gebhart/patrepeval huggingface dataset:
AGS62P1, a Novel Anti-FLT3 Antibody Drug Conjugate, Employing Site Specific Conjugation, Demonstrates Preclinical Anti-Tumor Efficacy in AML Tumor and Patient Derived Xenografts (2015)

Abstract FLT3 (FMS-like tyrosine kinase 3) is a member of the class III receptor tyrosine kinase family, which is highly expressed in the blasts of both AML and ALL patients. In addition to FL ligand stimulation, FLT3 can also be activated by two distinct clusters of mutations: internal tandem duplications (FLT3/ITDs) in 20% to 25% patients and point mutations at position D835 in the tyrosine-kinase domain (FLT3/TKD) in 7% to 10% patients. FLT3 tyrosine kinase inhibitors (TKI) are mainly active against FLT3 mutant AML. An antibody drug conjugate (ADC), directed against the extracellular domain of FLT3 may only require FLT3 cell surface expression independent of mutation status. The restricted cellular distribution of FLT3 receptor and a higher expression in AML than in normal bone marrow makes FLT3 a favorable ADC target. Therefore, this ADC based strategy may offer a therapeutic alternative for AML patients independent of FLT3 status. Here, we report the preclinical assessment of a novel FLT3 targeting ADC, AGS62P1. AGS62P1 consists of a human anti-FLT3 monoclonal antibody, site specifically conjugated to a potent cytotoxic payload. FLT3 expression is confirmed in a large panel of AML and ALL tumor cells as well as in AML patient specimens via flow cytometry. The anti-leukemic activity of AGS62P1 was evaluated against AML and ALL tumor cell lines, in vitro and in vivo. AGS62P1 demonstrated strong binding affinity (0.1-0.5 nM) and potent cytotoxic activity in FLT3/ITD and Non-ITD tumor models, in vitro. Cytotoxic IC50 potency for AGS62P1 was 0.5-13 nM in FLT3/ITD and 0.2-12 nM in FLT3 non-ITD models. A fluorescence based assay confirmed that AGS62P1 is rapidly internalized in AML tumor cell lines. AGS62P1 is highly efficacious in FLT3/ITD and non-ITD tumor xenografts, leading to significant tumor growth inhibition or complete tumor regression. In primary AML patient xenograft drug treatment studies, the engraftment and outgrowth of 5/6 samples were significantly reduced when treated with AGS62P1. Taken together our data demonstrate that AGS62P1 exhibits potent antitumor activity against a broad panel of AML tumor models and primary AML samples, regardless of FLT3 status. We believe AGS62P1 may be an effective and alternative therapeutic for AML patients, which can bypass the TKI mediated resistance and deliver target specific effect through a different mode of action. Disclosures Jin: Agensys: Research Funding. Anand:Agensys: Employment. Dick:Agensys: Research Funding.
Energy-resolved CT imaging with a photon-counting silicon-strip detector (2014)

Photon-counting detectors are promising candidates for use in the next generation of x-ray computed tomography (CT) scanners. Among the foreseen benefits are higher spatial resolution, better trade-off between noise and dose and energy discriminating capabilities. Silicon is an attractive detector material because of its low cost, mature manufacturing process and high hole mobility. However, it is sometimes overlooked for CT applications because of its low absorption efficiency and high fraction of Compton scatter. The purpose of this work is to demonstrate that silicon is a feasible material for CT detectors by showing energy-resolved CT images acquired with an 80 kVp x-ray tube spectrum using a photon-counting silicon-strip detector with eight energy thresholds developed in our group. We use a single detector module, consisting of a linear array of 50 0.5×0.4 mm detector elements, to image a phantom in a table-top lab setup. The phantom consists of a plastic cylinder with circular inserts containing water, fat and aqueous solutions of calcium, iodine and gadolinium, in different concentrations. By using basis material decomposition we obtain water, calcium, iodine and gadolinium basis images and demonstrate that these basis images can be used to separate the different materials in the inserts. We also show results showing that the detector has potential for quantitative measurements of substance concentrations.
Impedimetric Monitoring of Cell‐Based Assays (2015)

