gebhart/patrepeval huggingface dataset:
Hyper-Progressive Disease: The Potential Role and Consequences of T-Regulatory Cells Foiling Anti-PD-1 Cancer Immunotherapy (2020)

Antibody-mediated disruption of the programmed cell death protein 1 (PD-1) pathway has brought much success to the fight against cancer. Nevertheless, a significant proportion of patients respond poorly to anti-PD-1 treatment. Cases of accelerated and more aggressive forms of cancer following therapy have also been reported. Termed hyper-progressive disease (HPD), this phenomenon often results in fatality, thus requires urgent attention. Among possible causes of HPD, regulatory T-cells (Tregs) are of suspect due to their high expression of PD-1, which modulates Treg activity. Tregs are a subset of CD4<sup>+</sup> T-cells that play a non-redundant role in the prevention of autoimmunity and is functionally dependent on the X chromosome-linked transcription factor FoxP3. In cancer, CD4<sup>+</sup>FoxP3<sup>+</sup> Tregs migrate to tumors to suppress anti-tumor immune responses, allowing cancer cells to persist. Hence, Treg accumulation in tumors is associated with poor prognosis. In mice, the anti-tumor efficacy of anti-PD-1 can be enhanced by depleting Tregs. This suggests Tregs pose resistance to anti-PD-1 therapy. In this article, we review the relevant Treg functions that suppress tumor immunity and the potential effects anti-PD-1 could have on Tregs which are counter-productive to the treatment of cancer, occasionally causing HPD.
Identification of Recurrent Activating <i>HER2</i> Mutations in Primary Canine Pulmonary Adenocarcinoma (2019)

This study creates a foundation for molecular understanding of and drug development for canine lung cancer. These data also establish molecular contexts for comparative studies in dogs and humans of low mutation burden, never-smoker lung cancer, and mutant HER2 function and inhibition.
Protein kinase C (1992)

Conference Article| May 01 1992 Protein kinase C Peter J. Parker; Peter J. Parker 1Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX, U.K. Search for other works by this author on: This Site PubMed Google Scholar Paul P. Cook; Paul P. Cook *Department of Medicine, School of Medicine, East Carolina University, Greenville, North Carolina 27858–4354, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar Andrée R. Olivier; Andrée R. Olivier 1Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX, U.K. Search for other works by this author on: This Site PubMed Google Scholar Cathy Pears; Cathy Pears 1Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX, U.K. Search for other works by this author on: This Site PubMed Google Scholar D. Kirk Ways; D. Kirk Ways *Department of Medicine, School of Medicine, East Carolina University, Greenville, North Carolina 27858–4354, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar Catherine Webster Catherine Webster 1Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1992) 20 (2): 415–418. https://doi.org/10.1042/bst0200415 Article history Received: December 19 1991 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation Peter J. Parker, Paul P. Cook, Andrée R. Olivier, Cathy Pears, D. Kirk Ways, Catherine Webster; Protein kinase C. Biochem Soc Trans 1 May 1992; 20 (2): 415–418. doi: https://doi.org/10.1042/bst0200415 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: PKC, protein kinase C, DAG, deacylglycerol, TPA, tetradecanoyl phorbol acetate This content is only available as a PDF. © 1992 Biochemical Society1992 Article PDF first page preview Close Modal You do not currently have access to this content.
Hybrid remote quantum dot/powder phosphor designs for display backlights (2016)

Quantum dots are ideally suited for color conversion in light emitting diodes owing to their spectral tunability, high conversion efficiency and narrow emission bands. These properties are particularly important for display backlights; the highly saturated colors generated by quantum dots justify their higher production cost. Here, we demonstrate the benefits of a hybrid remote phosphor approach that combines a green-emitting europium-doped phosphor with red-emitting CdSe/CdS core/shell quantum dots. Different stacking geometries, including mixed and separate layers of both materials, are studied at the macroscopic and microscopic levels to identify the configuration that achieves maximum device efficiency while minimizing material usage. The influence of reabsorption, optical outcoupling and refractive index-matching between the layers is evaluated in detail with respect to device efficiency and cost. From the findings of this study, general guidelines are derived to optimize both the cost and efficiency of CdSe/CdS and other (potentially cadmium-free) quantum dot systems. When reabsorption of the green and/or red emission is significant compared to the absorption strength for the blue emission of the pumping light emitting diode, the hybrid remote phosphor approach becomes beneficial.
Abstract 1657: Tumor selective immunotherapy to overcome checkpoint blockade resistance (2021)

