gebhart/patrepeval huggingface dataset:
Multizelluläre Tumor Spheroide – Ein Modellsystem zur Untersuchung der CD95 Liganden-induzierten Apoptose von HBV-infizierten Hepatozyten (2011)

Multizelluläre Tumor Spheroide (MCTS) stellen ein gut etabliertes 3-D in vitro Modellsystem dar, welches die pathophysiologische in vivo Situation in Tumormikroregionen simuliert. Insbesondere ist es mithilfe von MCTS möglich Tumor-, Immunzell-Interaktionen zu analysieren. Eine akute Hepatitis-B-Virus (HBV)-Infektion ist durch eine starke, multispezifische CD8+ T-Zellantwort gekennzeichnet. Der genaue molekulare Mechanismus der T-Zell vermittelten Immunantwort ist noch nicht vollständig geklärt. Wir konnten bisher zeigen, dass ein intaktes CD95-Apoptose-System essentiell für die Elimination HBV-infizierter Hepatozyten ist. Ziel dieser Arbeit war es, die CD95-vermittelte Apoptose von HBV-infizierten Leberzellen durch CD95 Liganden-exprimierende Lymphozyten näher zu charakterisieren.
Zebrafish Bioassay-Guided Natural Product Discovery: Isolation of Angiogenesis Inhibitors from East African Medicinal Plants (2011)

Natural products represent a significant reservoir of unexplored chemical diversity for early-stage drug discovery. The identification of lead compounds of natural origin would benefit from therapeutically relevant bioassays capable of facilitating the isolation of bioactive molecules from multi-constituent extracts. Towards this end, we developed an in vivo bioassay-guided isolation approach for natural product discovery that combines bioactivity screening in zebrafish embryos with rapid fractionation by analytical thin-layer chromatography (TLC) and initial structural elucidation by high-resolution electrospray mass spectrometry (HRESIMS). Bioactivity screening of East African medicinal plant extracts using fli-1:EGFP transgenic zebrafish embryos identified Oxygonum sinuatum and Plectranthus barbatus as inhibiting vascular development. Zebrafish bioassay-guided fractionation identified the active components of these plants as emodin, an inhibitor of the protein kinase CK2, and coleon A lactone, a rare abietane diterpenoid with no previously described bioactivity. Both emodin and coleon A lactone inhibited mammalian endothelial cell proliferation, migration, and tube formation in vitro, as well as angiogenesis in the chick chorioallantoic membrane (CAM) assay. These results suggest that the combination of zebrafish bioassays with analytical chromatography methods is an effective strategy for the rapid identification of bioactive natural products.
TG101209, a Selective JAK2 Kinase Inhibitor, Suppresses Endogenous and Cytokine-Supported Colony Formation from Hematopoietic Progenitors Carrying JAK2V617F or MPLW515K/L Mutations. (2006)

