gebhart/patrepeval huggingface dataset:
FAST-FNA molecular diagnostic assay facilitates rapid diagnosis and ntrk biomarker testing of salivary gland tumors. (2022)

e18089 Background: Primary epithelial salivary gland tumors (SGTs)are classified into 31 tumor types. Diagnosing SGTs through fine needle aspiration (FNA) biopsies is challenging due to the overlapping cytomorphologic features between benign and malignant tumors. In this study, we developed an innovative, multiplexed cycling technology which allows for the rapid cellular analyses of single cells obtained from FNA which can facilitate the rapid molecular analyses and diagnosis of SGTs. Methods: Antibodies against 29 cell surface markers associated with 7 SGT subtypes were validated and chemically modified via custom linker–bio-orthogonal quencher probes (FAST). Single cell homogenates and a FNA sample set representing 7 SGT subtypes were profiled by FAST cyclic staining, imaging, and automated computational analysis. A prediction model was generated utilizing a training set of 151,926 single cells obtained from primary SGTs (N = 26) and validated on a separate cohort of SGTs (N = 30). Companion biomarker testing, such as NTRK, was also assessed with the FAST technology. Results: The customized FAST-FNA SGT molecular diagnostic and biomarker panel was validated on human cell lines and specificity confirmed by both flow cytometry and clinical immunohistochemical staining on primary SGTs. The FAST molecular diagnostic assay was able to distinguish between benign and malignant SGTs with an accuracy of 0.86 for single-cell suspension samples and 0.88 for FNA samples. Profiling of multiple markers as compared to a single tumor marker increased the diagnostic accuracy of the SGTs, 0.82 as compared to 0.65-0.74, respectively. The results of the assay were highly reproducible and independent of the cell number sampled. NTRK expression in SGTs was also assessed by the FAST assay within hours, highlighting the potential therapeutic application of this technology. Conclusions: High dimensional single-cell profiling and molecular diagnostic testing on FNA samples are feasible at relatively low cost and as a rapid test. Application of the novel multiplexed single cell technology improves the diagnostic accuracy of SGT biopsy and facilitates multiplex biomarker testing from FNA samples. The customizable and modular FAST-FNA approach has relevance to multiple pathologies and organ systems where cytologic samples are often scarce and/or indeterminate resulting in improved diagnostic workflows and timely therapeutic clinical decision making.
A Planar Catechin Analogue Having a More Negative Oxidation Potential than (+)-Catechin as an Electron Transfer Antioxidant against a Peroxyl Radical (2003)

The hydrogen transfer reaction of antioxidative polyphenol with reactive oxygen species has proved to be the main mechanism for radical scavenging. The planar catechin (P1H(2)), in which the catechol and chroman structure in (+)-catechin (1H(2)) are constrained to be planar, undergoes efficient hydrogen atom transfer toward galvinoxyol radical, showing an enhanced protective effect against the oxidative DNA damage induced by the Fenton reaction. The present studies were undertaken to further characterize the radical scavenging ability of P1H(2) in the reaction with cumylperoxyl radical, which is a model radical of lipid peroxyl radical for lipid peroxidation. The kinetics of hydrogen transfer from catechins to cumylperoxyl radical has been examined in propionitrile at low temperature with use of ESR, showing that the rate of hydrogen transfer from P1H(2) is significantly faster than that from 1H(2). The rate was also accelerated by the presence of Sc(OSO(2)CF(3))(3). Such an acceleration effect of metal ion indicates that the hydrogen transfer reaction proceeds via metal ion-promoted electron transfer from P1H(2) to oxyl radical followed by proton transfer rather than via a one-step hydrogen atom transfer. The electrochemical ease of P1H(2) for the one-electron oxidation investigated by second-harmonic alternating current voltammetry strongly supports the two step mechanism for hydrogen transfer, resulting in the enhanced radical scavenging ability.
Complexes of Trypanosoma cruzi Sterol 14α-Demethylase (CYP51) with Two Pyridine-based Drug Candidates for Chagas Disease (2013)

