gebhart/patrepeval huggingface dataset:
Evaluation of PRKACA as a Therapeutic Target for Fibrolamellar Carcinoma (2022)

Abstract Background &amp; Aims Fibrolamellar carcinoma (FLC) is a rare, difficult-to-treat liver cancer primarily affecting pediatric and adolescent patients, and for which precision medicine approaches have historically not been possible. The DNAJB1-PRKACA gene fusion was identified as a driver of FLC pathogenesis. We aimed to assess whether FLC tumors maintain dependency on this gene fusion and determine if PRKACA is a viable therapeutic target. Methods FLC patient-derived xenograft (PDX) shRNA cell lines were implanted subcutaneously into female NOD-SCID mice and tumors were allowed to develop prior to randomization to doxycycline (to induce knockdown) or control groups. Tumor development was assessed every 2 days. To assess the effect of treatment with novel selective PRKACA small molecule kinase inhibitors, BLU0588 and BLU2864, FLC PDX tumor cells were implanted subcutaneously into NOD-SCID mice and tumors allowed to develop. Mice were randomized to treatment (BLU0588 and BLU2864, orally, once daily) or control groups and tumor size determined as above. Results Knockdown of DNAJB1-PRKACA reversed a FLC-specific gene signature and reduced PDX tumor growth in mice compared to the control group. Furthermore, FLC PDX tumor growth was significantly reduced with BLU0588 and BLU2864 treatment versus control ( P = 0.003 and P = 0.0005, respectively). Conclusions We demonstrated, using an inducible knockdown and small molecule approaches, that FLC PDX tumors were dependent upon DNAJB1 - PRKACA fusion activity. In addition, this study serves as a proof-of-concept that PRKACA is a viable therapeutic target for FLC and warrants further investigation.
Improvement of Human Keratinocyte Migration by a Redox Active Bioelectric Dressing (2014)

Exogenous application of an electric field can direct cell migration and improve wound healing; however clinical application of the therapy remains elusive due to lack of a suitable device and hence, limitations in understanding the molecular mechanisms. Here we report on a novel FDA approved redox-active Ag/Zn bioelectric dressing (BED) which generates electric fields. To develop a mechanistic understanding of how the BED may potentially influence wound re-epithelialization, we direct emphasis on understanding the influence of BED on human keratinocyte cell migration. Mapping of the electrical field generated by BED led to the observation that BED increases keratinocyte migration by three mechanisms: (i) generating hydrogen peroxide, known to be a potent driver of redox signaling, (ii) phosphorylation of redox-sensitive IGF1R directly implicated in cell migration, and (iii) reduction of protein thiols and increase in integrinαv expression, both of which are known to be drivers of cell migration. BED also increased keratinocyte mitochondrial membrane potential consistent with its ability to fuel an energy demanding migration process. Electric fields generated by a Ag/Zn BED can cross-talk with keratinocytes via redox-dependent processes improving keratinocyte migration, a critical event in wound re-epithelialization.
Efficacy and safety of a fixed combination of insulin degludec/insulin aspart in children and adolescents with type 1 diabetes: A randomized trial (2018)

IDegAsp + IAsp was non-inferior to IDet + IAsp regarding HbA1c, had similar hypoglycemia rates and required fewer injections.
Construction and Evaluation of Plasmonic Refractive Index Sensor Based on Changing the Number of Resonators and Changing Their Dimensions (2022)

In this paper, a plasmonic refractive index sensor based on MIM waveguide (metal_insulation_metal) with two plasmonic waveguides and five rings and two teeth and four rectangular cavities is proposed and designed. The refractive index of the resonators as well as the resonant wavelengths will be investigated by the time difference finite difference method. To achieve an optical sensor with excellent quality and performance, we change the number and type of amplifiers and their dimensions. In each stage of the simulation, we will only change the refractive index of the middle ring located in the middle of the two waveguides, and the refractive index of the other amplifiers remains the same. This challenge will help to form a more appropriate structure for optical sensors. The sensor built in this simulation has a balanced and suitable function for integrated circuits and helps researchers to better understand the design of plasmonic structures. It also has important applications in medical research, health care, drug manufacturing, security monitoring and environmental protection, internal security of countries and the battlefield.
Auditory-based formant estimation in noise using a probabilistic framework (2008)