Abstract Most patients are resistant to PD-1/PD-L1 blockade therapy but mechanisms are not well defined. Defective innate sensing limits reactivation of T cells after the blockade. Patients with well-established solid tumors often generate complicated immunosuppressive networks and are generally refractory to immunotherapy. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a two-electron oxidoreductase elevated (more than 100-fold) in most solid cancers and has emerged as a promising target for direct tumor-killing. Here, we demonstrate that novel NQO1 targeting drug-Isobutyldeoxynyboquinone (IB-DNQ) causes tumor-selective innate sensing leading to T cell dependent tumor suppression. IB-DNQ treatment increases PD-L1 expression in the tumor microenvironment. Upregulated PD-L1 within TME contributes to tumor relapse and provides therapeutic window for combination therapy of IB-DNQ with immune checkpoint blockade. We demonstrate that IB-DNQ or PD-1 blockade treatment alone leads to tumor rejection in mice bearing small but not large established tumors. However, combination therapy of IB-DNQ with anti-PD-L1 eradicates well-established and checkpoint blockade refractory tumors. Citation Format: Lingxiang Jiang, Paul J. Hergenrother, Xiumei Huang. Tumor selective immunotherapy to overcome checkpoint blockade resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1657.
A retrospective analysis of upfront tandem autologous stem cell transplantation (ASCT) for high-risk (HR) myeloma (MM) patients (Pts). (2015)

e19532 Background: Previously, the median progression-free survival (PFS) and overall survival (OS) of MM pts with HR cytogenetics by FISH was ~9 mos and ~18 mos, respectively, after single ASCT (Chang H, Bone Marrow Transplant 2005; 36: 793). Since then, novel agents have been integrated before (often bortezomib [BTZ]) and after (often lenalidomide [len]) ASCT. We also offered upfront tandem ASCT for HR pts, and now retrospectively review the results of this approach. Methods: After IRB approval, HR pts who underwent upfront planned tandem ASCT were identified using the Princess Margaret Myeloma Database. Retrospective chart review was used to update pt outcomes. Results: Between 06/05 and 02/14, 38 HR pts underwent tandem ASCT at Princess Margaret Cancer Centre. 23 had del 17p, 17 had t(4;14), 4 had t(14;16), 3 had both t(4;14) + del 17p and 3 had both t(14;16) + del 17p. Median age was 56.5 yrs (range 31-71); 26 were male. ISS stage was I in 8, II in 14, III in 10 and N/A in 6 pts. Induction therapy was BTZ-based in 31 (CyBorD in 28); 9 pts required a 2nd regimen before ASCT. The median time from diagnosis to 1st ASCT was 6.3 mos (range 4.7 -27.9). The median time between transplants was 3.5 mos (range 1.0- 6.3); 16 pts received len between ASCTs to prevent early relapse. After the 2ndASCT, maintenance included thalidomide in 7, len +/- steroids in 25 and BTZ +/- len in 4 pts. No transplant-related deaths occurred. The PFS of the 4 pts with t(14;16) alone was 3.4+, 5, 14.6 and 19.2+ mos. Following progression after ASCT, the median survival of all 38 pts was 7.4 mos. Conclusions: 1) Although some pts experienced prolonged benefit, the median PFS and OS of pts with HR cytogenetics, particularly t(4;14), remains suboptimal even in the era of novel agents and tandem ASCT; 2) further analysis to identify pts who may benefit from tandem ASCT is underway. HR Group # Calculated from diagnosis Calculated from 2nd ASCT Median PFS, mos (range) Median OS, mos (range) Median PFS, mos (range) Median OS, mos (range) All 38 22.3 (9.0-77.4) 32.6 (11.9-105.2) 11.25 (1.26-63.6) 20.9 (3.8-94) t(4;14) 17 19.9 (13.2-47.2) 27.2 (17.9-84.3) 9.4 (3.2-23.4) 17.2 (6.9-73.6) Del 17p 23 24.3 (9.1-77.4) 34.7 (11.9-105.2) 12.5 (1.26-63.6) 25.3 (3.8-94)
Functional microRNAs in Alzheimer’s disease and cancer: differential regulation of common mechanisms and pathway (2013)