Chagas disease, caused by the eukaryotic (protozoan) parasite Trypanosoma cruzi, is an alarming emerging global health problem with no clinical drugs available to treat the chronic stage. Azole inhibitors of sterol 14α-demethylase (CYP51) were proven effective against Chagas, and antifungal drugs posaconazole and ravuconazole have entered clinical trials in Spain, Bolivia, and Argentina. Here we present the x-ray structures of T. cruzi CYP51 in complexes with two alternative drug candidates, pyridine derivatives (S)-(4-chlorophenyl)-1-(4-(4-(trifluoromethyl)phenyl)-piperazin-1-yl)-2-(pyridin-3-yl)ethanone (UDO; Protein Data Bank code 3ZG2) and N-[4-(trifluoromethyl)phenyl]-N-[1-[5-(trifluoromethyl)-2-pyridyl]-4-piperi-dyl]pyridin-3-amine (UDD; Protein Data Bank code 3ZG3). These compounds have been developed by the Drugs for Neglected Diseases initiative (DNDi) and are highly promising antichagasic agents in both cellular and in vivo experiments. The binding parameters and inhibitory effects on sterol 14α-demethylase activity in reconstituted enzyme reactions confirmed UDO and UDD as potent and selective T. cruzi CYP51 inhibitors. Comparative analysis of the pyridine- and azole-bound CYP51 structures uncovered the features that make UDO and UDD T. cruzi CYP51-specific. The structures suggest that although a precise fit between the shape of the inhibitor molecules and T. cruzi CYP51 active site topology underlies their high inhibitory potency, a longer coordination bond between the catalytic heme iron and the pyridine nitrogen implies a weaker influence of pyridines on the iron reduction potential, which may be the basis for the observed selectivity of these compounds toward the target enzyme versus other cytochrome P450s, including human drug-metabolizing P450s. These findings may pave the way for the development of novel CYP51-targeted drugs with optimized metabolic properties that are very much needed for the treatment of human infections caused by eukaryotic microbial pathogens.
Ink Design Enabling Slot‐Die Coated Perovskite Solar Cells with >22% Power Conversion Efficiency, Micro‐Modules, and 1 Year of Outdoor Performance Evaluation (2023)

Abstract The next technological step in the exploration of metal‐halide perovskite solar cells is the demonstration of larger‐area device prototypes under outdoor operating conditions. The authors here demonstrate that when slot‐die coating the halide perovskite layers on large areas, ribbing effects may occur but can be prevented by adjusting the precursor ink's rheological properties. For formamidinium lead triiodide (FAPbI 3 ) precursor inks based on 2‐methoxyethanol, the ink viscosity is adjusted by adding acetonitrile (ACN) as a co‐solvent leading to smooth FAPbI 3 thin‐films with high quality and layer homogeneity. For an optimized content of 46 vol% of the ACN co‐solvent, a certified steady‐state performance of 22.3% is achieved in p‐i‐n FAPbI 3 ‐perovskite solar cells. Scaling devices to larger areas by making laser series‐interconnected mini‐modules of 12.7 cm 2 , a power conversion efficiency of 17.1% is demonstrated. A full year of outdoor stability testing with continuous maximum power point tracking on encapsulated devices is performed and it is demonstrated that these devices maintain close to 100% of their initial performance during winter and spring followed by a significant performance decline during warmer summer months. This work highlights the importance of the real‐condition evaluation of larger area device prototypes to validate the technological potential of halide perovskite photovoltaics.
Towards General and Efficient Active Learning (2021)

Active learning selects the most informative samples to exploit limited annotation budgets. Existing work follows a cumbersome pipeline that repeats the time-consuming model training and batch data selection multiple times. In this paper, we challenge this status quo by proposing a novel general and efficient active learning (GEAL) method following our designed new pipeline. Utilizing a publicly available pretrained model, our method selects data from different datasets with a single-pass inference of the same model without extra training or supervision. To capture subtle local information, we propose knowledge clusters extracted from intermediate features. Free from the troublesome batch selection strategy, all data samples are selected in one-shot through a distance-based sampling in the fine-grained knowledge cluster level. This whole process is faster than prior arts by hundreds of times. Extensive experiments verify the effectiveness of our method on object detection, image classification, and semantic segmentation. Our code is publicly available in https://github.com/yichen928/GEAL_active_learning.
Impact of dislocation density on performance and reliability of 1.3 μm InAs quantum dot lasers epitaxially grown on silicon (2021)

