gebhart/patrepeval huggingface dataset:
Thyroid hormone receptors bind to defined regions of the growth hormone and placental lactogen genes. (1986)

The intracellular receptor for thyroid hormone is a protein found in chromatin. Since thyroid hormone stimulates transcription of the growth hormone gene through an unknown mechanism, the hypothesis that the thyroid hormone-receptor complex interacts with defined regions of this gene has been investigated in a cell-free system. Nuclear extracts from human lymphoblastoid IM-9 cells containing thyroid hormone receptors were incubated with L-3,5,3'-tri[125I]iodothyronine and calf thymus DNA-cellulose. Restriction fragments of the human growth hormone gene were added to determine their ability to inhibit labeled receptor binding to DNA-cellulose. These fragments encompassed nucleotide sequences from about three kilobase pairs upstream to about four kilobase pairs downstream from the transcription initiation site. The thyroid hormone-receptor complex bound preferentially to the 5'-flanking sequences of the growth hormone gene in a region between nucleotide coordinates -290 and -129. The receptor also bound to an analogous promoter region in the human placental lactogen gene, which has 92% nucleotide sequence homology with the growth hormone gene. These binding regions appear to be distinct from those that are recognized by the receptor for glucocorticoids, which stimulate growth hormone gene expression synergistically with thyroid hormone. The presence of thyroid hormone was required for binding of its receptor to the growth hormone gene promoter, suggesting that thyroid hormone renders the receptor capable of recognizing specific gene regions.
Data from SOX11 Inhibitors Are Cytotoxic in Mantle Cell Lymphoma (2023)

&lt;div&gt;AbstractPurpose:&lt;p&gt;Mantle cell lymphoma (MCL) is a fatal subtype of non–Hodgkin lymphoma. SOX11 transcription factor is overexpressed in the majority of nodal MCL. We have previously reported that B cell–specific overexpression of SOX11 promotes MCL pathogenesis via critically increasing BCR signaling &lt;i&gt;in vivo&lt;/i&gt;. SOX11 is an attractive target for MCL therapy; however, no small-molecule inhibitor of SOX11 has been identified to date. Although transcription factors are generally considered undruggable, the ability of SOX11 to bind to the minor groove of DNA led us to hypothesize that there may exist cavities at the protein–DNA interface that are amenable to targeting by small molecules.&lt;/p&gt;Experimental Design:&lt;p&gt;Using a combination of &lt;i&gt;in silico&lt;/i&gt; predictions and experimental validations, we report here the discovery of three structurally related compounds (SOX11i) that bind SOX11, perturb its interaction with DNA, and effect SOX11-specific anti-MCL cytotoxicity.&lt;/p&gt;Results:&lt;p&gt;We find mechanistic validation of on-target activity of these SOX11i in the inhibition of BCR signaling and the transcriptional modulation of SOX11 target genes, specifically, in SOX11-expressing MCL cells. One of the three SOX11i exhibits relatively superior &lt;i&gt;in vitro&lt;/i&gt; activity and displays cytotoxic synergy with ibrutinib in SOX11-expressing MCL cells. Importantly, this SOX11i induces cytotoxicity specifically in SOX11-positive ibrutinib-resistant MCL patient samples and inhibits Bruton tyrosine kinase phosphorylation in a xenograft mouse model derived from one of these subjects.&lt;/p&gt;Conclusions:&lt;p&gt;Taken together, our results provide a foundation for therapeutically targeting SOX11 in MCL by a novel class of small molecules.&lt;/p&gt;&lt;/div&gt;
Large-cell calcifying Sertoli cell tumors of the testes in pediatrics (2012)

The detection of LCCSCTs may point to an underlying genetic multiple neoplasia syndrome such as PJS or CNC. Surgery is rarely indicated and aromatase inhibitors constitute an effective treatment for those cases that are associated with gynecomastia and/or advanced skeletal age.
A realistic deformable prostate phantom for multimodal imaging and needle‐insertion procedures (2012)

The phantom's characteristics compare favorably with in vitro and in vivo measurements found in the literature. The authors believe that this realistic phantom could be of use to researchers studying new needle-based prostate diagnosis and therapy techniques.
Wide-Field InfraRed Survey Telescope (WFIRST) slitless spectrometer: design, prototype, and results (2016)