Abstract Background: acquisition of somatic mutations including JAK2V617F or MPLW515L/K results in constitutive activation of JAK-STAT signaling that commonly characterizes myeloproliferative disorders (MPD). JAK2 is the central signaling mediator for most hematopoietic cytokines in this signaling pathway. Hypothesis: small molecule JAK2 inhibitors may have a therapeutic role in MPD regardless of JAK2 mutation status. Methods: We studied effects of the JAK2 inhibitor, TG101209, in a cell-free kinase assay, relevant cell lines, an in vivo phosphorylation assay, and primary cells from MPD patients carrying JAK2V617F or MPLW515L/K mutations. Results: in a cell-free kinase assay, TG101209 inhibited JAK2 potently (IC50=6nM) and displayed selectivity relative to JAK3, ABL, and VEGFR2 kinases (IC50=170nM, 820nM, and 150nM, respectively). In cell proliferation assays, TG101209 inhibited JAK2-expressing Ba/F3 cells (IC50=280nM) and JAK2V617F-homozygous human erythroleukemia (HEL) cells (IC50=300nM), but not BCR-ABL-carrying K562 cells (IC50&gt;2μM). At 24 hours, TG101209 (600nM) induced apoptosis of HEL cells but not K562 cells (40% and 5%, respectively). SCID mice injected intravenously with Ba/F3-JAK2V617F cells developed significant disease burden including massive splenomegaly due to tumor infiltration (day 12). We observed marked decrease in STAT5 phosphorylation in splenic tumors 5 hours after administration of 2 oral doses of TG101209 (50 mg/kg) in this in vivo model. Based on the above data, we plated patient-derived CD34+ cells in methylcellulose (0nM, 300nM, and 600nM TG101209) with and without cytokines. We studied 2 controls and 9 MPD patients: PV=5 (all JAK2V617F+) and AMM=4 (3 were MPLW515L/K+) for colony number, colony size, and colony mutation burden, under each assay condition. TG101209 inhibited overall colony growth from MPD patients (IC50=300–600nM), and it preferentially suppressed growth of mutant colonies relative to wild type in both of 2 MPLW515K+ patients (AMM1 and AMM2) and in 3 of 5 JAK2V617+ patients (PV1-PV3) (Table). Conclusions: TG101209 potently inhibits cell growth that is dependent on constitutive JAK-STAT signaling. Furthermore, for MPD patient-derived cells, TG101209 preferentially suppresses growth of progenitors carrying JAK-activating mutations (MPLW515K&gt;JAK2V617F&gt;MPLW515L). Hence, our data supports the strategy of targeting aberrant JAK-pathway signaling in MPD as a viable therapeutic approach. Patient Mutation IC50 (nM) No Drug (% colonies mutation-positive) TG101209 (% colonies mutation-positive) Erythroid Myeloid Erythroid Myeloid Erythroid Myeloid Normal WT 1000 600 n/a PV1 JAK2V617F ~600 300–600 82 90 36 70 PV2 JAK2V617F ~300 70 55 60 20 PV3 JAK2V617F NA 20 30 30 0 PV4 JAK2V617F &gt;600 ~600 7 10 17 10 PV5 JAK2V617F ~300 300–600 64 92 82 100 AMM1 MPLW515K &lt;300 ~300 100 90 0 20 AMM2 MPLW515K 300–600 ~300 100 90 25 36 AMM3 MPLW515L 300–600 300–600 100 100 92 90 AMM4 WT &gt;600 300–600 n/a
CTNI-36. SAFETY OF ONC201 ADMINISTERED TWO CONSECUTIVE DAYS PER WEEK IN PEDIATRIC H3 K27M-MUTANT GLIOMA PATIENTS (2021)

Abstract ONC201, an anti-cancer DRD2 antagonist and ClpP agonist, is in Phase II trials for adult H3 K27M-mutant diffuse midline gliomas. The recommended phase 2 dose (RP2D) of 625mg ONC201 once a week has been established as a biologically active dose that is well tolerated in adult and pediatric populations. Radiographic regressions with single agent ONC201 have been reported in recurrent H3 K27M-mutant glioma patients. In another study, twice/week dosing was explored in adult patients and deemed to be safe (no DLTs observed). This warranted exploration of twice/week dosing in pediatric patients and will be discussed in this presentation. This multi-arm, dose-escalation and dose-expansion trial (ONC014; NCT03416530) determined the pediatric RP2D of ONC201 administered once per week and twice per week on two consecutive days. ONC201 was orally administered and scaled by body weight. Dose escalation was performed by a 3 + 3 design beginning with two 125mg capsules less than the adult RP2D equivalent. Twelve children (8 females; 4 males) with H3 K27M-mutant gliomas (pons: 8; thalamus: 2; spinal cord: 2) aged 4-19 years have been treated post-radiation: 3 at dose level -1; 3 at dose level 1; 6 as part of the dose expansion cohort on dose level 2. Median KPS was 90 (range 70-100). One treatment cycle was 21 days (6 doses), which also defined the DLT window. Patients were on-treatment for a median length of 4 cycles (range: 2-11). Twice weekly dosing of ONC201 was tolerated well, as observed with weekly dosing, with no instance of DLT. A total of 4 SAEs were reported, none of which were related to the study drug. The most common AEs (regardless of relatedness) included headache, facial nerve disorder, abducens nerve disorder, nausea, fatigue and ataxia. Additional safety data, PK, and clinical outcomes from this arm will be reported.
Synthesis and Thermal Rearrangement of C,N-Dialkynyl Imines:  A Potential Aza-Bergman Route to 2,5-Didehydropyridine (1997)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTSynthesis and Thermal Rearrangement of C,N-Dialkynyl Imines: A Potential Aza-Bergman Route to 2,5-DidehydropyridineWendi M. David and Sean M. KerwinView Author Information Division of Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin Austin, Texas 78712 Cite this: J. Am. Chem. Soc. 1997, 119, 6, 1464–1465Publication Date (Web):February 12, 1997Publication History Received8 July 1996Published online12 February 1997Published inissue 1 February 1997https://pubs.acs.org/doi/10.1021/ja962328rhttps://doi.org/10.1021/ja962328rrapid-communicationACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views846Altmetric-Citations62LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Aromatic compounds,Chemical reactions,Hydrocarbons,Nitrogen compounds,Rearrangement Get e-Alerts
Intermolecular Interactions and In Vitro Performance of Methyl Anthranilate in Commercial Sunscreen Formulations (2021)