Two of the main research priorities in the United States are cancer and neurodegenerative diseases, which are attributed to abnormal patterns of cellular behavior. MicroRNAs (miRNA) have been implicated as regulators of cellular metabolism, and thus are an active topic of investigation in both disease areas. There is presently a more extensive body of work on the role of miRNAs in cancer compared to neurodegenerative diseases, and therefore it may be useful to examine whether there is any concordance between the functional roles of miRNAs in these diseases. As a case study, the roles of miRNAs in Alzheimer's disease (AD) and their functions in various cancers will be compared. A number of miRNA expression patterns are altered in individuals with AD compared with healthy older adults. Among these, some have also been shown to correlate with neuropathological changes including plaque and tangle accumulation, as well as expression levels of other molecules known to be involved in disease pathology. Importantly, these miRNAs have also been shown to have differential expression and or functional roles in various types of cancer. To examine possible intersections between miRNA functions in cancer and AD, we review the current literature on these miRNAs in cancer and AD, focusing on their roles in known biological pathways. We propose a pathway-driven model in which some molecular processes show an inverse relationship between cancer and neurodegenerative disease (e.g., proliferation and apoptosis) whereas others are more parallel in their activity (e.g., immune activation and inflammation). A critical review of these and other molecular mechanisms in cancer may shed light on the pathophysiology of AD, and highlight key areas for future research. Conclusions from this work may be extended to other neurodegenerative diseases for which some molecular pathways have been identified but which have not yet been extensively researched for miRNA involvement.
Colloidal Cu<sub>4</sub>I<sub>4</sub> Clusters for High-Resolution X-ray Imaging Scintillation Screens (2023)

Luminescent copper halide clusters have attracted wide attention in light-emitting diodes and optical sensors due to their intriguing physicochemical properties and diverse chemical structures. Recently, the clusters have also been explored as promising scintillation materials due to the heavy copper halide cores that provide a large absorption cross section for X-ray radiation. However, the related research on copper halide cluster scintillators is only in its infancy, and the scintillation performance of the clusters still lags behind that of perovskite and its related metal halide structures. Here we report 0D cubane-like Cu4I4(L)4 (L = 4-benzylpyridine or 4-tert-butylpyridine) clusters with broad emission band, high photoluminescence quantum yield (>85%), and a large Stokes shift. Density functional theory calculations demonstrate that the emission of both clusters mainly originates from the ligand-to-core charge transfer state. Besides, we successfully synthesized the colloidal cluster microcrystals and fabricated microcrystal-based films for X-ray imaging applications. We found that the cluster-based X-ray screens exhibited high light yields (>30000 photons MeV–1), low detection limits (<150 nGy s–1), and excellent spatial resolutions exceeding 20 lp mm–1, surpassing the resolution of the most common commercial scintillators. We believe that this work provides the foundation for the further development of high-performance copper cluster-based scintillators.
Threshold value for acceptable video quality using signal-to-noise ratio (2007)

Noise decreases video quality considerably, particularly in dark environments. In a video clip, noise can be seen as an unwanted spatial or temporal variation in pixel values. The object of the study was to find a threshold value for signal-to-noise ratio (SNR) in which the video quality is perceived to be good enough. Different illumination levels for video shooting were studied using both subjective and objective (SNR measurements) methodologies. Five camcorders were selected to cover different sensor technologies, recording formats and price categories. The test material for the subjective test was recorded in an environment simulator, where it was possible to adjust lighting levels. Double staircase test was used as the subjective test method. The test videos for objective measurements were recorded using an ISO 15739 based environment. There was a correlation found between objective and subjective measurements, between measured SNR and perceived quality. Good enough video quality was reached between SNR values of 15.3 dB and 17.2 dB. With 3CCD and super HAD-CCD technologies, video quality was brighter, less noisy, and the SNR was better in low light conditions compared to the quality with conventional CCDs.
Protein kinase C modulation of thermo-sensitive transient receptor potential channels: Implications for pain signaling (2011)