The slitless spectrometer plays an important role in the WFIRST mission for the survey of emission-line galaxies. This will be an unprecedented very wide field, HST quality 3D survey of emission line galaxies1. The concept of the compound grism as a slitless spectrometer has been presented previously. The presentation briefly discusses the challenges and solutions of the optical design, and recent specification updates, as well as a brief comparison between the prototype and the latest design. However, the emphasis of this paper is the progress of the grism prototype: the fabrication and test of the complicated diffractive optical elements and powered prism, as well as grism assembly alignment and testing. Especially how to use different tools and methods, such as IR phase shift and wavelength shift interferometry, to complete the element and assembly tests. The paper also presents very encouraging results from recent element tests to assembly tests. Finally we briefly touch the path forward plan to test the spectral characteristic, such as spectral resolution and response.
Capillary Wicking in Hierarchically Textured Copper Nanowire Arrays (2018)

Capillary wicking through homogeneous porous media remains challenging to simultaneously optimize due to the unique transport phenomena that occur at different length scales. This challenge may be overcome by introducing hierarchical porous media, which combine tailored morphologies across multiple length scales to design for the individual transport mechanisms. Here, we fabricate hierarchical nanowire arrays consisting of vertically aligned copper nanowires (∼100 to 1000 nm length scale) decorated with dense copper oxide nanostructures (∼10 to 100 nm length scale) to create unique property sets that include a large specific surface area, high rates of fluid delivery, and the structural flexibility of vertical arrays. These hierarchical nanowire arrays possess enhanced capillary wicking ( K/ R<sub>eff</sub> = 0.004-0.023 μm) by utilizing hemispreading and are advantageous as evaporation surfaces. With the advent and acceleration of flexible electronics technologies, we measure the capillary properties of our freestanding hierarchical nanowire arrays installed on curved surfaces and observe comparable fluid delivery to flat arrays, showing the difference of 10-20%. The degree of effective inter-nanowire pore and porosity is shown to govern the capillary performance parameters, thereby this study provides the design strategy for capillary wicking materials with unique and tailored combinations of thermofluidic properties.
Production of TiB <sub>2</sub> –TiN Composites by Combustion Synthesis and Their Properties (1997)

The self‐propagating high‐temperature synthesis (SHS) process has been applied to formation of composites consisting of TiB 2 and TiN ceramics synthesized simultaneously. Ti, B, and BN powders were used as raw materials. The SHS reaction was initiated by a tungsten heating coil. XRD experiments confirmed that the reaction was complete, and that only TiB 2 and TiN phases were detected. Microstructural observations revealed that both TiN and TiB 2 crystal grains had small sizes of less than 1 μm in the composites with high TiN content. Inhibition of grain growth can be attributed to the pinning effect of TiN grains. Excellent corrosion resistance was obtained for HCl reagent.
Faecal levels of calprotectin in systemic sclerosis are stable over time and are higher compared to primary Sjögren’s syndrome and rheumatoid arthritis (2014)

FC is a promising non-invasive biomarker for GI disease in SSc. In view of stable levels over time, FC could be a useful marker when novel, more specific drugs targeting the GI tract in SSc will be introduced.
Ginsenoside composition of <i>Panax ginseng</i> flower extracts obtained using different high hydrostatic pressure extraction conditions (2019)

Hyun Soo Kim, Gyu Ri Kim, Donghyun Kim, Cheng-Yi Zhang, Eun-Soo Lee, Nok Hyun Park, Junseong Park, Chang Seok Lee, Moon Sam Shin. J Plant Biotechnol 2019;46:56-60. https://doi.org/10.5010/JPB.2019.46.1.056
Multiple Low-Reactivity Class B Penicillin-Binding Proteins Are Required for Cephalosporin Resistance in Enterococci (2020)