Abstract Electrochemical impedance measurements (electric cell‐substrate impedance sensing, ECIS) have been established as a label‐free and noninvasive experimental tool to monitor and quantify the behaviour of adherent cells grown on planar gold‐film electrodes while they are exposed to chemical, biological or physical stimuli/stressors. Owing to the noninvasiveness of the measurement, impedance‐based cell observation provides continuous information about the cell response in real time. Different data acquisition modes in combination with tailored electrode layouts are used to assess the time courses of several fundamental processes in cell physiology such as cell adhesion, cell proliferation, cell migration, intracellular signal transduction or cell death. Experiments are performed entirely automated and computer‐controlled under regular cell culture conditions. State‐of‐the‐art instrumentation allows for the parallel analysis of up to 384 samples. Its multimodality and throughput suggest that ECIS can play a similar role for the analysis of cell‐based assays as flow cytometry. Key Concepts Electric cell‐substrate impedance sensing (ECIS) is a noninvasive experimental technique to monitor adherent cells in vitro along different types of biomedical or bioanalytical assays with a time resolution that is adjustable from milliseconds to hours. To perform ECIS‐based assays, the cells are grown on planar gold‐film electrodes deposited on the surface of a regular cell culture dish. ECIS is compatible with regular cell culture conditions, fully automated and software controlled. The approach is sensitive to (1) the fractional coverage of the electrode surface and (2) the three‐dimensional shape of the cells attached to the electrode. ECIS is significantly more sensitive for cell shape changes than optical microscopy. On the basis of this generic sensitivity, different assays have been developed to monitor cell adhesion to biomaterial surfaces, cell proliferation, cell migration, cell death or the stimulation of cell‐surface receptors. The scope of available assay formats has been further extended using elevated electric fields for well‐defined cell manipulation integrated into continuous, impedance‐based cell monitoring (e.g. in situ electroporation).
Gain to Absorption Ratio of Self-Induced Transparency Modelocked Quantum Cascade Lasers (2011)

A model to calculate the gain to absorption ratio of self-induced transparency modelocked quantum cascade lasers is presented and then used to find the gain to absorbing periods ratio that is required for stable operation.
Dye-Sensitized Solar Cells Consisting of 3D-Electrodes—A Review: Aiming at High Efficiency From the View Point of Light Harvesting and Charge Collection (2010)

Directions to high efficiency dye-sensitized solar cells (DSCs) are reviewed in terms of light harvesting and charge collection. Three dimensional DSCs characterized by a double dye layer electrode, a floating electrode, and a fiber type electrode are proposed. The potentiality of each structure was discussed by using each model cell. Transparent conductive layerless electrodes were the key structures in these cells. Fabrication processes and fundamental performances are reported. Finally, it is concluded that dyes having high photoconversion efficiency in the near IR and IR regions are essential for realizing these tandem and hybrid cells.
Tradeoffs in power-efficient issue queue design (2002)

A major consumer of microprocessor power is the issue queue. Several microprocessors, including the Alpha 21264 and POWER4TM, use a compacting latch-based issue queue design which has the advantage of simplicity of design and verification. The disadvantage of this structure, however, is its high power dissipation.In this paper, we explore different issue queue power optimization techniques that vary not only in their performance and power characteristics, but in how much they deviate from the baseline implementation. By developing and comparing techniques that build incrementally on the baseline design, as well as those that achieve higher power savings through a more significant redesign effort, we quantify the extra benefit the higher design cost techniques provide over their more straightforward counterparts.
Design and Evaluation of a Near-Infrared Dispersive Spectrometer That Uses a He-Ne Laser for Automatic Internal Wavelength Calibration (2002)

A diffraction-grating near-infrared spectrometer that uses a He–Ne laser for automatic internal wavelength calibration is described. The instrument uses the known location of the higher diffraction orders of the 632.8-nm laser line to perform wavelength calibration in the near-infrared region. The wavelength accuracy of the dispersive spectrometer was compared with that of a Fourier transform near-infrared spectrometer whose wavelength scale was validated by calibration with the known spectrum of ethyne. The average absolute wavelength deviation between the two spectrometers for four isolated bands of trichloromethane was found to be +0.12 nm. The average values of the wavelengths of four isolated bands of trichloromethane obtained with the two spectrometers used in this study were determined to be: 1151.62 ± 0.28 nm (3 ν 1 ), 1410.74 ± 0.52 nm (2 ν 1 + ν 4 ), 1692.38 ± 0.49 nm (2 ν 1 ), and 1860.20 ± 0.16 nm ( ν 1 + 2 ν 4 ).
Ruthenium alkylidene complexes coordinated with tricyclohexylphosphine and heterocyclic N-donor ligands (2003)

