gebhart/patrepeval huggingface dataset:
Driving cars to the clinic for solid tumors (2018)

FDA approval of chimeric antigen receptor T cells (CART cells) is the culmination of several decades of technology development and interrogation of the properties of these gene therapies. CART cells exist as personalized "living drugs" and have demonstrated astounding anti-tumor efficacy in patients with leukemia and lymphoma. However, the future promise of CART efficacy for solid tumors, the greatest unmet burden, is met with a number of challenges that must be surmounted for effective immune responses. In this review, we discuss the next-generation developments of CARs to target solid tumors, including fine-tuned and combinational-targeting receptors. We consider the structural intricacies of the CAR molecules that influence optimal signaling and CART survival, and review pre-clinical cell-intrinsic and cell-extrinsic combinational therapy approaches.
IDDF2020-ABS-0215 Enhancer reprogramming by selective HDAC8 inhibition potentiates tumor remission and durable benefit by PD-L1 blockade (2020)

<h3>Background</h3> The insufficient T cell infiltration into non-inflamed tumors such as hepatocellular carcinoma (HCC) restricts the effectiveness of immune-checkpoint blockade (ICB) to a minority of patients. Epigenetic therapy provides new opportunities to rewire cancer transcriptional programs, but whether and how selective epigenetic inhibition counteracts the immune-excluded phenotype to sensitize ICB therapy remain incompletely defined. Here, we aimed to investigate the therapeutic efficacy and mechanistic basis of histone deacetylase 8 (HDAC8), a histone H3 lysine 27 (H3K27)-specific isoform, in HCC development and ICB responsiveness. <h3>Methods</h3> The immune-modulatory and anti-tumor effects of HDAC8 inhibition via a HDAC8-selective inhibitor, PCI34051, were determined in orthotopic HCC mouse models. Molecular mechanisms and functional significance of HDAC8 inhibition were conducted by genome-wide H3K27ac ChIP-seq and RNAseq in HCC patient specimens, cancer cell lines, NOD-SCID and humanized mouse models. The efficacy of single or combined therapy with anti-programmed death-1-ligand-1 (anti-PD-L1) and PCI34051 was determined in orthotopic and spontaneous HCC mouse models. <h3>Results</h3> Pharmacological inhibition of HDAC8 thwarted HCC tumorigenicity in immunocompetent but not immunodeficient mice. The tumor-suppressive effect of PCI34051 was abrogated by CD8<sup>+</sup>T cell depletion or regulatory T cell adoptive transfer. Chromatin profiling of human HDAC8-expressing HCCs revealed genome-wide H3K27 deacetylation in 1,251 silenced enhancer-target gene pairs that were enriched in metabolic and immune regulators. Mechanistically, down-regulation of HDAC8 increased global and enhancer levels of H3K27 acetylation to reactivate T cell-trafficking chemokine production from HCC cells, thus relieving T cell exclusion in both NOD-SCID and humanized mouse models. In the HCC preclinical model, selective HDAC8 inhibition significantly increased tumor-infiltrating CD8<sup>+</sup>T cells and potentiated eradication of established hepatoma by anti-PD-L1 therapy without a sign of toxicity. Importantly, mice treated with HDAC8/PD-L1 co-blockade were protected against subsequent tumor re-challenge with the induction of memory T cells and remained tumor-free for ≥15 months. <h3>Conclusions</h3> Our study demonstrates that selective HDAC8 inhibition elicits effective and durable ICB responses by co-opting adaptive immunity via enhancer reprogramming, thereby providing a new strategy for effective combined epigenetic immunotherapy.
EELS Analysis of Bulk Plasmon Harmonics of Aluminium at 30 keV (2018)

EELS is especially useful for the detection of light elements, since these elements have ionization edges of low energy High-energy STEM-EELS has been used for the positive identification of lithium in lithium-copper precipitates in Al-2099, as a complement to low energy back-scattered electron (BSE) microscopy and X-ray energy dispersive spectroscopy (EDS)
Supplementary Figures S1-S4 from Eribulin Induces Irreversible Mitotic Blockade: Implications of Cell-Based Pharmacodynamics for <i>In vivo</i> Efficacy under Intermittent Dosing Conditions (2023)

&lt;p&gt;Supplementary Figures S1-S4.&lt;/p&gt;
Captopril-induced deterioration of graft function in patients with a transplant renal artery stenosis. (1983)

We evaluated nine captopril-treated patients with transplant renal artery stenosis. Captopril treatment always resulted in a dramatic decrease in renal function; in two patients complete anuria developed. Only in two patients with a stenosis in one out of two renal arteries was a satisfactory fall in blood pressure achieved. The mechanisms which may lead to these remarkable results will be discussed.
Ultrathin flexible nanocomposite membranes as miniature pressure sensors (2009)