<i>Enterococcus faecalis</i> and <i>Enterococcus faecium</i> are commensals of the gastrointestinal tract of most terrestrial organisms, including humans, and are major causes of health care-associated infections. Such infections are difficult or impossible to treat, as the enterococcal strains responsible are often resistant to multiple antibiotics. One intrinsic resistance trait that is conserved among <i>E. faecalis</i> and <i>E. faecium</i> is cephalosporin resistance, and prior exposure to cephalosporins is one of the most well-known risk factors for acquisition of an enterococcal infection. Cephalosporins inhibit peptidoglycan biosynthesis by acylating the active-site serine of penicillin-binding proteins (PBPs) to prevent the PBPs from catalyzing cross-linking during peptidoglycan synthesis. For decades, a specific PBP (known as Pbp4 or Pbp5) that exhibits low reactivity toward cephalosporins has been thought to be the primary PBP required for cephalosporin resistance. We analyzed other PBPs and report that in both <i>E. faecalis</i> and <i>E. faecium</i>, a second PBP, PbpA(2b), is also required for resistance; notably, the cephalosporin ceftriaxone exhibits a lethal effect on the Δ<i>pbpA</i> mutant. Strikingly, PbpA(2b) exhibits low intrinsic reactivity with cephalosporins <i>in vivo</i> and <i>in vitro</i> Unlike the Δ<i>pbp5</i> mutant, the Δ<i>pbpA</i> mutant exhibits a variety of phenotypic defects in growth kinetics, cell wall integrity, and cellular morphology, indicating that PbpA(2b) and Pbp5(4) are not functionally redundant and that PbpA(2b) plays a more central role in peptidoglycan synthesis. Collectively, our results shift the current understanding of enterococcal cephalosporin resistance and suggest a model in which PbpA(2b) and Pbp5(4) cooperate to coordinately mediate peptidoglycan cross-linking in the presence of cephalosporins.
Interaction of Mycobacterium tuberculosis Virulence Factor RipA with Chaperone MoxR1 Is Required for Transport through the TAT Secretion System (2016)

The virulence mechanism of mycobacteria is very complex. Broadly, the virulence factors can be classified as secretion factors, cell surface components, enzymes involved in cellular metabolism, and transcriptional regulators. The mycobacteria have evolved several mechanisms to secrete its proteins. Here, we have identified one of the virulence proteins of Mycobacterium tuberculosis, RipA, possessing peptidoglycan hydrolase activities secreted by the TAT secretion pathway. We also identified MoxR1 as a protein-protein interaction partner of RipA and demonstrated chaperone activity of this protein. We show that MoxR1-mediated folding is critical for the secretion of RipA within the TAT system. Inhibition of this export system in M. tuberculosis will prevent localization of peptidoglycan hydrolase and result in sensitivity to existing β-lactam antibiotics, opening up new candidates for drug repurposing.
Mutual optical intensity propagation through non-ideal mirrors (2017)

The mutual optical intensity (MOI) model is extended to include the propagation of partially coherent radiation through non-ideal mirrors. The propagation of the MOI from the incident to the exit plane of the mirror is realised by local ray tracing. The effects of figure errors can be expressed as phase shifts obtained by either the phase projection approach or the direct path length method. Using the MOI model, the effects of figure errors are studied for diffraction-limited cases using elliptical cylinder mirrors. Figure errors with low spatial frequencies can vary the intensity distribution, redistribute the local coherence function and distort the wavefront, but have no effect on the global degree of coherence. The MOI model is benchmarked against HYBRID and the multi-electron Synchrotron Radiation Workshop (SRW) code. The results show that the MOI model gives accurate results under different coherence conditions of the beam. Other than intensity profiles, the MOI model can also provide the wavefront and the local coherence function at any location along the beamline. The capability of tuning the trade-off between accuracy and efficiency makes the MOI model an ideal tool for beamline design and optimization.
Attachment of Borrelia burgdorferi within Ixodes scapularis mediated by outer surface protein A (2020)

Borrelia burgdorferi outer surface protein (Osp) A has been used as a Lyme disease vaccine that blocks transmission: OspA antibodies of immune hosts enter ticks during blood feeding and destroy spirochetes before transmission to the host can occur. B. burgdorferi produce OspA in the gut of unfed Ixodes scapularis ticks, and many spirochetes repress OspA production during the feeding process. This preferential expression suggests that OspA may have an important function in the vector. Here we show that OspA mediates spirochete attachment to the tick gut by binding to an I. scapularis protein. The binding domains reside in the central region and COOH-terminus of OspA. OspA also binds to itself, suggesting that spirochete-spirochete interactions may further facilitate adherence in the gut. OspA-mediated attachment in the tick provides a possible mechanism for how stage-specific protein expression can contribute to pathogenesis during the B. burgdorferi natural cycle.
Regulation of CFTR Trafficking by Its R Domain (2008)

