gebhart/patrepeval huggingface dataset:
Engineered protein-small molecule conjugates empower selective enzyme inhibition (2021)

S ummary Specific, potent ligands drive precision medicine and fundamental biology. Proteins, peptides, and small molecules constitute effective ligand classes. Yet greater molecular diversity would aid the pursuit of ligands to elicit precise biological activity against challenging targets. We demonstrate a platform to discover protein-small molecule (PriSM) hybrids to combine unique pharmacophore activities and shapes with constrained, efficiently engineerable proteins. A fibronectin protein library was yeast displayed with a single cysteine coupled to acetazolamide via a maleimide-poly(ethylene glycol) linker. Magnetic and flow cytometric sorts enriched specific binders to carbonic anhydrase isoforms. Isolated PriSMs exhibited potent, specific inhibition of carbonic anhydrase isoforms with superior efficacy to acetazolamide or protein alone including an 80-fold specificity increase and 9-fold potency gain. PriSMs were engineered with multiple linker lengths, protein conjugation sites, and sequences against two different isoforms, which reveals platform flexibility and impacts of molecular designs. PriSMs advance the molecular diversity of efficiently engineerable ligands.
Strategies for Fragment Library Design (2016)

Many fragment libraries are chemically diverse and have been selected based on a good balance of properties. However, they all tend to have limited three-dimensional diversity. While significant effort has been expended in improving the profiles of HTS libraries, relatively little has been published concerning the introduction of three-dimensionality into fragment screening collections. Introducing a descriptor of shape for fragment molecules will add another degree of diversity to the fragment library, not only providing more choice when selecting molecules to optimize but also offering different opportunities when screening against “old” and “new” targets such as protein-protein interactions (PPI) where complementarity to a three-dimensional interface of one protein may be important in disrupting its interaction with a partner protein. This chapter discusses authors' efforts toward this goal. The Beatson Drug Discovery Programme (BDDP) fragment screening collection currently consists of 1014 compounds that conform to the well-established guidelines for selecting fragment molecules.
Design of a 2-Bit Sigma-Delta Modulator for Scintillation Waveform Capture (2017)

Sigma-delta modulation is a common technique used in analog-to-digital conversion. It has been shown that it can be implemented in a field-programmable gate array (FPGA) using minimal external analog components. Zhao et al. demonstrated that energy of scintillation pulses can be computed by adding up all the elements on the output from a conventional 1-bit sigmadelta modulator. However, for parameters selected for a suitable resolution and dynamic range, the system passes through a period of saturation. During saturation, information about the shape of the pulse is lost even though the integrated energy remains preserved. We present the design of a 2-bit version of the sigmadelta modulator that makes use of a nonlinear adaptive digital-to-analog converter (DAC) that keeps the system unsaturated. Each output bit is scaled by one of the four possible values the DAC can take, resulting in a 2-bit modulation. We have demonstrated that the 2-bit modulation retains information about the pulse shape.
Recovery of nickel and cobalt from nickel laterite leach solution using chelating resins and pre‐reducing process (2018)

Abstract The aim of this work was to recover nickel and cobalt from a nickel laterite leach solution using chelating resins combined with a pre‐reducing process. Sodium sulphite was used as a reducing agent to convert Fe(II) from Fe(III) and increase adsorption efficiency. Batch experiments were performed using synthetic solutions to study the effect of pH in recovering these metals using chelating resins Lewatit TP 207 and Lewatit TP 220. Column experiments were performed to simulate the fixed‐bed column process in the following two steps: first, removing copper; and second, recovering nickel and cobalt. Two acids were tested as eluent, namely, sulphuric and hydrochloric acid 1M and 2M. Batch experiments showed that increasing the recovery of the metals accompanied an increase in pH. Copper recovery was maximal at pH 2.00, and the resin selectivity changed in pH above 2, decreasing copper adsorption. However, batch experiments showed that nickel and cobalt recovery was higher at pH 3.50, and resin adsorbed a high concentration of contaminants such as iron, zinc, and chromium. For this reason, nickel and cobalt recovery at pH 2.00 was better in column experiments, with less of the contamination in the metals being adsorbed by the resin and a high selectivity for nickel and cobalt. Hydrochloric acid 2M showed to be more efficient as eluent than sulphuric acid. A precipitation process using NaOH was used to remove contaminants present in the eluent solution, and Cyanex 272 was used to separate cobalt and nickel through the solvent extraction process.
Abstract 2993: Unmutated tumor antigens are abundant and contribute to tumor control in melanoma (2023)