We recently introduced a computationally efficient framework for tracking formants which combines a biologically inspired preprocessing for enhancing formants in spectrograms with a probabilistic framework for estimating formant trajectories. In contrast to previously published approaches our tracking scheme relies on the joint distribution of formants rather than using independent tracking instances for each formant separately. Therewith more precise formant estimates could be obtained. In this paper we will briefly review our algorithm and extend it by using more sophisticated models of the formants underlying dynamics. Furthermore, we will dwell on the robustness of our method for speech degraded by various types of noise. A comprehensive evaluation on a large publicly available database containing hand-labeled formant trajectories shows significant performance improvements in both clean and noisy speech compared to state of the art approaches.
Detection of single W-centers in silicon (2021)

Controlling the quantum properties of individual fluorescent defects in silicon is a key challenge towards advanced quantum photonic devices prone to scalability. Research efforts have so far focused on extrinsic defects based on impurities incorporated inside the silicon lattice. Here we demonstrate the detection of single intrinsic defects in silicon, which are linked to a tri-interstitial complex called W-center, with a zero-phonon line at 1.218$μ$m. Investigating their single-photon emission properties reveals new information about this common radiation damage center, such as its dipolar orientation and its photophysics. We also identify its microscopic structure and show that although this defect does not feature electronic states in the bandgap, Coulomb interactions lead to excitonic radiative recombination below the silicon bandgap. These results could set the stage for numerous quantum perspectives based on intrinsic luminescent defects in silicon, such as quantum integrated photonics, quantum communications and quantum sensing.
Regulation of angiogenic growth factor expression by hypoxia, transition metals, and chelating agents (1995)

Recent work has indicated that oxygen-sensing mechanism(s) resembling those controlling erythropoietin production operate in many non-erythropoietin-producing cells. To pursue the implication that such a system might control other genes, we studied oxygen-regulated expression of mRNAs for vascular endothelial growth factor, platelet-derived growth factor (PDGF) A and B chains, placental growth factor (PLGF), and transforming growth factor in four different cell lines and compared the characteristics with those of erythropoietin regulation. Oxygen-regulated expression was demonstrated for each gene in at least one cell type. However, the response to hypoxia (1% oxygen) varied markedly, ranging from a 13-fold increase (PDGF-B in Hep G2 cells) to a 2-fold decrease (PLGF in the trophoblastic line BeWo). For each gene/cell combination, both the magnitude and direction of the response to hypoxia were mimicked by exposure to cobaltous ions or two different iron-chelating agents, desferrioxamine and hydroxypyridinones. These similarities with established characteristics of erythropoietin regulation indicate that a similar mechanism of oxygen sensing is operating on a variety of vascular growth factors, and they suggest that chelatable iron is closely involved in the mechanism.
Mass spectrometric fragmentation of the peptide chain and β-methyl lanthionine bridges of the polycyclic peptide nisin (1991)

The mass spectra of the antibiotic peptide nisin measured with plasma desorption mass spectrometry (PDMS) and liquid secondary ionization mass spectrometry (LSIMS) show similar fragmentation patterns. Neither PDMS nor LSIMS ionization result in reduction of the lanthionine or β-methyl lanthionine bridges of intact nisin. It is proposed that many of the intense fragment peaks observed in the nisin mass spectra result from cleavage of both the peptide chain and the β-methyl lanthionine bridges.
Gene expression profiling to predict platinum-sensitivity in ovarian cancer. (2004)