A variety of molecules are reported to be involved in chronic pain. This review outlines the specifics of protein kinase C (PKC), its isoforms and their role in modulating thermo-sensitive transient receptor potential (TRP) channels TRPV1-4, TRPM8, and TRPA1. Anatomically, PKC and thermo-sensitive TRPs are co-expressed in cell bodies of nociceptive dorsal root ganglion (DRG) neurons, which are used as physiological correlates of peripheral and central projections involved in pain transmission. In the past decade, modulation of painful heat-sensitive TRPV1 by PKC has received the most attention. Recently, PKC modulation of other newly discovered thermo-sensitive pain-mediating TRPs has come into focus. Such modulation may occur under conditions of chronic pain resulting from nerve damage or inflammation. Since thermo-TRPs are primary detectors of acute pain stimuli, their modulation by PKC can severely alter their function, resulting in chronic pain. Comprehensive knowledge of pain signaling involving interaction of specific isoforms of PKC with specific thermo-sensitive TRP channels is incomplete. Such information is necessary to dissect out modality specific mechanisms to better manage the complex polymodal nature of chronic pain. This review is an attempt to update the readers on current knowledge of PKC modulation of thermo-sensitive TRPs and highlight implications of such modulation for pain signaling.
Motor skill depends on knowledge of facts (2013)

Those in 20th century philosophy, psychology, and neuroscience who have discussed the nature of skilled action have, for the most part, accepted the view that being skilled at an activity is independent of knowing facts about that activity, i.e., that skill is independent of knowledge of facts. In this paper we question this view of motor skill. We begin by situating the notion of skill in historical and philosophical context. We use the discussion to explain and motivate the view that motor skill depends upon knowledge of facts. This conclusion seemingly contradicts well-known results in cognitive science. It is natural, on the face of it, to take the case of H.M., the seminal case in cognitive neuroscience that led to the discovery of different memory systems, as providing powerful evidence for the independence of knowledge and skill acquisition. After all, H.M. seems to show that motor learning is retained even when previous knowledge about the activity has been lost. Improvements in skill generally require increased precision of selected actions, which we call motor acuity. Motor acuity may indeed not require propositional knowledge and has direct parallels with perceptual acuity. We argue, however, that reflection on the specifics of H.M.'s case, as well as other research on the nature of skill, indicates that learning to become skilled at a motor task, for example tennis, depends also on knowledge-based selection of the right actions. Thus skilled activity requires both acuity and knowledge, with both increasing with practice. The moral of our discussion ranges beyond debates about motor skill; we argue that it undermines any attempt to draw a distinction between practical and theoretical activities. While we will reject the independence of skill and knowledge, our discussion leaves open several different possible relations between knowledge and skill. Deciding between them is a task to be resolved by future research.
Diagnostic de piles à combustible en utilisant la transformée en ondelettes (2015)

International audience
Abstract 2521: Targeting CD44 in head and neck squamous cell carcinoma (HNSCC) with a new humanized antibody RO5429083 (2012)