Abstract Recognition of MHC-I-associated tumor antigens (TAs) by CD8+ T cells is central to antitumor immunity. Owing to the elevated tumor mutational burden (TMB) in melanoma, the marked efficacy of immune checkpoint blockade (ICB) has been attributed to the recognition of mutated TAs. However, recent reports showed that response to ICB in melanomas with low TMB is associated with CD8+ T-cell reactivity against melanocyte lineage-associated antigens (LSAs). Here, we systematically evaluated the contribution of all TA classes, i.e., mutated and unmutated, canonical and non-canonical, to the antigenic landscape of melanoma. We characterized the TAs from melanoma biopsies and patient-derived cell lines using proteogenomics. Out of 79450 MHC-I-associated peptides (MAPs) identified from 19 samples, we found 557 unmutated TAs classified as tumor-specific (TSA), tumor-associated (TAA), or LSAs. These TAs most often derived from annotated open-reading frames, followed by ncRNAs and intergenic regions. By contrast, only 6 MAPs were mutated and tumor-specific, which could be partially explained by a decreased expression of mutations within MAP-generating genomic regions. While the number of unmutated TAs with predicted presentation (TApres) in melanoma patients was similar between responders and non-responders pre-ICB, non-responders showed marks of inefficient antigen presentation. In consequence, only responders lost TApres upon treatment, in tandem with an expansion in tumor-infiltrating lymphocytes. These results reveal a previously underappreciated contribution of unmutated TAs to tumor control in melanoma and suggest that enhancing their recognition could improve the ICB efficacy in non-responders. Citation Format: Anca Apavaloaei, Qingchuan Zhao, Leslie Hesnard, Krystel Vincent, Marie-Pierre Hardy, Chantal Durette, Joël Lanoix, Jean-Philippe Laverdure, Jean-David Larouche, Maria Virginia Ruiz Cuevas, Grégory Ehx, Sébastien Lemieux, Pierre Thibault, Claude Perreault. Unmutated tumor antigens are abundant and contribute to tumor control in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2993.
High-Speed InAs Quantum-Dot Electrooptic Phase Modulators (2011)

In this letter, we report results of direct current (dc) and radio-frequency (RF) characteristics of self-assembled InAs quantum-dot (QD) electrooptic modulators. Although dc modulation results have been reported in the literature, these are the first high-frequency designs and measurements. These QD modulator wafers were grown by molecular beam epitaxy (MBE) and phase modulator devices were fabricated with coplanar traveling-wave electrodes. For the 800-μm-long modulators, the half-wave voltage V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">π</sub> was measured as 11.4 V at 1.55 μm and 7.34 V at 1.32 μm. The phase variation is 21.9°/(mm·V). The linear electrooptic coefficient T <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">41</sub> is calculated to be 35.4 pm/V for QDs. These modulators have a 3-dB bandwidth of 10 GHz. A signal-to-noise ratio of 9 dB was measured at 20 GHz.
Correlation of Microstructure and Transport Properties of Multilayered Graphene Spin Valves on SiO2/Si (2013)

Multi-layered graphene based spin valves were deposited on SiO2/Si substrates and the Co ferromagnetic and non-magnetic electrodes were patterned using electron-beam lithography. Aberration-corrected (scanning) transmission electron microscopy imaging and energy dispersive X-ray spectroscopy were employed to study the interfacial structure of the device components from thin cross-sectional lamellae obtained by focused ion beam microscopy. The robustness of the spin injection with a constant spin polarization under positive and negative bias voltage was attributed to the interface smoothness which leads to suppression of spin scattering at the interface between the ferromagnet and the multi-layered graphene.
Effects of Transvenous Electrode Polarity and Waveform Duration on the Relationship Between Defibrillation Threshold and Upper Limit of Vulnerability (1997)

The almost identical changes in ULV and DFT with changes in electrode polarity and waveform duration provide new evidence to support the ULV hypothesis of defibrillation.
Supplementary Figures S1-S5 from ITPR1 Protects Renal Cancer Cells against Natural Killer Cells by Inducing Autophagy (2023)

&lt;p&gt;Supplementary Figures S1-S5. Figure S1. Differential susceptibility of 786-0, PRC3, and WT7 cell lines to NK-mediated lysis. Figure S2. Role of ANGPTL4 and ADM in RCC cell susceptibility to NK-mediated lysis. Figure S3. VHL and NK ligand expression in RCC cells. Figure S4. Silencing of HIF-2α and NK ligand expression in 786-0 cells. Figure S5. VHL status, targeting of HIF-2α or silencing of ITPR1 does not regulate autophagy in 786-0 cells.&lt;/p&gt;
Fully Sequential and Distributed Dynamic Algorithms for Minimum Spanning Trees (2000)