This paper reports on the impact of the quality of the epitaxial structure of InAs Quantum Dot (QD) lasers grown on silicon substrates on lifetime. To this aim, a series of current step-stress and constant-current aging experiments were carried out on two sets of Fabry-Pérot QD lasers, emitting at 1.3 μm and featuring two different Threading Dislocations Densities (TDDs) within the epilayers, nominally 6E7 cm<sup>-2</sup> (high TDD) grown on Si substrates and 500 cm<sup>-2 </sup>(low TDD) grown on lattice matched GaAs substrates. The results of the step-stress procedure indicate that i) the high-current optical performance of the lasers is limited by TDD, which reduces the bias range for useful Ground State (GS)-only operation and lowers the roll-off point of the optical output characteristic; ii) TDD contributes to the acceleration of the dominant optical degradation mechanism at high stress current levels, represented for this family of devices by the recombinationenhanced generation of defects in device regions close to the active layers; iii) dislocation density also accelerates optical degradation in GS regime. This process is primarily driven by the diffusion of Non-Radiative Recombination Centers (NRRCs) toward the active region of the devices, as demonstrated by the dependence of threshold current variation on the square root of time. These experimental results show that the presence of TDDs is the main limiting factor for the reliability of QD lasers for epitaxially-integrated silicon photonics applications, further confirming the outcome of previous statistical lifetime analyses carried out on devices featuring similar epitaxial structures.
MEASUREMENTS OF VELOCITY-ACCELERATION STATISTICS IN TURBULENT BOUNDARY LAYERS (2005)

An advanced laser Doppler velocimetry system is developed to acquire measurements of fluctuating velocity-acceleration statistics in turbulent boundary layers. The measurements give important insight into the near-wall turbulence structure since the statistical correlations of interest, uiaj appear directly in the Reynolds stress transport equations as a sum of the velocity-pressure gradient correlation, 1/ρ(ui(dp/dxj)+uj(dp/dxi)), the dissipation rate, 2ν(dui/dzk)(duj/dzk) and the viscous diffusion, ν∇2uiuj. The immediate power of such measurements is that combinations of terms in the Reynolds stress transport equation may be characterized by a single statistical measurement at one location in the flow−no gradients need be computed. In the present paper, data are presented for a constant-pressure 2D turbulent boundary layer at Reθ = 6800. Near-wall results for the dominant term in the velocity-acceleration tensor, the streamwise correlation uax, compare favorably with DNS for the same quantity at Reθ = 1410 and Reτ = 640; furthermore, the quantity exhibits no Reynolds number effects within experimental uncertainties. This study exhibits the potential of the technique to be applied to more complex flows, particularly those 3D separating flows in which the motions contributing to the velocity-acceleration correlations become dominant.
Occurrence of Mitochondria-targeted Late Embryogenesis Abundant (LEA) Gene in Animals Increases Organelle Resistance to Water Stress (2009)

Anhydrobiotic animals survive virtually complete loss of cellular water. The mechanisms that explain this phenomenon are not fully understood but often include the accumulation of low molecular weight solutes such as trehalose and macromolecules like Late Embryogenesis Abundant (LEA) proteins. Here we report for the first time the occurrence of a mitochondria-targeted LEA gene (Afrlea3m) product in an animal species. The deduced molecular mass of the 307-amino acid polypeptide from the brine shrimp Artemia franciscana is 34 kDa. Bioinformatic analyses reveal features typical of a Group 3 LEA protein, and subcellular localization programs predict targeting of the mature peptide to the mitochondrial matrix, based on an N-terminal, amphipathic presequence. Real-time quantitative PCR shows that Afralea3m mRNA is expressed manyfold higher in desiccation-tolerant embryonic stages when compared with intolerant nauplius larvae. Mitochondrial localization of the protein was confirmed by transfection of human hepatoma cells (HepG2/C3A) with a nucleotide construct encoding the first 70 N-terminal amino acids of AfrLEA3m in-frame with the nucleotide sequence for green fluorescence protein. The chimeric protein was readily incorporated into mitochondria of these cells. Successful targeting of a protein to human mitochondria by use of an arthropod signaling sequence clearly reveals the highly conserved nature of such presequences, as well as of the import machinery. Finally, mitochondria isolated from A. franciscana embryos, which naturally contain AfrLEA3m and trehalose, exhibit resistance to water stress (freezing) as evidenced by an unchanged capacity for oxidative phosphorylation on succinate + rotenone, a resistance that is absent in mammalian mitochondria lacking AfrLEA3m.
Abstract 12826: Importance of Flexibility in Shock Polarity With Subcutaneous Only Implantable Cardioverter-Defibrillators (2010)