Measuring microscopic deflections of membranes caused by small changes in pressure, weight, temperature, or chemical interactions is developing into one of the most versatile sensing approaches. Ultra-thin membranes are emerging as critical elements in various sensing devices, such as acoustic, pressure microdevices, chemical and thermal sensors, all discussed in this paper.
General measures for signal-noise separation in nonlinear dynamical systems (2000)

We propose the straight phi divergences from statistics and information theory (IT) as a set of separation indices between signal and noise in stochastic nonlinear dynamical systems (SNDS). The straight phi divergences provide a more informative alternative to the signal-to-noise ratio (SNR) and have the advantage of being applicable to virtually any kind of stochastic system. Moreover, straight phi divergences are intimately connected to various fundamental limits in IT. Using the properties of straight phi divergences, we show that the classical stochastic resonance (SR) curve can be interpreted as the performance of a nonoptimal, or mismatched, detector applied to the output of a SNDS. Indeed, for a prototype double-well system with forcing in the form of white Gaussian noise plus a possible embedded signal, the whole information loss can be attributed to this mismatch; an optimal detection procedure (for the signal) gives the same performance when based on the output as when based on the input of the system. More generally, it follows that, when characterizing signal-noise separation (or system performance) of SNDS in terms of criteria that do not correspond to IT limits, the choice of criterion can be crucial. The indicated figure of merit will then not be universal and will be relevant only to some family of applications, such as the classical (narrow-band SNR) SR criterion, which is relevant for narrow-band post processing. We illustrate the theory using simple SNDS excited by both wide- and narrow-band signals; however, we stress that the results are applicable to a much larger class of signals and systems.
A human thymus-leukemia antigen defined by hybridoma monoclonal antibodies. (1979)

A series of mouse hybridomas producing monoclonal antibodies against human acute lymphocytic leukemia (ALL) cells was generated and screened for tumor specificity. Among 1200 primary cultures, 60 produced an antibody that could distinguish between the immunizing leukemia cells and an isologous B lymphoblastoid cell line. Of these, two produced an antibody that detects an antigen expressed preferentially on ALL cells and on a subpopulation of normal cells found in the cortex of the thymus. Other normal human lymphoid cells from lymph nodes, spleen, bone marrow, and peripheral blood express only low levels of this antigen. High levels of this "thymus-leukemia" antigen were found on T-ALL cells, T-ALL-derived cell lines, and some "null" ALL cells. By contrast, B-cell leukemias, B lymphoblastoid cell lines, and normal and malignant myeloid cells contain either low or undetectable amounts of this antigen. The thymus-leukemia antigen has been isolated from the membranes of leukemia cells by detergent solubilization and subsequent immunoprecipitation with the monoclonal antibody. Preliminary biochemical characterization shows the antigen to be associated with a polypeptide of Mr approximately 28,000.
Macroscopic In Vivo Imaging of Facial Nerve Regeneration in Thy1 - GFP Rats (2014)

NA.
Si-passivated Ge nMOS gate stack with low Dit and dipole-induced superior PBTI reliability using 3D-compatible ALD caps and high-pressure anneal (2016)

We demonstrate a Si-passivated Ge nMOS gate stack with D <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">IT</sub> of ~5×10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">10</sup> cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-2</sup> eV <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> around midgap and unnoticeable C-V hysteresis at an operating condition (oxide trap density of ~1×10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">8</sup> cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-2</sup> at V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ov</sub> /CET=3.5 MV/cm). Insertion of a 3D-compatible thin ALD LaO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sub> , MgO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sub> and LaSiO layer at the interface between HfO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> and SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> /Si/Ge improves PBTI reliability thanks to the interface dipole-induced band engineering. The high D <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">IT</sub> of Si-passivated Ge nFET is dramatically reduced by ~40x around midgap using a combination of the LaSiO insertion and a H <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> high-pressure anneal (HPA). These key gate stack technologies realize further improvements in mobility (~50% at peak) and PBTI reliability (V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ov</sub> =0.32 V for 10 years) of Si-passivated Ge nFETs.
Suppl. Fig. 3: Illustration of the applied thresholding. from Combined PET Imaging of the Inflammatory Tumor Microenvironment Identifies Margins of Unique Radiotracer Uptake (2023)

&lt;p&gt;(A) An elliptical VOI (yellow) was drawn in the striatum. (B) Another elliptical VOI (green) was placed over the affected hemisphere. (C) After application of a thresholding based on the control VOI. The same original VOIs (left and middle) were used for all animals for individual thresholding.&lt;/p&gt;
Pathogenesis of Ovarian Serous Carcinoma as the Basis for Immunologic Directed Diagnosis and Treatment (2003)

