woc to become targeted to chromatin in vivo. Moreover, we show that the interaction between HP1c and Woc constitutes a transcriptional feedback loop that operates to balance the concentration of HP1c within the cell. This regulation may prevent HP1c from binding to methylated heterochromatin.
Nitric oxide regulates basal systemic and pulmonary vascular resistance in healthy humans. (1994)

This study demonstrates that basal release of endothelium-derived NO is directly involved in the determination of systemic vascular resistance and, therefore, blood pressure in healthy humans. In addition, NO regulates basal normoxic pulmonary vascular tone. The complex hemodynamic effects of NO are composite properties of its actions on systemic and pulmonary vascular resistance and cardiac function.
Evaluation of Dynamic Programming Based Methods and Multiple area Representation for Thermal Unit Commitments (1981)

This paper compares the performance of four unit commitment methods, three of which are based on the dynamic programming approach. The paper also presents the modeling of inter-area flow constraints by linear flow network, so that such multi-area representation recognizes any existing transmission limitations which are normally ignored in most unit commitment methods. To assure realistic results, data for two large systems (up to 96 units) were used: EPRI Scenario System C and a midwestern utility. Unit commitment results for these two systems are presented in the paper and they demonstrate the importance of multiple area representation of a system in unit commitment. Such representation affects the schedule costs and assures the determination of realizable schedules.
ICBS: The Improved Conflict-Based Search Algorithm for Multi-Agent Pathfinding (2021)

Conflict-Based Search (CBS) and its generalization, Meta-Agent CBS are amongst the strongest newly introduced algorithms for Multi-Agent Path Finding. This paper introduces ICBS, an improved version of CBS. ICBS incorporates three orthogonal improvements to CBS which are systematically described and studied. Experimental results show that each of these improvements reduces the runtime over basic CBS by up to 20x in many cases. When all three improvements are combined, an even larger improvement is achieved, producing state-ofthe art results for a number of domains.
Supplementary Table 1 from Expression of G Protein-Coupled Receptor 19 in Human Lung Cancer Cells Is Triggered by Entry into S-Phase and Supports G<sub>2</sub>–M Cell-Cycle Progression (2023)

&lt;p&gt;PDF file - 51K, Detailed cell line information for human NSCLC, SCLC, and normal lung cell lines and HEK-293 cells&lt;/p&gt;
Homology between surface protein antigen genes of Streptococcus sobrinus and Streptococcus mutans (1989)

The structural gene ( pag gene) for a 210 kDa protein antigen of Streptococcus sobrinus serotype g was cloned and compared with that ( pac gene) of a 190 kDa protein antigen of Streptococcus mutans serotype c . Immunodiffusion analysis revealed that the product of the pag gene immunologically cross‐reacted with that of the pac gene. Southern blot and nucleotide sequence analyses revealed that a significant homology existed between the middle regions of the two structural genes.
Stable and reproducible electronic conduction through DNA molecular junctions (2009)

This letter presents the observation of stable and reproducible electronic conduction through double stranded (ds) DNA molecules in a nominally dry state. Stable conduction was realized by immobilizing 15 base-pair guanine:cytosine rich dsDNA within gold nanogap junctions, stabilizing the dsDNA with a polycation, and characterizing in nitrogen. In air, the current levels decrease with successive voltage scans likely due to oxidation of the guanine bases under bias. In nitrogen, reproducible current-voltage traces are observed and the current levels at specific bias points are stable with time. The stability allows comprehensive electrical studies and could enable conductance-based DNA sensors.
Back-Pressure Effects of a RDE Area Rule (2022)

View Video Presentation: https://doi.org/10.2514/6.2022-0514.vid Rotating detonation engine instability is initiated by a sufficient closure of nozzle area relative to chamber and injection area. Sufficient closure results in increased back pressure and ultimately, detonation failure. The immediate cause of failure is loss of detonation height below a critical value estimated at one half of the detonation cell height. However, the causal chain is complex with evidence of a dynamic resonance. Precursors of unstable behavior are seen in progressive changes of the detonation wave velocity frequency spectrum. Thrust and Isp are shown to be proportional to the ratio of injection to nozzle throat area.
Pairwise heuristic sequence alignment algorithm based on deep\n reinforcement learning (2020)