In order to afford the required level of broad-spectrum photoprotection against UV-B and UV-A radiation, sunscreens must contain a combination of UV filters. It is important that any interactions between UV filters do not adversely affect their photostability nor the overall photostability of the sunscreen formulation. In this work, we explore the feasibility of using methyl anthranilate (MA) as an alternative to the photo-unstable UV-A filter, avobenzone. From the in vitro studies presented here, we conclude that MA does not provide sufficient UV-A protection on its own but that it is more photostable in formulation than avobenzone. In addition, we found that both octocrylene (OCR) and ethylhexyl methoxycinnamate (EHMC), two commonly used UV-B filters, can stabilize MA through quenching of its triplet states, as previously reported, which has a demonstrable effect in formulation. In contrast with previously reported observations for mixtures of EHMC and avobenzone, we found no evidence of [2+2] photocycloadditions taking place between EHMC and MA. This work demonstrates how a clear insight into the photophysics and photochemistry of UV filters, as well as the interactions between them, can inform formulation design to predict sunscreen performance.
PV Module-Level CHB Inverter with Integrated Battery Energy Storage System (2019)

In this paper, a photovoltaic (PV) module-level Cascaded H-Bridge (CHB) inverter with an integrated Battery Energy Storage System (BESS) is proposed. The advantages and drawbacks of the CHB circuit architecture in distributed PV generation systems are highlighted. The main benefits are related to the higher granularity of the PV power control, which mitigates mismatch effects, thus increasing the power harvesting. Nevertheless, heavy unbalanced configurations due to the intermittent nature of PV sources need to be properly addressed. In order to smooth the PV fluctuations, a Battery Energy Storage System is used to provide both an energy buffer and coordination of power supply and demand to obtain a flat profile of the output power. In particular, by exploiting the inherent modularity of the conversion circuit, a distributed storage system is also implemented by splitting the battery into smaller units each of which represents the backup module of a single power cell of the PV CHB. The proposed design and control strategy allows overcoming the operating limits of PV CHB inverter. Simulation results, carried out on a single-phase nineteen-level PV CHB inverter, evidence the effectiveness of the proposed design and control approach to minimize the adverse impact of deep mismatch conditions, thus enabling continuous power output by compensating PV power fluctuations.
Developing Cardiac and Skeletal Muscle Share Fast-Skeletal Myosin Heavy Chain and Cardiac Troponin-I Expression (2012)

Skeletal muscle derived stem cells (MDSCs) transplanted into injured myocardium can differentiate into fast skeletal muscle specific myosin heavy chain (sk-fMHC) and cardiac specific troponin-I (cTn-I) positive cells sustaining recipient myocardial function. We have recently found that MDSCs differentiate into a cardiomyocyte phenotype within a three-dimensional gel bioreactor. It is generally accepted that terminally differentiated myocardium or skeletal muscle only express cTn-I or sk-fMHC, respectively. Studies have shown the presence of non-cardiac muscle proteins in the developing myocardium or cardiac proteins in pathological skeletal muscle. In the current study, we tested the hypothesis that normal developing myocardium and skeletal muscle transiently share both sk-fMHC and cTn-I proteins. Immunohistochemistry, western blot, and RT-PCR analyses were carried out in embryonic day 13 (ED13) and 20 (ED20), neonatal day 0 (ND0) and 4 (ND4), postnatal day 10 (PND10), and 8 week-old adult female Lewis rat ventricular myocardium and gastrocnemius muscle. Confocal laser microscopy revealed that sk-fMHC was expressed as a typical striated muscle pattern within ED13 ventricular myocardium, and the striated sk-fMHC expression was lost by ND4 and became negative in adult myocardium. cTn-I was not expressed as a typical striated muscle pattern throughout the myocardium until PND10. Western blot and RT-PCR analyses revealed that gene and protein expression patterns of cardiac and skeletal muscle transcription factors and sk-fMHC within ventricular myocardium and skeletal muscle were similar at ED20, and the expression patterns became cardiac or skeletal muscle specific during postnatal development. These findings provide new insight into cardiac muscle development and highlight previously unknown common developmental features of cardiac and skeletal muscle.
Online TCP trajectory planning for redundant continuum manipulators using quadratic programming (2016)