Introduction: An entirely subcutaneous ICD (S-ICD) has recently been shown to be effective in treating patients with ventricular tachyarrhythmias. This study explored the clinical utility of incorp...
Equivalent Uniform Dose (Eud) Is a Predictor of Acute Rectal Toxicity in Patients with Prostate Cancer Treated with Intensity Modulated Radiotherapy (2003)

Khuntia, Deepak MD; Djemil, Toufik PhD; Levin-Plotnik, Daphne PhD; Hamilton, Russell J. PhD; Reuther, Alwyn M. MPH; Kupelian, Patrick A. MD Author Information
Suppression of mast-cell-mediated allergic inflammation byLindera obtusiloba (2011)

Allergic disease is a consequence of exposure to normally innocuous substances that elicit the activation of mast cells. Mast-cell-mediated allergic response is involved in many diseases such as anaphylaxis, allergic rhinitis, asthma and atopic dermatitis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. In this study, we investigated the effect of Lindera obtusiloba water extract (LOWE) on the mast-cell-mediated allergic inflammation and possible mechanism of action using in vitro and in vivo models. LOWE reduced histamine release from various types of mast cells activated by immunoglobulin E (IgE) or phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI). The inhibitory effect of LOWE on histamine release was mediated by calcium signal. LOWE decreased the PMACI-stimulated gene expression of proinflammatory cytokines such as tumor necrosis factor-α and interleukin-6 in human mast cells. The inhibitory effect of LOWE on the proinflammatory cytokines was nuclear factor (NF)-κB dependent. In addition, LOWE suppressed compound 48/80-induced systemic allergic reaction and serum histamine release in mice and IgE-mediated local allergic reactions. Our results indicate that LOWE inhibits mast-cell-derived allergic inflammation and involvement of calcium, histamine, proinflammatory cytokines and NF-κB in these effects.
Molecular characterization of a patient with central nervous system dysmyelination and cryptic unbalanced translocation between chromosomes 4q and 18q (2003)

We report on a 12-year-old boy who presented with delayed development and CNS dysmyelination. Genetic studies showed a normal 46,XY karyotype by routine cytogenetic analysis, and 46,XY.ish del(18)(q23)(D18Z1+, MBP-) by FISH using a locus-specific probe for the MBP gene (18q23). Though the patient appeared to have normal chromosome 18s by repeated high resolution banding analysis, his clinical features were suggestive of a deletion of 18q. These included hearing loss secondary to stenosis of the external auditory canals, abnormal facial features, and foot deformities. FISH studies with genomic probes from 18q22.3 to 18qter confirmed a cryptic deletion which encompassed the MBP gene. In an attempt to further characterize the deletion, whole genome screening was conducted using array based comparative genomic hybridization (array CGH) analysis. The array CGH data not only confirmed a cryptic deletion in the 18q22.3 to 18qter region of approximately 7 Mb, it also showed a previously undetected 3.7 Mb gain of 4q material. FISH studies demonstrated that the gained 4q material was translocated distal to the 18qter deletion breakpoint. The 18q deletion contains, in addition to MBP, other known genes including CYB5, ZNF236, GALR1, and NFATC1, while the gained 4q material includes the genes FACL1 and 2, KLKB1, F11 and MTNR1A. The use of these combined methodologies has resulted in the first reported case in which array CGH has been used to characterize a congenital chromosomal abnormality, highlighting the need for innovative molecular cytogenetic techniques in the diagnosis of patients with idiopathic neurological abnormalities.
A new method to graft titania using Grignard reagents (2013)

A new method to graft titania with organic groups has been developed. In contrast to common condensation based grafting methods, this method uses organometallic chemistry to bond organic groups directly at the surface. Thereby the introduction of hetero elements at the bonding interface is avoided.
New die bonding material with PSQ as a main agent having high heat dissipation (2022)

We have developed a new die bonding material by using our originally developed polysilsesquioxane(PSQ). By using this PSQ as the main agent and adding alumina filler, both high die shear strength and heat dissipation are achieved.
Development of a Field Emission Electron Microscope (1979)

A field emission electron microscope with highly stabilized gun and illuminating system was developed. Several experiments were made to demonstrate the high performance of the microscope. The brightness of the beam was more than that of the conventional ones, which feature was demonstrated by taking 300 Fresnel fringes and 3,000 bi-prism fringes. Furthermore, monochromatic feature of the microscope makes the effect of chromatic aberration smaller and the half-spacing fringes of nickel {220} planes (1/2 d220=62Å) were observed.
Synthesis and biological properties of 3‐methyl‐10‐propargyl‐5,8‐dideazafolic acid (1989)