Various methods have been developed to analyze the association between\norganisms and their genomic sequences. Among them, sequence alignment is the\nmost frequently used for comparative analysis of biological genomes. However,\nthe traditional sequence alignment method is considerably complicated in\nproportion to the sequences' length, and it is significantly challenging to\nalign long sequences such as a human genome. Currently, several multiple\nsequence alignment algorithms are available that can reduce the complexity and\nimprove the alignment performance of various genomes. However, there have been\nrelatively fewer attempts to improve the alignment performance of the pairwise\nalignment algorithm. After grasping these problems, we intend to propose a new\nsequence alignment method using deep reinforcement learning. This research\nshows the application method of the deep reinforcement learning to the sequence\nalignment system and the way how the deep reinforcement learning can improve\nthe conventional sequence alignment method.\n
Dust environment and dynamical history of a sample of short-period comets (2014)

Aims. This paper is a continuation of the first paper in this series, where we presented an extended study of the dust environment of a sample of short-period comets and their dynamical history. On this occasion, we focus on comets 81P/Wild 2 and 103P/Hartley 2, which are of special interest as targets of the spacecraft missions Stardust and EPOXI.
Transcriptomic Analysis of Yersinia enterocolitica Biovar 1B Infecting Murine Macrophages Reveals New Mechanisms of Extracellular and Intracellular Survival (2015)

Yersinia enterocolitica is typically considered an extracellular pathogen; however, during the course of an infection, a significant number of bacteria are stably maintained within host cell vacuoles. Little is known about this population and the role it plays during an infection. To address this question and to elucidate the spatially and temporally dynamic gene expression patterns of Y. enterocolitica biovar 1B through the course of an in vitro infection, transcriptome sequencing and differential gene expression analysis of bacteria infecting murine macrophage cells were performed under four distinct conditions. Bacteria were first grown in a nutrient-rich medium at 26 °C to establish a baseline of gene expression that is unrelated to infection. The transcriptomes of these bacteria were then compared to bacteria grown in a conditioned cell culture medium at 37 °C to identify genes that were differentially expressed in response to the increased temperature and medium but not in response to host cells. Infections were then performed, and the transcriptomes of bacteria found on the extracellular surface and intracellular compartments were analyzed individually. The upregulated genes revealed potential roles for a variety of systems in promoting intracellular virulence, including the Ysa type III secretion system, the Yts2 type II secretion system, and the Tad pilus. It was further determined that mutants of each of these systems had decreased virulence while infecting macrophages. Overall, these results reveal the complete set of genes expressed by Y. enterocolitica in response to infection and provide the groundwork for future virulence studies.
Incidence and survival trends for malignant pleural and peritoneal mesothelioma, Australia, 1982–2009 (2016)

Australia's malignant mesothelioma incidence rates appear to have reached maximum levels but with differences over time by age, gender and tumour location. Improvements over time in survival provide a glimpse of hope for this almost invariably fatal disease.
Perceptual learning modifies the functional specializations of visual cortical areas (2016)

Training can improve performance of perceptual tasks. This phenomenon, known as perceptual learning, is strongest for the trained task and stimulus, leading to a widely accepted assumption that the associated neuronal plasticity is restricted to brain circuits that mediate performance of the trained task. Nevertheless, learning does transfer to other tasks and stimuli, implying the presence of more widespread plasticity. Here, we trained human subjects to discriminate the direction of coherent motion stimuli. The training effect substantially transferred to noisy motion stimuli. TMS and fMRI measures showed that, before training, visual cortical areas V3A and MT+ made causal and dissociable contributions to the processing of coherent and noisy motion, respectively. After training, the contribution of MT+ to the processing of noisy motion diminished and was superseded by V3A. Our results suggest that learning can modify the inherent functional specializations of visual areas and dynamically reweight their contributions to perceptual decisions. Meeting abstract presented at VSS 2016
An engineered human IgG1 CH2 domain with decreased aggregation and nonspecific binding (2019)