Continuum manipulators enable new fields of application by their inherent flexibility and continuous deformations. However, they cannot compete with conventional robots yet. This is partially caused by a lack of practical and powerful trajectory generation algorithms. Therefore, an online TCP trajectory generator for redundant continuum manipulators has been developed, that computes desired actuator states for given task variables that can be used for actuator controllers. Using the fast gradient optimization algorithm and quadratic programming, actuator velocities are optimized considering actuator constraints with respect to a cost function including the differential kinematics. Experiments prove the online capabilities of the proposed trajectory generation approach. Furthermore, the presented method can be used for controlling continuum robots by incorporating inputs from human-machine-interaction devices.
Antibacterial Polymers for Dental Adhesives and Composites (2017)

This chapter contains sections titled: Introduction Major Damage from Oral Biofilm Formed: The Acid Production The Chemistry of Current Dental Adhesives and Composites The Need for Treatments Targeting Oral Cariogenic Biofilms Classification of Antibacterial Polymers for Dental Materials Mechanisms of Action of Antibacterial Monomers Antibacterial Properties of Dental Adhesives and Composites Containing Antibacterial Monomers Considerations of Mechanical Properties Summary and Prospects Acknowledgments
ChemInform Abstract: Iridoids: The Structure Elucidation of Specionin Based on Chemical Evidence and 1H NMR Analysis. (1987)

Abstract The title compound (XIc) is an effective antifeedant against the Eastern spruce budworm.
The frequency spectrum of polar modulated PWM signals and the image problem (2010)

Pulse-width modulators (PWMs) are implemented in wireless transmitters to utilize highly efficient switched-mode power amplifiers (SMPAs) such as Class-D,E,F,J amplifiers. This paper gives the analytical expressions for the natural-sampling trailing-edge PWM (TE-NPWM) signals with input signals bounded by [0, 1]. Such PWM modulators can be incorporated in a polar architecture. Important relations of polar modulated PWM signals are analyzed in detail by exploiting the results of the analysis. The image problem is illustrated when a baseband PWM signal is modulated to the passband with the phase-modulated carrier. A properly designed lowpass filter can be used to reduce the image distortions, but increases the total design costs. It further introduces extra delay and has the possible drawback of reducing the overall efficiency. Based on the spectral analysis, two alternative approaches are proposed to show how the image distortions can be reduced without a lowpass filter. The performance of the presented approaches for the image reduction is demonstrated through numerical simulations.
Effect of Ion Concentration on the Electro-Optic Response in Polymer-Stabilized Cholesteric Liquid Crystals (2020)

We have previously reported that the application of a DC field can adjust the position and/or bandwidth of the selective reflection notch in polymer-stabilized cholesteric liquid crystals (PSCLCs). The proposed mechanism of these electro-optic (EO) response is ion-facilitated electromechanical deformation of the polymer stabilizing network. Accordingly, the concentration of ions trapped within the polymer network should considerably influence the EO response of PSCLC. Our prior studies have indicated that photoinitiators can increase ion density in PSCLC by an order of magnitude. Here, we isolate the contribution of ionic impurities associated with liquid crystal monomers (LCMs) by utilizing initiator-less polymerization. PSCLCs prepared with LCM with low ion concentration show bandwidth broadening of the reflection band whereas PSCLCs prepared with LCM with high ion concentration exhibit a red shifting tuning of the reflection band. The extent of the tuning or bandwidth broadening of the CLC reflection band depends on the concentration of LCMs and the chirality of the LCM.
Emerging translational science discoveries, clonal approaches, and treatment trends in chronic myeloproliferative neoplasms (2019)