In this paper, we present a fully-dynamic distributed algorithm for maintaining a minimum spanning tree on general graphs with positive real edge weights. The goal of a dynamic MST algorithm is to update efficiently the minimum spanning tree after dynamic changes like edge weight changes, rather than having to recompute it from scatch each time. The first part of the paper surveys various algorithms available today both in sequential and distributed environments to solve static MST problem. We also present some of the efficient sequential algorithms for computing dynamic MST like the Frederickson's algorithm and Eppstein's sparsification technique. Lastly we present our new sequential and distributed algorithms for dynamic MST problem. To our knowledge, this is the first of the distributed algorithms for computing dynamic MSTs.
Preparation and characterization of LiNbO3 thin films produced by chemical-vapor deposition (1995)

Lithium niobate [LiNbO3 (LN)] thin films with good surface morphology and crystallinity have been epitaxially grown on lithium tantalate [LiTaO3 (LT)] substrates by chemical-vapor deposition using lithium dipivaloylmethane [Li(C11H19O2)] and niobium pentaethoxide [Nb(OC2H5)5] without postannealing. The Li/Nb ratio of LN thin films was easily controlled by adjusting the Nb source temperature, and it is possible to prepare LN thin films with stoichiometric composition (Li/Nb=1). The crystallinity of LN thin films greatly depends on substrate temperature and surface orientation of the LT substrate. It becomes better with increasing substrate temperature and is equivalent to a single crystal at 700 °C. It also becomes better in the order of (012), (110), and (001) planes of the LT substrate. The properties of surface acoustic wave propagation can be improved by preparing the LN thin film on the LT substrate. The electromechanical coupling factor k2 of LN/(012)LT is 0.52%, and is greater than that of the (012)LT substrate alone, 0.081%. The sound velocity of LN/(012)LT calculated from the central resonant frequency is 3200 m/s, and this value is greater than that of the (012)LT substrate by itself, 3140 m/s.
Self‐Organizing Properties of Monosubstituted Sucrose Fatty Acid Esters: The Effects of Chain Length and Unsaturation (2006)

Three families of mono-substituted sucrose fatty acid esters were prepared by enzymatic and classical synthetic procedures, and their self-assembly and self-organizational properties were investigated by thermal polarised light microscopy, differential scanning calorimetry and X-ray diffraction. The properties were evaluated as a function of the fatty acid chain length. For the lower homologues of the series columnar liquid-crystalline stacking structures were found, whereas for the higher homologues, lamellar phases predominated. A model for the columnar stacking arrangement, consisting of a unique arrangement of the molecules which could lead to the creation of multiple internal ion channels between the hydrophobic interior and the hydrophilic exterior of the columns, is suggested.
Dipole-induced self-assembly of helical β-peptides (2008)

In this work, the interactions between beta-peptides are investigated for helix-forming peptides using molecular simulation. The role of electrostatic interactions in the self-assembly of these peptides is studied by calculating the dipole moment of various 14-helical beta-peptides using molecular dynamics simulations. The stability of a beta-peptide that is known to form a liquid crystalline phase is determined by calculating the potential of mean force using the expanded ensemble density of states method. This peptide is found to form a mechanically stable 14-helix in an implicit solvent model. The interaction between two of these peptides is examined by calculating the potential of mean force between the two peptides in implicit solvent. The peptides are shown to favorably associate in an end-to-end manner, driven largely by dipolar interactions. In order to understand the possible structures that form when many peptides interact in solution, a coarse-grained model is developed. Brownian dynamics simulations of the coarse-grained model at intermediate concentrations (1-50 mM) are performed, and the aggregation behavior is understood by calculating the diffusivity and the radial distribution function. An analysis of the resultant structures reveals that the coarse-grained model of the peptide leads to the formation of spherical clusters.
Chiral Resolution and Pharmacological Characterization of the Enantiomers of the Hsp90 Inhibitor 2‐Amino‐7‐[4‐fluoro‐2‐(3‐pyridyl)phenyl]‐4‐methyl‐7,8‐dihydro‐6H‐quinazolin‐5‐one Oxime (2014)

Heat-shock protein 90 (Hsp90) is a molecular chaperone involved in the stabilization of key oncogenic signaling proteins, and therefore, inhibition of Hsp90 represents a new strategy in cancer therapy. 2-Amino-7-[4-fluoro-2-(3-pyridyl)phenyl]-4-methyl-7,8-dihydro-6H-quinazolin-5-one oxime is a racemic Hsp90 inhibitor that targets the N-terminal adenosine triphosphatase site. We developed a method to resolve the enantiomers and evaluated their inhibitory activity on Hsp90 and the consequent antitumor effects. The (S) stereoisomer emerged as a potent Hsp90 inhibitor in biochemical and cellular assays. In addition, this enantiomer exhibited high oral bioavailability in mice and excellent antitumor activity in two different human cancer xenograft models.
Preparing for Highly Scalable and Replicable IoT Systems (2020)