Reactions of the bis(tricyclohexylphosphine) ruthenium alkylidene complexes (PCy 3 ) 2 (Cl) 2 -Ru=CHPh, (PCy 3 ) 2 (Cl) 2 Ru=CHCH=CPh 2 , and (PCy 3 ) 2 (Cl) 2 Ru=CHCH=CMe 2 with excess pyridine (py) cleanly furnish the six-coordinate bis(pyridine) derivatives (PCy 3 )(py) 2 (Cl) 2 -Ru=CHPh, (PCy 3 )(py) 2 (Cl) 2 Ru=CHCH=CPh 2 , and (PCy 3 )(py) 2 (Cl) 2 Ru=CHCH=CMe 2 , respectively. In solution, there is evidence for an equilibrium between (PCy 3 )(py) 2 (Cl) 2 -Ru=CHPh and a five-coordinate mono(pyridine) derivative, (PCy 3 )(py)(Cl) 2 Ru=CHPh. This mono(pyridine) complex can be isolated by heating (PCy 3 )(py) 2 (Cl) 2 Ru=CHPh in toluene under dynamic vacuum to remove dissociated pyridine as a toluene azeotrope. The diphenylvinylcarbene complex (PCy 3 )(py) 2 (Cl) 2 Ru=CHCH=CPh 2 has been structurally characterized by X-ray diffraction, and it exhibits a vinylcarbene ligand tilted by ~30 with respect to the Cl(1)-Ru-Cl(2)-C(1) plane. In addition, the Ru-N bond located trans to the vinylcarbene is elongated by a substantial 0.136(2) in comparison to the Ru-N bond located trans to the tricyclohexylphosphine. The dimethyl-vinylcarbene derivative (PCy 3 )(py) 2 (Cl) 2 Ru=CHCH=CMe 2 can be isolated as well, but it decom-poses rapidly when redissolved. Surprisingly, reaction of (PCy 3 ) 2 (Cl) 2 Ru=CHPh with 1-methyl-imidazole (1-MeIm) follows a different route and provides the cationic tris(imidazole) product [(PCy 3 )(1-MeIm) 3 (Cl)Ru=CHPh][Cl], which also has been structurally characterized. These new compounds are interesting examples of ruthenium alkylidene complexes coordinated with hetero-cyclic N-donor ligands, but they display mediocre catalytic activity for the ring-closing metathesis of diethyl diallylmalonate.
Intelligent Multiobjective Optimization of Distribution System Operations (2006)

A hybrid fuzzy knowledge-based system with crisp and fuzzy rules as well as numerical methods was developed for multiobjective optimization of power distribution system operation. The development process and knowledge-acquisition process for the fuzzy knowledge-based system are described in detail. Fuzzy sets are defined for recent temperature trend, line section loading, transformer aging, voltage-level guidelines, and the degree of desirability of a proposed switching combination. After a heuristic preprocessor proposes a list of switch openings that would seem to reduce system losses, network radiality rules consider whether to open a particular switch and find a corresponding switch that can be closed to maintain radiality. Network parameter rules determine whether the proposed switching combination will violate network integrity. Network performance rules find the degree of desirability of proposed switching combinations for enhancing multiple objectives. All operational aspects of power distribution systems are considered, and a solution is still found in real time.
Dilution of oral D<sub>3</sub>‐Creatine to measure creatine pool size and estimate skeletal muscle mass: development of a correction algorithm (2018)

The D<sub>3</sub> -Cr dilution method is further validated here as a non-invasive, easy-to-use test for measuring muscle mass. The technical issue of D<sub>3</sub> -Cr spillage can be corrected for with a simple algorithm based on fasting spot urine samples. Muscle mass by Cr dilution potentially has broad applications in clinical and research settings.
Nanoparticle Assemblies in Thin Films of Supramolecular Nanocomposites (2012)

We demonstrated a versatile approach to obtain layered nanoparticle sheets with in-plane hexagonal order and 3-D ordered arrays of single nanoparticle chains in thin films upon blending nanoparticles with block copolymer (BCP)-based supramolecules. Basic understanding on the thermodynamic and kinetic aspects of the assembly process paved a path to manipulate these assemblies to meet demands in nanoparticle-based device fabrication and understand structure-property correlations.
Single-Dose Assay Technique for Variola Virus (1964)