2248 Objective: Gene expression profiling by cDNA microarrray can be used to accurately predict response to combination chemotherapy. We hypothesize that the profile of primary ovarian cancer will outperform all currently used clinical parameters in predicting disease outcome and identify those patients most likely to benefit from consolidation treatment. Methods : Twelve fresh-frozen epithelial ovarian cancer specimens obtained at primary surgical debulking were studied. All were advanced-stage, high grade and papillary serous histology. Postoperatively, patients received platinum-based chemotherapy and clinical outcome data was prospectively entered into a database. Those women with clinically-evident disease progression during primary chemotherapy or recurrence 6 months were considered “platinum-sensitive”. Five normal controls from patients undergoing surgery for benign reasons were analyzed for comparison. 5-10 μg of total RNA was isolated from all 17 cases, and the quality was confirmed by the Aligent 2100 Bioanalyzer. Each sample was profiled for mRNA expression levels of > 22,000 unique genes using the Affymetrix HG U133A Gene Chip. Array data was imported into MATRIX 1.23.1 and Gene Spring to identify over- and underexpressed genes in each group. Additional cases are being studied and will be presented. Class prediction profiles for platinum-sensitivity and platinum-resistance will then be determined by dividing tumors into “training” and “test” sets and cross-validated by the leave-one-out method. Results: Five platinum-sensitive and seven platinum-resistant ovarian cancers were compared to five normal controls. 633 genes were up-regulated at least 2 fold in the platinum-resistant group compared to the two other groups, and 83 of these showed at least a >4 fold difference (i.e. endomucin-2 (11 fold), Calpain 3 (8 fold), IGF-1 (8 fold)). 652 genes were down-regulated at least 2 fold. Sample clustering correlated well within each subset. Conclusion: Our preliminary findings suggest that gene expression profiling has the potential to predict platinum-sensitivity in ovarian cancer. This strategy has the potential to identify those patients most likely to benefit from novel or consolidation therapy. It also allows identification of possible targets to direct future novel therapy.
Abstract 2019: Tumor-targeting and efficacy of B7H3/GD2 bispecific SNIPER antibodies (2022)

Abstract Introduction: GD2 is expressed on neuroblastoma, melanomas, small cell lung cancers and sarcomas. While it is expressed minimally on normal tissues, it is expressed on nerve cells and, anti-GD2 (dinutuximab) treatment can cause neuropathic pain. To increase tumor specificity, we developed a bispecific SNIPER antibody to simultaneously target two tumor antigens (GD2 and B7H3). B7H3 is overexpressed on multiple tumor types, with minimal expression on most normal cells and is absent on nerve cells. The goal of this SNIPER is to enhance tumor-specificity, while reducing toxicity, ultimately improving efficacy for cancers expressing both targets. Experimental Procedures: SNIPER specificity was tested by flow cytometry for binding to GD2 +/- B7H3 expressing cells. Using an Incucyte S3, we tested antibody internalization properties [compared to anti-B7H3 and dinutuximab monoclonal antibodies (mAbs)] and antibody dependent cellular-cytotoxicity (ADCC) capabilities. Mice bearing variants of GD2/B7H3-expressing tumors were intravenously injected with 89Zr- radiolabeled SNIPER and its longitudinal in vivo biodistribution was monitored via positron emission tomography imaging. In vivo efficacy studies of SNIPER were tested against mice bearing either melanoma or neuroblastoma tumors that express both GD2 and B7H3. Summary of Data: In vitro and in vivo tumor specificity testing confirmed that SNIPER specifically targets B7H3+/GD2+ cells, but it does not bind to GD2+/B7H3- cells (which simulate nerve cells). We observed high internalization of anti-GD2 mAbs; we did not observe antibody internalization of either the SNIPER or anti-B7H3 mAbs. SNIPER was as effective at ADCC as the dinutuximab, but we saw minimal ADCC with the anti-B7H3 mAbs. An afucosylated version of SNIPER showed significantly enhanced ADCC compared to dinutuximab. Our in vivo efficacy studies found that SNIPER was as as dinutuximab when given at the same dose. Conclusions: The Fab arms of SNIPER targeting GD2 and B7H3 each have low-to-moderate affinity. SNIPER binds with strong avidity when both arms bind to their antigens on the same cell. Stronger avidity through both arms binding results in high-tumor specificity. Because SNIPER should not bind to nerves, it may be possible to administer increased doses of SNIPER beyond the tolerable dose of dinutuximab, which could further improve efficacy. Ongoing studies include antitumor efficacy testing, nerve binding assays and assessing reduction of pain in vivo with SNIPER. Citation Format: Amy K. Erbe, Arika Feils, Zack Rosenkrans, Jessica Wiwczar, Daniel Gerhardt, Bonnie Hammer, Mildred Felder, Mark Bercher, Alina Hampton, Lizzie Frankel, Dan Spiegelman, Noah Tsarovsky, Alexander Rakhmilevich, Jacquelyn Hank, Bryan Glaser, Reinier Hernandez, Roland Green, Paul M. Sondel. Tumor-targeting and efficacy of B7H3/GD2 bispecific SNIPER antibodies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2019.
Universal Mutual Information Privacy Guarantees for Smart Meters (2019)