Interoperability, reusability, and scalability are important design objectives as IoT systems become pervasive and begin to address complex use cases. They underpin the need for open-standard solutions which allow vendors and solution providers to collaborate. A horizontal architecture satisfies the three design objectives while breaking down the barriers between silo IoT applications. oneM2M, the global IoT standard, defines such a horizontal architecture. It consists of a middleware technology layer located between a lower layer that consists of devices and communications technologies, and an upper layer of IoT applications. This article describes the oneTRANSPORT Data Marketplace pilot project, based on the oneM2M standard. It enabled IoT data sharing from over 200 types of connected assets belonging to several public and private sector agencies. Through practical trials, the pilot illustrates how data scientists, operations staff, and facilities managers supervised transportation networks and offered real-time journey planning guidance to the traveling public. The value of the oneM2M standards-based data marketplace is illustrated by reference to other deployments that reuse the horizontal architecture over a larger geographic footprint and to implement other IoT use cases.
How Did AQ Face The East-West Challenge? An Analysis of the AQ Family's Performance in the 2nd International Competition of Machine Learning Programs (1995)

The “East-West Challenge” is the title of the second international competition of machine learning programs, organized in the Fall 1994 by Donald Michie, Stephen Muggleton, David Page and Ashwin Srinivasan from Oxford University. The goal of the competition was to solve the “TRAINS problems”, that is to discover the “simplest” classification rules for train-like structured objects. The rule complexity was judged by a Prolog program that counted the number of various components in the rule expressed in the from of Prolog Horn clauses. There were 65 entries from several countries submitted to the competition. The GMU team’s entry was generated by three members of the AQ family of learning programs: AQ-DT, INDUCE and AQ17-HCI. The paper analyses the results obtained by these programs and compares them to those obtained by other learning programs. It also presents ideas for further research that were inspired by the competition. One of these ideas is a challenge to the machine learning community to develop a measure of knowledge complexity that would adequately capture the “cognitive complexity” of knowledge. A preliminary measure of such cognitive complexity, called C-complexity, different from the Prologcomplexity (P-complexity) used in the competition, is briefly discussed.
Abstract 11: A Novel Tissue Engineered Three-Dimensional Biomimetic Platform for In Vitro Study of BIA-ALCL (2019)

PURPOSE: Implicated in at least 16 deaths worldwide and with a lifetime risk estimated by some as high as 1 in 4000 cases of textured device implantation, breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) has garnered increasing attention from researchers and the lay press alike. However, largely because of the lack of appropriate models, the pathogenesis of this devastating complication remains poorly understood. We have developed a tissue engineered three-dimensional biomimetic breast tissue platform that utilizes patient derived tissues in order to study BIA-ALCL. METHODS: Patient-derived breast tissue was processed, and all cellular constituents including adipocytes, organoids, and stromal vascular fraction (including immune cells) were used to populate an approximately 50μL three-dimensional type I collagen extracellular matrix within 96 well plates. Two separate experiments were then performed. First, BIA-ALCL cells were seeded at a density of 200,000 cells/mL homogenously within the biomimetic platform and also in wells that contained 0.3% collagen alone without patient-derived breast cells. In addition, BIA-ALCL cells were mixed with collagen at a density of 40,000/μL and fabricated into 1μL “tumor buttons” and placed onto the bottom of each well. These buttons were then immersed within either biomimetic breast platform or 0.6% collagen-only matrix. Wells were then imaged every other day using confocal microscopy, and images were processed using Imaris™ software, analyzing for cell counts in the first experiment and for tumor cell invasion into the surrounding environment for the second experiment. RESULTS: In the first experiment, BIA-ALCL cells thrived in the biomimetic platform and grew significantly more rapidly than their counterparts in the collagen-only wells. Both groups started at an equal density of approximately 300 cells per three-dimensional confocal snapshot on day 0, and both groups demonstrated logistic growth curves. However, cells in the biomimetic platform grew nearly 50% faster and reached a higher plateau than those in the collagen-only group. On day 10 the mean cell number in the biomimetic group was 596 ± 40.8 versus 432.2 ± 32.6 in the collagen only group (p<0.0001). Analysis of the tumor buttons showed multiple instances of invasion of BIA-ALCL cells into both the surrounding biomimetic breast platform and the collagen-only matrix as early as day two and as late as day twelve. Cells traveled up to hundreds of microns into the surrounding environment in some cases. CONCLUSIONS: We have developed the first tissue engineered three-dimensional biomimetic in vitro model of BIA-ALCL to date. We believe that this novel in vitro system will allow for a better mechanistic understanding of BIA-ALCL and may eventually aid in the discovery of methods to prevent this rare, poorly understood, and potentially fatal complication of breast prosthesis placement.