Abstract Introduction: HNSCC is a debilitating and deadly disease for which current treatments are extremely toxic and ineffective. Increasing data suggest that persistent cancer stem cells (CSC), resistant to standard chemo and radiation therapy, give rise to disease recurrence. Thus, poor outcomes may reflect ineffective CSC killing. CD44 is a promising therapeutic target that has two defined roles in tumorigenesis: it is a putative cancer initiating cell or CSC marker and it promotes migration and proliferation through interaction with EGFR, Rho and Ras signaling. Therefore therapies that target CD44 may destroy the CSC population, which is resistant to therapy while precisely eradicating the proliferating population of cancer cells. Methods: RO5429083 is a novel functional monoclonal antibody, developed by Roche, that targets a glycosylated, conformation dependent epitope of CD44. To evaluate CD44 as a therapeutic target in vivo, we established CAL 27 (HNSCC cell line) xenografts in nude mice and treated them with RO5429083 (Roche) in comparison to cisplatin (DPP), a conventional drug used in HNSCC treatment. After treatment, the mice were sacrificed, and the tumors were embedded in paraffin for IHC analysis. We also analyzed the effect of RO5429083 in vitro on peripheral blood lymphocytes (PBMCs). Results: RO5429083 treatment displayed a remarkable tumor growth inhibition in CAL 27 xenografts compared to DPP or control (P&amp;lt;0.005). Moreover, treatment with this new humanized antibody inhibited constitutive EGFR phosphorylation on CAL 27 xenografts. In addition, treatment of PBMCs from healthy donors with RO5429083 produced an expansion of cytolytic natural killer (NK) cells. Conclusion: Based on our studies the anti-CD44 antibody RO5429083 effectively inhibits tumor growth in the CAL 27 model of HNSCC. In addition to decreasing EGFR signaling, RO5429083 appears to have a protective effect on PBMCs and expands the NK cell population. In conclusion, we anticipate that anti-CD44 therapy will effectively target the stem cell population while boosting the number of NK cells, and thus may synergize with drugs that work via antibody-dependent cell-mediated cytotoxicity (ADCC) such as Cetuximab. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2521. doi:1538-7445.AM2012-2521
Spectral responses of virtual Frisch-grid CdZnTe detectors and their relation to IR microscopy and x-ray diffraction topography data (2008)

Virtual Frisch-grid CdZnTe detectors potentially can provide energy resolution close to the statistical limit. However, in real detectors, the quality of the crystals used to fabricate the devices primarily determines energy resolution. In this paper, we report our findings on the spectral response of devices and their relation to material-characterization data obtained using IR microscopy and X-ray diffraction topography.
Oncolytic ImmunoViroTherapy: A long history of crosstalk between viruses and immune system for cancer treatment (2021)

Cancer Immunotherapy relies on harnessing a patient's immune system to fine-tune specific anti-tumor responses and ultimately eradicate cancer. Among diverse therapeutic approaches, oncolytic viruses (OVs) have emerged as a novel form of cancer immunotherapy. OVs are a naturally occurring or genetically modified class of viruses able to selectively kill cancer cells, leaving healthy cells unharmed; in the last two decades, the role of OVs has been redefined to act beyond their oncolytic activity. Indeed, the immunogenic cancer cell death mediated by OVs induces the release of tumor antigens that in turn induces anti-tumor immunity, allowing OVs to act as in situ therapeutic cancer vaccines. Additionally, OVs can be engineered for intratumoral delivery of immunostimulatory molecules such as tumor antigens or cytokines to further enhance anti-tumor response. Moreover, OVs can be used in combination with other cancer immunotherapeutic approaches such as Immune Checkpoint Inhibitors and CAR-T cells. The current review first defines the three main mechanisms of action (MOA) of OVs currently used in cancer therapy that are: i) Oncolysis, ii) OV-induced cancer-specific immune activation, and iii) Exploiting pre-existing anti-viral immunity to enhance cancer therapy. Secondly, we focus on how OVs can induce and/or improve anti-cancer immunity in a specific or unspecific fashion, highlighting the importance of these approaches. Finally, the last part of the review analyses OVs combined with other cancer immunotherapies, revising present and future clinical applications.
Drillstring Vibration Observation, Modeling and Prevention in the Oil and Gas Industry (2014)

As well designs become increasingly complicated, a complete understanding of drillstring vibrations is key to maximize drilling efficiency and reduce bit wear as well as prevent drillstring, tool, and borehole damage. This paper presents a review of the past fifty years of work on drillstring dynamics models and the proposed and accepted vibration mitigation applications within the drilling industry. Early modeling began with simplistic models in efforts to understand downhole processes. Once downhole sensors were deployed and the basic modes of vibration were understood, proprietary systems were developed and — only recently — successfully deployed to detect and mitigate the effects of certain undesired vibrational modes, specifically stick-slip torsional vibrations. Future systems and their effectiveness will depend on a refined understanding of the various modes of vibration and their interaction, as well as improved real-time downhole sensing techniques. Implementation of high-fidelity models to deduce and correct the downhole drillstring state will subsequently improve the operational drilling efficiency.