Phosphorylation of the R domain is required for cystic fibrosis transmembrane conductance regulator (CFTR) channel gating, and cAMP/protein kinase A (PKA) simulation can also elicit insertion of CFTR into the plasma membrane from intracellular compartments (Bertrand, C. A., and Frizzell, R. A. (2003) Am. J. Physiol. 285, C1-C18). We evaluated the structural basis of regulated CFTR trafficking by determining agonist-evoked increases in plasma membrane capacitance (Cm) of Xenopus oocytes expressing CFTR deletion mutants. Expression of CFTR as a split construct that omitted the R domain (Deltaamino acids 635-834) produced a channel with elevated basal current (Im) and no DeltaIm or trafficking response (DeltaCm) upon cAMP/PKA stimulation, indicating that the structure(s) required for regulated CFTR trafficking are contained within the R domain. Additional deletions showed that removal of amino acids 817-838, a 22-amino acid conserved helical region having a net charge of -9, termed NEG2 (Xie, J., Adams, L. M., Zhao, J., Gerken, T. A., Davis, P. B., and Ma, J. (2002) J. Biol. Chem. 277, 23019-23027), produced a channel with regulated gating that lacked the agonist-induced increase in CFTR trafficking. Injection of NEG2 peptides into oocytes expressing split DeltaNEG2 CFTR prior to stimulation restored the agonist-evoked DeltaCm, consistent with the concept that this sequence mediates the regulated trafficking event. In support of this idea, DeltaNEG2 CFTR escaped from the inhibition of wild type CFTR trafficking produced by overexpression of syntaxin 1A. These observations suggest that the NEG2 region at the C terminus of the R domain allows stabilization of CFTR in a regulated intracellular compartment from which it traffics to the plasma membrane in response to cAMP/PKA stimulation.
Measuring the Activity of Leucine-Rich Repeat Kinase 2: A Kinase Involved in Parkinson’s Disease (2011)

Mutations in the LRRK2 (Leucine-Rich Repeat Kinase 2) gene are the most common cause of autosomal dominant Parkinson's disease. LRRK2 has multiple functional domains including a kinase domain. The kinase activity of LRRK2 is implicated in the pathogenesis of Parkinson's disease. Developing an assay to understand the mechanisms of LRRK2 kinase activity is important for the development of pharmacologic and therapeutic applications. Here, we describe how to measure in vitro LRRK2 kinase activity and its inhibition.
Progress curve algorithm for calculating enzyme activities from kinetic assay spectrophotometric measurements (1977)

&lt;p&gt;Background and Objectives: A 36-year-old woman underwent CO \n &lt;sub&gt;2&lt;/sub&gt; laser resurfacing for periocular rhytides using protective stainless steel Cox II ocular shields. Immediately after the treatment, corneal lesions were seen in both eyes. The left eye subsequent developed corneal ulceration and scarring, a deformed iris, cataract, and lower eye lashes showing signs of acute burns. The right cornea had a small inferior mid-peripheral superficial lesion and concomitant lower mid-peripheral burned eye lashes. Our objective was to determine the most likely cause of these ocular complications. Study: We estimated temperature–time combinations that could induce corneal injury and cataract. Heat conduction effects from a heated cornea to the lens and from a heated ring of periocular skin to the cornea were computed. The temperature response of a shield following CO \n &lt;sub&gt;2&lt;/sub&gt; laser irradiation was determined. Results: We computed that cataract can develop when the corneal temperature reaches, for example, 80 °C for 14 seconds. A periocular ring of heated skin contributes little to the corneal temperature. After 7 pulses of consecutive CO \n &lt;sub&gt;2&lt;/sub&gt; laser bursts in 7.5 seconds, the total shield area already reached a homogeneous temperature of 63 °C. Conclusion: Despite uncertainties in procedural details and modeling of cataract temperatures, the eye injuries were caused beyond doubt by heating of tear-covered metal eye shields by at least 10 consecutive but unintentional laser impacts. Lasers Surg. Med. 50:980–986, 2018.&lt;/p&gt;
A flexible air separation process: 1. Design and steady‐state optimizations (2019)

Abstract The flexible operation of energy‐intensive processes, such as cryogenic air separation, has economic potential due to increasing fluctuations of the electricity markets. Multiproduct air separation processes with high ratios of liquid product are very promising for flexible operation due to storable products. We present a process design with an integrated liquefication cycle and liquid assist operation, that facilitates a high liquid product ratio and a flexible process operation. We use a mechanistic dynamic process model in steady‐state process optimizations covering the wide operational range of the proposed process. The optimization results show that the power demand can be varied in a range from 3.5 to 28 MW without violating operational constraints by changing the nitrogen and oxygen production rates. Thus, the proposed process is a promising air separation candidate for flexible operation with respect to fluctuating electricity markets.
Endogenous signals initiating inflammation in the injured nervous system (2008)