Smart meters enable improvements in electricity distribution system efficiency at some cost in customer privacy. Users with home batteries can mitigate this privacy loss by applying charging policies that mask their underlying energy use. A battery charging policy is proposed and shown to provide universal privacy guarantees subject to a constraint on energy cost. The guarantee bounds our strategy's maximal information leakage from the user to the utility provider under general stochastic models of user energy consumption. The policy construction adapts coding strategies for non-probabilistic permuting channels to this privacy problem.
Vanadium(II) Heptacyanomolybdate(III)-Based Magnet Exhibiting a High Curie Temperature of 110 K (2010)

We prepared a vanadium heptacyanomolybdate-based magnet, V(II)(2)[Mo(III)(CN)(7)].(pyrimidine)(2).4.5H(2)O (VMo), with a Curie temperature (T(C)) of 110 K, which is the highest T(C) value in [Mo(III)(CN)(7)]-based magnets. Additionally, Mn(II)(2)[Mo(III)(CN)(7)].(pyrimidine)(2).2H(2)O (MnMo) of a monoclinic structure (P2(1)/n) with T(C) = 47 K was prepared to confirm the crystal structure of VMo.
Inhibition of Akt/mTOR pathway overcomes intrinsic resistance to dasatinib in triple-negative breast cancer (2020)

Currently, the only therapeutic choice for the treatment of triple-negative breast cancer (TNBC) is chemotherapy. In TNBC, despite strong preclinical data, clinical trials of molecular targeted drugs, such as the Src tyrosine kinase inhibitor dasatinib, have failed because of the heterogeneity of TNBC cells. Here, we examined the mechanism of intrinsic resistance to dasatinib in five TNBC cell lines. First, we divided the TNBC cell lines into those sensitive or resistant to dasatinib and found that activation of Src was inhibited in all of the cell lines. In contrast, we found that dasatinib inhibited Akt phosphorylation in only the dasatinib-sensitive cell lines. Consequently, we found that combination treatment with dasatinib and an inhibitor of Akt or mTOR suppressed cell proliferation more than did either monotherapy in the dasatinib-resistant cell lines. Finally, to mimic intrinsic resistance, we established a dasatinib-tolerant TNBC cell line. In this cell line, the combinational effect of Akt/mTOR inhibition with dasatinib was observed, as it was in the cell lines with intrinsic resistance. Together, the present results show that the effect of dasatinib in TNBC is independent of Src inhibition, and that Akt/mTOR inhibition might be an effective strategy to overcome TNBC cells with intrinsic dasatinib resistance.
SPR imaging for label-free multiplexed analyses of DNA N-glycosylase interactions with damaged DNA duplexes (2008)