The 60th American Society of Hematology (ASH) held in San Diego in December 2018 was followed by the 13th Post-ASH chronic myeloproliferative neoplasms (MPNs) workshop on December 4 and 5, 2018. This closed annual workshop, first introduced in 2006 by Goldman and Mughal, was organized in collaboration with Alpine Oncology Foundation and allowed experts in preclinical and clinical research in the chronic MPNs to discuss the current scenario, including relevant presentations at ASH, and address pivotal open questions that impact translational research and clinical management. This review is based on the presentations and deliberations at this workshop, and rather than provide a resume of the proceedings, we have selected some of the important translational science and treatment issues that require clarity. We discuss the experimental and observational evidence to support the intimate interaction between aging, inflammation, and clonal evolution of MPNs, the clinical impact of the unfolding mutational landscape on the emerging targets and treatment of MPNs, new methods to detect clonal heterogeneity, the challenges in managing childhood and adolescent MPN, and reflect on the treatment of systemic mastocytosis (SM) following the licensing of midostaurin.
Search for the Standard Model Higgs Boson in the Decay ChannelH→ZZ→4linppCollisions ats=7  TeV (2012)

A search for a Higgs boson in the four-lepton decay channel H→ZZ, with each Z boson decaying to an electron or muon pair, is reported. The search covers Higgs boson mass hypotheses in the range of 110<m(H)<600 GeV. The analysis uses data corresponding to an integrated luminosity of 4.7 fb(-1) recorded by the CMS detector in pp collisions at √s=7 TeV from the LHC. Seventy-two events are observed with four-lepton invariant mass m(4ℓ)>100 GeV (with 13 below 160 GeV), while 67.1±6.0 (9.5±1.3) events are expected from background. The four-lepton mass distribution is consistent with the expectation of standard model background production of ZZ pairs. Upper limits at 95% confidence level exclude the standard model Higgs boson in the ranges of 134-158 GeV, 180-305 GeV, and 340-465 GeV. Small excesses of events are observed around masses of 119, 126, and 320 GeV, making the observed limits weaker than expected in the absence of a signal.
Local Global Tradeoffs in Metric Embeddings (2007)

Suppose that every k points in a metric space X are D-distortion embeddable into <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">lscr</sub> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> . We give upper and lower bounds on the distortion required to embed the entire space X into <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">lscr</sub> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> . This is a natural mathematical question and is also motivated by the study of relaxations obtained by lift-and-project methods for graph partitioning problems. In this setting, we show that X can be embedded into <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">lscr</sub> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> with distortion O(D times log(|X|/k)). Moreover, we give a lower bound showing that this result is tight if D is bounded away from I. For D = 1 + delta we give a lower bound of Omega(log(|X|/k/ log( 1/delta)); and for D = 1, we give a lower bound of Omega( log |X|/(log k +log log | X|)). Our bounds significantly improve on the results of Arora, Jjovdsz, Newman, Rabani, Rabinovich and Vempala, who initiated a study of these questions.
Nano-imaging the Few-fs Coherent Dynamics of Graphene (2021)

We demonstrate coherent spatio-temporal nano-imaging of graphene and its plasmonic nano-structures in four-wave mixing through adiabatic plasmonic nanofocusing. We resolve nanoscale heterogeneity and ultrafast dephasing affected by weakly screened carrier-carrier scattering.
Design and Control a Linear Motor with Planar V-Shaped Segmented Magnet Arrangement (2021)

In this paper, design and control of an asymmetric V-shaped segmented magnet arrangement for a linear permanent magnet (PM) synchronous motor is investigated. A single forcer single track structure is used in the investigation. Magnet arrangement for the track of the PM linear motor (PMLM) is also compared with an un-skewed magnet pole motor and the benefits of the proposed asymmetric V-shaped track are presented. Control of the machine at no-load and on-load are completed. The designed unconventional linear motor is manufactured and the test results are compared with the simulations. It is seen that there is good agreement between FEA and experimental results of the PMLSM. The benefits and the potentials of the V-shaped segmented magnet arrangement is also presented in the paper.