The immunoglobulin (Ig) CH2 domain is a promising scaffold for the development of candidate therapeutics. We have previously shown that the stability of isolated CH2 could be increased by the introduction of an additional disulfide bond and removal of seven N-terminal residues (m01s). However, both isolated CH2 and m01s aggregate, likely due to the existence of aggregation-prone regions (APRs) that we identified by using computational methods. This knowledge was used to generate a phage display library of mutants. The library was incubated at high temperature to remove aggregating CH2 domains, and then panned against a mouse anti-human CH2 monoclonal antibody targeting a conformational epitope to remove misfolded CH2s. After two rounds of panning, one clone, m01s5, with smaller APRs, was identified. After additional mutagenesis one clone, m01s5.4, which aggregated much less than m01s as measured by a turbidity assay and dynamic light scattering, was identified. m01s5.4 also exhibited much lower nonspecific binding than m01s. Engineering of a previously identified m01s-based tumor antigen-specific binder led to a dramatic reduction of its aggregation without affecting its binding. In summary, we describe a new approach for reducing aggregation based on a combination of computational and phage display methodologies, and show that aggregation of CH2-based scaffolds can be significantly reduced by the newly identified mutants, which can improve the developability of potential CH2-based therapeutics.
Protection from Bleomycin‐Induced Pulmonary Injury by Activating A 2A or Inhibiting A 2B Adenosine Receptors (2006)

Pulmonary fibrosis is a fatal side effect of the anti‐neoplastic drug, bleomycin (bleo). Intratracheal injection of bleomycin is used in mice to model idiopathic pulmonary fibrosis since bleo elicits mild transient inflammation followed by progressive fibrosis. Activating the A 2A adenosine receptor inhibits pulmonary macrophage activation and neutrophil chemotaxis, and activation of the A 2B receptor stimulates fibroblast proliferation. This study investigated the effects of the selective A 2A receptor agonist, ATL313 (1.44 μg/kg/day), or the selective A 2B receptor antagonist, ATL851 (10 mg/kg/day), on bleo (0.05 U)‐induced inflammatory cell accumulation in the bronchoalveolar lavage fluid at 72 hours, or pulmonary fibrosis at 2 weeks. Drugs were administered by subcutaneous Alzet minipumps implanted 1 day prior to bleo treatment. ATL313 reduced bleo‐induced inflammation at 72 hours, and either ATL313 or ATL851 enhanced 2‐week survival and reduced pulmonary collagen deposition and alveolar damage at 2 weeks. ATL851 blocked release of the pro‐fibrotic cytokine IL‐6 from isolated murine pulmonary fibroblasts stimulated with the adenosine agonist N ‐ethylcarboxamidoadenosine. On the basis of these data we speculate that pulmonary fibrosis in response to bleo is triggered by an early inflammatory event that is attenuated by activation of A 2A receptors and progresses in part due to adenosine‐mediated activation of A 2B receptors that stimulate mitogenic cytokine release from fibroblasts and possibly other pulmonary cells. NIH grant #P01 HL073361
Design Optimization of a Fully-Compliant Bistable Micro-Mechanism (2001)

Abstract Bistable behavior is desirable for a variety of applications because power is applied only during switching, and the mechanism state remains the same regardless of any power interruptions. The low variability in the stable positions also makes accurate open-loop control of many systems possible, and the precise switching characteristics make them valuable in sensing arrays. In this paper, fully-compliant bistable micromechanisms were modeled using finite elements. This model was then coupled with an optimization program, allowing extensive exploration of the design space. Three designs within this space were generated by minimizing the layout size of the devices subject to force constraints. These designs were subsequently manufactured and tested to verify bistability, with each mechanism snapping as expected between the two stable positions. The design space was then further explored to determine the behavior of the device as the maximum force output increased. This study revealed that the minimum layout size increases with the maximum force output.
Effect of capping groups at the N- and C-termini on the conformational preference of α,β-peptoids (2011)

A graphical abstract is available for this content
A study of switching probability for one spin magnetic particles (2005)

This paper presents a study of the probability of switching for one spin magnetic particle coming from the consideration that the reversal mechanism is given by coherent rotation of the individual atomic spins coupled through strong exchange interactions. A thin film element having in-plane anisotropy is considered. The probability of switching of the magnetic moment against the value of the applied field is computed and the dependence of the certainty of switching against the time window of the applied field is studied. Anisotropy, magnetization and damping parameter are also determined.
Discovery of a Selective Allosteric M1Receptor Modulator with Suitable Development Properties Based on a Quinolizidinone Carboxylic Acid Scaffold (2011)