Abstract : The purpose of this study is to elucidate the pathogenesis of serous carcinoma by identifying the molecular genetic changes and preferentially expressed genes of different histological types of serous neoplasms. We hypothesize that the development of serous carcinoma proceeds along two main pathways: one is rapid progression from ovarian surface epithelium to high-grade serous carcinoma without well-established morphological precursors (de novo pathway) and the other is a gradual development from borderline tumors to non-invasive micropapillary serous carcinomas then to low- grade carcinomas (stepwise pathway). The first pathway results in a high-grade neoplasm (conventional serous carcinoma) and the second leads to the development of a low-grade indolent tumor. Both types of carcinomas and the putative precursor lesions of invasive MPSC are characterized by distinctive molecular genetic alterations and specific gene expression. We identified that mutations in KRAS/BRAF/ERRB2 genes characterized the development of low- grade serous carcinomas. Expression of HLA-G apoE and membralin molecules were confined to high-grade serous carcinomas. This project designed to test our proposed model of diverse pathways in the pathogenesis of ovarian serous carcinoma provides an etiologic basis for the other two projects.
Mouse ether (2004)

When acquiring a target located on a different screen, multi-monitor users face a challenge: differences in resolution and vertical and horizontal offsets between screens cause the mouse pointer to get warped, making the attempt to acquire the target difficult. Mouse ether eliminates warping effects by applying appropriate transformations to all mouse move events. In our user study, mouse ether improved participants' performance on a target acquisition task across two screens running at different resolutions by up to 28%. 7 of the 8 participants also strongly preferred using mouse ether to the control.
Supplementary Figure 4 from Identification of Existing Drugs That Effectively Target <i>NTRK1</i> and <i>ROS1</i> Rearrangements in Lung Cancer (2023)

&lt;p&gt;Chemical structures of lead compounds&lt;/p&gt;
Acoustic microscope visualization and thickness measurements of deep internal layers in layered polymer systems (2002)

A method of investigation of the structure, properties and geometrical parameters of highly absorptive polymer multilayered media using short pulse scanning acoustic microscopy is described. The possibility of successful evaluation and visualization of internal layers having 3% of the total thickness of a sample is demonstrated. A time domain digital processing algorithm is developed to provide a precise thickness measurement of each layer in the layered polymer.
Precision of nitrogen dioxide photolysis rate measurements (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPrecision of nitrogen dioxide photolysis rate measurementsRussell R. Dickerson and Donald H. StedmanCite this: Environ. Sci. Technol. 1980, 14, 10, 1261–1262Publication Date (Print):October 1, 1980Publication History Published online1 May 2002Published inissue 1 October 1980https://pubs.acs.org/doi/10.1021/es60170a015https://doi.org/10.1021/es60170a015research-articleACS PublicationsRequest reuse permissionsArticle Views438Altmetric-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
Broadband point-spread function engineering via a freeform diffractive microlens array (2021)

We utilized inverse design to engineer the point-spread function (PSF) of a low-f-number, freeform diffractive microlens in an array, so as to enable extended depth of focus (DOF). Each square microlens of side 69 µm and focal length 40 µm (in a polymer film, n∼1.47) generated a square PSF of side ∼10 µm that was achromatic over the visible band (450 to 750 nm), and also exhibited an extended DOF of ∼ ± 2 µm. The microlens has a geometric f/# (focal length divided by aperture size) of 0.58 in the polymer material (0.39 in air). Since each microlens is a square, the microlens array (MLA) can achieve 100% fill factor. By placing this microlens array (MLA) directly on a high-resolution print, we demonstrated integral imaging with applications in physical security. The extended DOF preserves the optical effects even with expected film-thickness variations, thereby increasing robustness in practical applications. Since these multi-level diffractive MLAs are fabricated using UV-nanoimprint lithography, they have the potential for low-cost large volume manufacturing.
FcγRIII Is Protective against Pseudomonas aeruginosa Pneumonia (2007)

Defenses against bacterial infections involve activation of multiple systems of innate immunity, including complement, Toll-like receptors, and defensins. Reactions to chronic infections bring adaptive immune mechanisms into play as well, with the introduction of modulatory interactions between the two. In humans with chronic lung infections, the severity of inflammation and disease correlate with elevated levels of pathogen-specific immune complexes and complement activation. In mice with genetic deficiency in C5, or targeted deletion of the C5a receptor, Pseudomonas lung infections reveal a role for the C5a anaphylatoxin in disease severity. Deficient animals exhibit significantly reduced survival and clearance of infecting bacteria, simultaneous with greatly increased pulmonary influx of inflammatory cells. Among the actions of C5a on inflammatory cells mediated through the C5a receptor is a shift in the relative expression of Fcgamma receptors to increase FcgammaRIII relative to FcgammaRII. This shift may significantly impact defenses against chronic infection, reflecting the cellular activation profiles of these IgG receptors. We addressed the role of FcgammaRIII in defense against Pseudomonas lung infection, and found that, like C5aR-deficient mice, animals with targeted deletion of FcgammaRIII are more susceptible to mortality upon infection and exhibit reduced clearance of the pathogen. Pseudomonas infection was associated with an increase in the FcgammaRIII/FcgammaRII ratio in wild-type mice, and the data support its role as an additional mechanism of host defense against bacterial infection.
TCR Affinity Associated with Functional Differences between Dominant and Subdominant SIV Epitope-Specific CD8+ T Cells in Mamu-A*01+ Rhesus Monkeys (2014)