Base excision repair (BER) is the major mechanism for the correction of damaged nucleobases resulting from the alkylation and oxidation of DNA. The first step in the BER pathway consists of excision of the abnormal base by several specific DNA N-glycosylases. A decrease in BER activity was found to be related to an increased risk of carcinogenesis and aging. To investigate BER activities we set up a new device for DNA repair analysis based on surface plasmon resonance imaging (SPRi). Oligonucleotides bearing an abnormal nucleoside, namely 8-oxo-7,8-dihydro-2'-deoxyguanosine and (5'S)-5',8-cyclopurine-2'-deoxynucleoside, were grafted by a pyrrole electro-copolymerization process on a glass prism coated with a gold layer. The latter label-free DNA sensor chip permits the detection of N-glycosylase/AP-lyase activity as well as the binding of repair proteins to DNA damage without cleavage activity. Thus, the Fapy DNA N-glycosylase (Fpg) protein is shown as expected to bind and then cleave its natural substrate, namely 8-oxo-7,8-dihydro-guanine, together with the resulting abasic site. Using the current SPR imaging-based DNA array we observed an original binding activity of Fpg towards the (5'S)-5',8-cyclodAdenosine residue. These results altogether show that SPR imaging may be used to simultaneously and specifically detect recognition and excision of several damaged DNA nucleobases, and constitutes an interesting technique to screen inhibitors of DNA repair proteins.
Deuterium nuclear magnetic resonance study of the stereochemistry of reduction of some organomercurials (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDeuterium nuclear magnetic resonance study of the stereochemistry of reduction of some organomercurialsWilliam Kitching, Annette R. Atkins, Geoffrey Wickham, and Vince AlbertsCite this: J. Org. Chem. 1981, 46, 3, 563–570Publication Date (Print):January 1, 1981Publication History Published online1 May 2002Published inissue 1 January 1981https://pubs.acs.org/doi/10.1021/jo00316a016https://doi.org/10.1021/jo00316a016research-articleACS PublicationsRequest reuse permissionsArticle Views153Altmetric-Citations17LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Evaluation of Hydrazine Reduction by Cellulose Acetate Filters Using Infrared Tunable Diode Laser Spectroscopy (2002)

Cellulose acetate (CA) filters have been investigated to determine their hydrazine (N2H4) breakthrough characteristics using a system based on tunable diode laser absorption spectroscopy (TDIAS). The breakthrough mass loading sorption curves for hydrazine were dependent on both the flow rate and the concentration. In experiments using a 4.5 ppmv hydrazine standard, the amounts of hydrazine retained by the CA filter were 4.25 microg at a flow rate of 2.82 L/min and 65 microg at a flow rate of 0.28 L/min. These loadings are much greater than the 31.5 ng/cigarette of hydrazine reported in smoke for unfiltered cigarettes. Further, CA filters exposed to four and eight puffs of smoke actually made the filter more efficient in retaining hydrazine compared to CA filters that had not been exposed to smoke. Therefore, if hydrazine is present in smoke at the levels reported in unfiltered cigarettes, all of the hydrazine would be trapped by the CA filter, and would be unable to break through during smoking. A unique feature of this analytical method is that the instrument does not require calibration after molecular parameters have been determined, in this case from previously acquired quantitative hydrazine FT-IR reference spectra.
Filling the big hole in HCI research (2015)

column Share on Filling the big hole in HCI research Author: Alan F. Blackwell University of Cambridge Computer Laboratory University of Cambridge Computer LaboratoryView Profile Authors Info & Claims InteractionsVolume 22Issue 6November - December 2015 pp 37–41https://doi.org/10.1145/2830317Published:28 October 2015Publication History 10citation963DownloadsMetricsTotal Citations10Total Downloads963Last 12 Months159Last 6 weeks27 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access