One approach to ameliorate the cognitive decline in Alzheimer's disease (AD) has been to restore neuronal signaling from the basal forebrain cholinergic system via the activation of the M(1) muscarinic receptor. A number of nonselective M(1) muscarinic agonists have previously shown positive effects on cognitive behaviors in AD patients, but were limited due to cholinergic adverse events thought to be mediated by the activation of the M(2) to M(5) subtypes. One strategy to confer selectivity for M(1) is the identification of positive allosteric modulators, which would target an allosteric site on the M(1) receptor rather than the highly conserved orthosteric acetylcholine binding site. Quinoline carboxylic acids have been previously identified as highly selective M(1) positive allosteric modulators with good pharmacokinetic and in vivo properties. Herein is described the optimization of a novel quinolizidinone carboxylic acid scaffold with 4-cyanopiperidines being a key discovery in terms of enhanced activity. In particular, modulator 4i gave high plasma free fractions, enhanced central nervous system (CNS) exposure, was efficacious in a rodent in vivo model of cognition, and afforded good physicochemical properties suitable for further preclinical evaluation.
Evaluating physically unclonable functions on a large set of FPGAs (2016)

Detailed knowledge of the impact of environmental factors on Physically Unclonable Functions (PUFs) is required for designing secure and reliable chips and extract uniqueness from them. This knowledge can be obtained only by analyzing the behavior of PUF designs over a large number of devices while varying temperature and supply voltage. Such analysis is still missing in the open literature, since the majority of the works report evaluations carried out either on a limited number of devices or in too few environmental conditions. In this work, we present an exhaustive characterization of two PUFs constructions suitable for FPGAs: a ring oscillator PUF and a timing path violation PUF. Both constructions were tested on 52 FPGAs produced by Xilinx, at temperatures ranging from 10°C to 70°C and applying voltages ranging from 0.95 to 1.05 V. Our experiments quantify the uniqueness of each construction, demonstrate their limited sensitivity to temperature variations, and show the linear impact that voltage variations have on both PUFs. Our results are a crucial step towards the design of reliable PUFs for reconfigurable devices and their widespread use as secure building blocks.
A comparison of classification methods for local binary patterns (2016)

Texture recognition is an important tool used for content-based image retrieval, face recognition, and satellite image classification applications. One of the most successful features for texture recognition is local binary patterns (LBP), which computes local intensity differences for a pixel with respect to its neighbor pixels. In many studies in the literature, histogram based similarity measures are employed to classify LBP features. In this study, we investigate the performance of support vector machines, linear discriminant analysis, and linear regression classifier to improve the success of LBP features. We achieved 84.4% classification success using linear regression classification.
Mechanism of Repair of Acrolein- and Malondialdehyde-Derived Exocyclic Guanine Adducts by the α-Ketoglutarate/Fe(II) Dioxygenase AlkB (2014)

The structurally related exocyclic guanine adducts α-hydroxypropano-dG (α-OH-PdG), γ-hydroxypropano-dG (γ-OH-PdG), and M1dG are formed when DNA is exposed to the reactive aldehydes acrolein and malondialdehyde (MDA). These lesions are believed to form the basis for the observed cytotoxicity and mutagenicity of acrolein and MDA. In an effort to understand the enzymatic pathways and chemical mechanisms that are involved in the repair of acrolein- and MDA-induced DNA damage, we investigated the ability of the DNA repair enzyme AlkB, an α-ketoglutarate/Fe(II) dependent dioxygenase, to process α-OH-PdG, γ-OH-PdG, and M1dG in both single- and double-stranded DNA contexts. By monitoring the repair reactions using quadrupole time-of-flight (Q-TOF) mass spectrometry, it was established that AlkB can oxidatively dealkylate γ-OH-PdG most efficiently, followed by M1dG and α-OH-PdG. The AlkB repair mechanism involved multiple intermediates and complex, overlapping repair pathways. For example, the three exocyclic guanine adducts were shown to be in equilibrium with open-ring aldehydic forms, which were trapped using (pentafluorobenzyl)hydroxylamine (PFBHA) or NaBH4. AlkB repaired the trapped open-ring form of γ-OH-PdG but not the trapped open-ring of α-OH-PdG. Taken together, this study provides a detailed mechanism by which three-carbon bridge exocyclic guanine adducts can be processed by AlkB and suggests an important role for the AlkB family of dioxygenases in protecting against the deleterious biological consequences of acrolein and MDA.