Glial cells are known to respond to a variety of neural injuries and play an important role in tissue damage and repair in the injured nervous system. This glial response, which is initially characterized by the expression of proinflammatory cytokines and chemokines and the attraction of microglial cells toward sites of injury, literally occurs within seconds to minutes of the injury. This suggests that signals that are endogenous to the nervous system are responsible for initiating neuroinflammation. In this review, we summarize the most recent advances made in the identification of these endogenous signals and describe the receptors and signaling pathways by which these ligands stimulate the production of cytokines and chemokines. Among these endogenous damage signals are ligands for toll-like receptors, including several heat shock proteins and extracellular matrix components, as well as self-derived RNA and DNA and associated proteins. Growing evidence also suggests that nucleotides released upon injury and acting through P2 receptors, such as ATP and UTP or their analogues, could serve as endogenous signals for the rapid response of glial cells.
Drug-eluting microarrays to identify effective chemotherapeutic combinations targeting patient-derived cancer stem cells (2015)

A new paradigm in oncology establishes a spectrum of tumorigenic potential across the heterogeneous phenotypes within a tumor. The cancer stem cell hypothesis postulates that a minute fraction of cells within a tumor, termed cancer stem cells (CSCs), have a tumor-initiating capacity that propels tumor growth. An application of this discovery is to target this critical cell population using chemotherapy; however, the process of isolating these cells is arduous, and the rarity of CSCs makes it difficult to test potential drug candidates in a robust fashion, particularly for individual patients. To address the challenge of screening drug libraries on patient-derived populations of rare cells, such as CSCs, we have developed a drug-eluting microarray, a miniaturized platform onto which a minimal quantity of cells can adhere and be exposed to unique treatment conditions. Hundreds of drug-loaded polymer islands acting as drug depots colocalized with adherent cells are surrounded by a nonfouling background, creating isolated culture environments on a solid substrate. Significant results can be obtained by testing <6% of the cells required for a typical 96-well plate. Reliability was demonstrated by an average coefficient of variation of 14% between all of the microarrays and 13% between identical conditions within a single microarray. Using the drug-eluting array, colorectal CSCs isolated from two patients exhibited unique responses to drug combinations when cultured on the drug-eluting microarray, highlighting the potential as a prognostic tool to identify personalized chemotherapeutic regimens targeting CSCs.
Qualitative and quantitative improvement of optical tomographic reconstructed images via spatial deconvolution: three-dimensional case (2004)

A straightforward spatial deconvolution operation is used to compensate for the information-blurring property of first-order perturbation algorithms for diffuse optical tomography (DOT) image reconstruction. Applying this operation to 3D DOT images significantly improves image quality.
Toward the Design of Phosphorescent Emitters of Cyclometalated Earth-Abundant Nickel(II) and Their Supramolecular Study (2020)

A series of cyclometalating tridentate N^C^N and tetradentate N^C^N^O ligand-containing complexes of earth-abundant nickel(II) has been designed and synthesized. Among them, the carbazolylnickel(II) complex demonstrates, for the first time, an orange color room-temperature luminescence. Such a complex is also found to exhibit intense luminescence with excited state lifetimes in the submicrosecond regime at 77 K, suggesting the triplet nature of the emissive state. Meanwhile, the self-assembly property of the tetradentate ligand-containing nickel(II) complex in solution has been investigated. Owing to its nearly perfect square planar geometry, as evidenced by X-ray crystal structure determination, it is found to exhibit self-assembly properties with the aid of π-π interactions and possibly weak Ni···Ni interactions, which have been supported by DFT calculations and NCI plot. Indeed, the ground-state aggregation behavior of this complex has been confirmed by concentration-dependent UV-vis absorption spectroscopy. Moreover, in the solution-induced aggregation studies, upon the addition of nonsolubilizing solvents, the emergence of low-energy absorption bands has been realized, and such a complex is found to demonstrate interesting self-assembly behaviors to offer well-defined and highly ordered supramolecular architectures.
Comparaison des performances radioélectriques d'antennes monopoles filaires optiquement transparentes (2012)

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