A biological assay for variola virus was needed that would (i) require a minimum of time and (ii) have acceptable precision. Preliminary titrations made in 11-day-old embryonated eggs and in suckling mice (6 to 24 hr of age) demonstrated a linear relationship between the concentration of variola virus injected and the mean reciprocal time to death (MTD) of both hosts. This linear response indicated that the injection of a single dose of virus suspension and the measurement of the MTD should result in an acceptable assay method. Seven replicate samples of liquid preparations (20% chorioallantoic membrane in Heart Infusion Broth) and the freeze-dried material obtained with these suspensions were assayed in triplicate for pock infectious units and for MTD. The variance of the pock counts was far greater than was expected from a Poisson distribution, and coefficients of variation ranged from 25 to 61%. Variances obtained with the single-dilution assay were all far below that expected from a Poisson distribution, and coefficients of variations ranged from 5.2 to 13.6%. The use of the MTD assay resulted in a saving of time, a saving in the number of hosts necessary per assay, and increased precision.
Gait Recognition via Disentangled Representation Learning (2019)

Gait, the walking pattern of individuals, is one of the most important biometrics modalities. Most of the existing gait recognition methods take silhouettes or articulated body models as the gait features. These methods suffer from degraded recognition performance when handling confounding variables, such as clothing, carrying and view angle. To remedy this issue, we propose a novel AutoEncoder framework to explicitly disentangle pose and appearance features from RGB imagery and the LSTM-based integration of pose features over time produces the gait feature. In addition, we collect a Frontal-View Gait (FVG) dataset to focus on gait recognition from frontal-view walking, which is a challenging problem since it contains minimal gait cues compared to other views. FVG also includes other important variations, e.g., walking speed, carrying, and clothing. With extensive experiments on CASIA-B, USF and FVG datasets, our method demonstrates superior performance to the state of the arts quantitatively, the ability of feature disentanglement qualitatively, and promising computational efficiency.
Development of New Conjugated Polymers with Donor−π-Bridge−Acceptor Side Chains for High Performance Solar Cells (2009)

Two new conjugated polymers have been designed and synthesized for polymer solar cells. Both of them exhibit excellent photovoltaic properties with a power conversion efficiency as high as 4.74%. Different from the traditional linear donor-acceptor (D-A) type conjugated polymers, these newly designed polymers have a two-dimensional conjugated structure with their tunable acceptors located at the end of D-A side chains and connected with the donors on the main chain through an efficient pi-bridge. This approach provides great flexibility in fine-tuning the absorption spectra and energy levels of the resultant polymers for achieving high device performance.
Peptide-Based Optical uPAR Imaging for Surgery: In Vivo Testing of ICG-Glu-Glu-AE105 (2016)

Near infrared intra-operative optical imaging is an emerging technique with clear implications for improved cancer surgery by enabling a more distinct delineation of the tumor margins during resection. This modality has the potential to increase the number of patients having a curative radical tumor resection. In the present study, a new uPAR-targeted fluorescent probe was developed and the in vivo applicability was evaluated in a human xenograft mouse model. Most human carcinomas express high level of uPAR in the tumor-stromal interface of invasive lesions and uPAR is therefore considered an ideal target for intra-operative imaging. Conjugation of the flourophor indocyanine green (ICG) to the uPAR agonist (AE105) provides an optical imaging ligand with sufficiently high receptor affinity to allow for a specific receptor targeting in vivo. For in vivo testing, human glioblastoma xenograft mice were subjected to optical imaging after i.v. injection of ICG-AE105, which provided an optimal contrast in the time window 6-24 h post injection. Specificity of the uPAR-targeting probe ICG-AE105 was demonstrated in vivo by 1) no uptake of unconjugated ICG after 15 hours, 2) inhibition of ICG-AE105 tumor uptake by a bolus injection of the natural uPAR ligand pro-uPA, and finally 3) the histological colocalization of ICG-AE105 fluorescence and immunohistochemical detected human uPAR on resected tumor slides. Taken together, our data supports the potential use of this probe for intra-operative optical guidance in cancer surgery to ensure complete removal of tumors while preserving adjacent, healthy tissue.
Structure of the <i>Arabidopsis</i> Glucan Phosphatase LIKE SEX FOUR2 Reveals a Unique Mechanism for Starch Dephosphorylation (2013)