Abstract The synthesis of N 3 ‐methyl‐10‐propargyl‐5,8‐dideazafolic acid ( 1b ) is described. Ring closure of methyl‐5‐methylanthranilate with chloroformamidine hydrochloride gave a high yield of pure 2‐amino‐4‐hydroxy‐6‐methylquinazoline treatment of which with iodomethane/sodium hydroxide provided the corresponding 3‐methylquinazoline (6) which was converted to its 2‐pivaloylamino derivative. This synthetic approach, next involving functionalisation of the 6‐methyl group, was not further pursued because of difficulty encountered in removing the pivaloyl group. Methyl 5‐methylanthranilate was treated with p ‐toluenesulfonyl chloride and the product then N ‐methylated. The tosyl group was cleaved with hydrogen bromide/phenol and the resulting methylamine ring‐closed with chloroformamidine hydrochloride to provide 2‐amino‐1,4‐dihydro‐1,6‐dimethyl‐4‐oxoquinazoline ( 11 ). The 2‐pivaloylamino derivative of 11 was prone to hydrolytic deamination when attempts were made to remove the pivaloyl group and further elaboration of this heterocycle, with the intention of obtaining N 1 ‐methyl‐10‐propargyl‐5,8‐dideazafolic acid was, too, not attempted. Di‐ t ‐butyl N ‐(4‐propargylamino)benzoyl)‐L‐glutamate was therefore prepared and coupled with 2‐amino‐6‐bromomethyl‐4‐hydroxyquinazoline hydrobromide. The resulting antifolate diester was N ‐monomethylated. Removal of the t ‐butyl groups with trifluoracetic acid afforded the target compound 1b and its structure was proved by degradation to the quinazoline 6 . Its IC 50 for L1210 thymidylate synthase (TS) was 26 μ M ; the control value for 10‐propargyl‐5,8‐dideazafolic acid ( 1a ) was 0.02 μM. Thus the substitution of the lactam hydrogen in 1a by a methyl group reduced the TS inhibition by 1300‐fold. Compound 1b was poorly cytotoxic to L1210 cells in culture (ID 50 &gt; 100 μM). An unperturbed lactam group in this class of antifolate is important for binding to TS.
The structure of gas-phase bradykinin fragment 1–5 (RPPGF) ions: An ion mobility spectrometry and H/D exchange ion-molecule reaction chemistry study (2005)

Ion mobility-mass spectrometry (IM-MS) data is interpreted as evidence that gas-phase bradykinin fragment 1-5 (BK1-5, RPPGF) [M + H](+) ions exist as three distinct structural forms, and the relative abundances of the structural forms depend on the solvent used to prepare the matrix-assisted laser desorption ionization (MALDI) samples. Samples prepared from organic rich solvents (90% methanol/10% water) yield ions having an ion mobility arrival-time distribution (ATD) that is dominated by a single peak; conversely, samples prepared using mostly aqueous solvents (10% methanol/90% water) yield an ATD composed of three distinct peaks. The BK1-5 [M + H](+) ions were also studied by gas-phase hydrogen/deuterium (H/D) exchange ion-molecule reactions and this data supports our interpretation of the IM-MS data. Plausible structures for BK1-5 ions were generated by molecular dynamics (MD). Candidate MD-generated structures correlated to measured cross-sections suggest a compact conformer containing a beta-turn whereas a more extended, open form does not contain such an interaction. This study illustrates the importance of intra-molecular interactions in the stabilization of the gas-phase ions, and these results clearly illustrate that solution-phase parameters (i.e., MALDI sample preparation) greatly influence the structures of gas-phase ions.
Reputation dynamics and convergence: A basis for evaluating reputation systems (2009)

Reputation is a crucial concept in dynamic multiagent environments and not surprisingly has received considerable attention from researchers.However, despite the large body of related work on reputation systems, no metrics exist to directly and quantitatively evaluate and compare them.We present a common conceptual interface for reputation systems and a set of four measurable desiderata that are broadly applicable across multiple domains.These desiderata employ concepts from dynamic systems theory to measure how a reputation system reacts to a strategic agent attempting to maximize its own utility.We study a diverse set of well-known reputation models from the literature in a moral hazard setting and identify a rich variety of characteristics that they support.We discuss the implications, strengths, and limitations of our desiderata.