Starch is a water-insoluble, Glc-based biopolymer that is used for energy storage and is synthesized and degraded in a diurnal manner in plant leaves. Reversible phosphorylation is the only known natural starch modification and is required for starch degradation in planta. Critical to starch energy release is the activity of glucan phosphatases; however, the structural basis of dephosphorylation by glucan phosphatases is unknown. Here, we describe the structure of the Arabidopsis thaliana starch glucan phosphatase like sex four2 (LSF2) both with and without phospho-glucan product bound at 2.3Å and 1.65Å, respectively. LSF2 binds maltohexaose-phosphate using an aromatic channel within an extended phosphatase active site and positions maltohexaose in a C3-specific orientation, which we show is critical for the specific glucan phosphatase activity of LSF2 toward native Arabidopsis starch. However, unlike other starch binding enzymes, LSF2 does not possess a carbohydrate binding module domain. Instead we identify two additional glucan binding sites located within the core LSF2 phosphatase domain. This structure is the first of a glucan-bound glucan phosphatase and provides new insights into the molecular basis of this agriculturally and industrially relevant enzyme family as well as the unique mechanism of LSF2 catalysis, substrate specificity, and interaction with starch granules.
Design and Synthesis of Fungal-Selective Resorcylate Aminopyrazole Hsp90 Inhibitors (2019)

The molecular chaperone Hsp90, essential in all eukaryotes, plays a multifaceted role in promoting survival, virulence, and drug resistance across diverse pathogenic fungal species. The chaperone is also critically important, however, to the pathogen's human host, preventing the use of known clinical Hsp90 inhibitors in antifungal applications due to concomitant host toxicity issues. With the goal of developing Hsp90 inhibitors with acceptable therapeutic indices for the treatment of invasive fungal infections, we initiated a program to design and synthesize potent inhibitors with selective activity against fungal Hsp90 isoforms over their human counterparts. Building on our previously reported derivatization of resorcylate natural products to produce fungal-selective compounds, we have developed a series of synthetic aminopyrazole-substituted resorcylate amides with broad, potent, and fungal-selective Hsp90 inhibitory activity. Herein we describe the synthesis of this series, as well as biochemical structure-activity relationships driving selectivity for the Hsp90 isoforms expressed by <i>Cryptococcus neoformans</i> and <i>Candida albicans</i>, two pathogenic fungi of major clinical importance.
Pyridinium‐Based Cationic Lipids as Gene‐Transfer Agents (2003)

Abstract Cationic lipids are a promising alternative to viral vectors for gene therapy, allowing the delivery of larger plasmids without immunogenicity, despite their lower transfection efficiency. Among them, heterocyclic systems with imidazolium or pyridinium polar head groups have definite advantages such as the excellent transfection profiles and low cytotoxicity. Our approach for synthesizing heterocyclic cationic lipids differs from those previously described because we synthesize a pyridinium ring from simple starting materials. First a pyrylium salt is formed via diacylation of alkenes. The pyrylium salt is then converted by primary amines into pyridinium salts. Appropriate choice of the primary amine allows the attachment of two hydrophobic chains yielding compounds 21A and 25A (with various chain lengths derived from palmitic, stearic and oleic acids). The same strategy allowed the preparation of lipophilic derivatives 21B , 25B useful as strongly fluorescent markers for the study of the properties of biological membranes. Preliminary tests with some of the compounds 21A and 25A , on several cell lines, showed comparable transfection efficiencies and lower cytotoxicity than those obtained with standard commercial transfection agents. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Data placement across the cache hierarchy: Minimizing data movement with reuse-aware placement (2016)

Modern processors employ multiple levels of caching to address bandwidth, latency and performance requirements. The behavior of these hierarchies is determined by their approach to data placement and data eviction. Recent research has developed many intelligent data eviction policies, but cache hierarchies remain primarily either exclusive or inclusive with regards to data placement. This means that today's cache hierarchies typically install accessed data into all cache levels at one point or another, regardless of whether the data is reused in each level. Such data movement wastes energy by installing data into cache levels where the data is not reused.
Genome-wide identification of WRKY45-regulated genes that mediate benzothiadiazole-induced defense responses in rice (2013)

These data suggest a role of WRKY45 in BTH-induced disease resistance as a master regulator of the transcriptional cascade regulating defense responses in one of two branches in the rice SA pathway.