Many of the factors that contribute to CD8+ T cell immunodominance hierarchies during viral infection are known. However, the functional differences that exist between dominant and subdominant epitope-specific CD8+ T cells remain poorly understood. In this study, we characterized the phenotypic and functional differences between dominant and subdominant simian immunodeficiency virus (SIV) epitope-specific CD8+ T cells restricted by the major histocompatibility complex (MHC) class I allele Mamu-A*01 during acute and chronic SIV infection. Whole genome expression analyses during acute infection revealed that dominant SIV epitope-specific CD8+ T cells had a gene expression profile consistent with greater maturity and higher cytotoxic potential than subdominant epitope-specific CD8+ T cells. Flow-cytometric measurements of protein expression and anti-viral functionality during chronic infection confirmed these phenotypic and functional differences. Expression analyses of exhaustion-associated genes indicated that LAG-3 and CTLA-4 were more highly expressed in the dominant epitope-specific cells during acute SIV infection. Interestingly, only LAG-3 expression remained high during chronic infection in dominant epitope-specific cells. We also explored the binding interaction between peptide:MHC (pMHC) complexes and their cognate TCRs to determine their role in the establishment of immunodominance hierarchies. We found that epitope dominance was associated with higher TCR:pMHC affinity. These studies demonstrate that significant functional differences exist between dominant and subdominant epitope-specific CD8+ T cells within MHC-restricted immunodominance hierarchies and suggest that TCR:pMHC affinity may play an important role in determining the frequency and functionality of these cell populations. These findings advance our understanding of the regulation of T cell immunodominance and will aid HIV vaccine design.
Studies on Nanosized Iron Based Modified Catalyst for Fischer-Tropsch Synthesis Application (2011)

To improve catalytic performance iron based catalyst, the effects of some metal promoters, especially potassium, copper and other transition metal oxides as well as different supports have been reported. A series of Fe/K/Cu catalysts promoted with magnesium and ceria by precipitation method, followed by impregnation method; keeping Cu and K content same. The catalysts were characterized by XRD, N2 physisorption, TPR and TEM techniques. From XRD, the presence of hematite (Fe2O3) phase was detected in all precipitated iron catalysts and CFe2.5 phase in all used catalysts. TPR results showed that addition of Mg facilitated the reduction of Fe2O3 and decrease in reduction temperature. The catalytic performance was investigated in a fixed-bed reactor at 250 degrees C, 2 MPa pressure and H2/CO molar ratio of 2. Concentration of Mg was found to affect the CO conversion and product distribution. It was found that precipitated iron catalyst Fe/Mg/Cu/K with Mg/Fe ratio of 0.1 showed highest conversion (60.6%) and C5(+) selectivity (92.4%) among all catalysts tested.
Proteomic Analysis of Pathways Involved in Estrogen-Induced Growth and Apoptosis of Breast Cancer Cells (2011)

G-protein-coupled receptors, PI3 kinase, Wnt and Notch signaling pathways were most strongly associated with E2-induced proliferation or apoptosis and are integrated here into a global AIB1 signaling network that controls qualitatively distinct responses to estrogen.
A quick AND/OR search for multimedia signals based on histogram features (2003)

Abstract The problem of finding the point in time at which a known audio or video source (reference signal) appears in a long audio or video source (input signal) is referred to as a time series search, in contrast to a text string search. In a time series search, a search can be performed quickly by combining the audio and video, and then identifying several search conditions using logical equations. Thus, in this paper the authors describe the application of the time series active search method, a method to search audio signals proposed in the authors' previous paper, to video searches. Next, the authors propose an efficient algorithm for AND searches and OR searches of reference signals. In addition, the authors propose a multimodal AND search which combines audio and video. The proposed algorithms are faster than combining the results of searches performed individually. For instance, in an OR search of a reference signal, when the mutual similarity in the reference signals is above 0.8, five reference signals can be searched in a search time that is 1.2 times faster than searching one reference signal. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 86(12): 54–64, 2003; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/ecjc.10142
Microdissection and Extraction of DNA From Archival Tissue (2004)

Microdissection of cells with distinct histological features from tissue sections has become important because of the development of sensitive genetic techniques. This is of particular importance when analyzing genetic differences in tumor tissue compared to normal tissue. Failure to separate normal and tumor cell types can result in masking of results, false results, and discrepancies between repeat experiments. For example, use of polymerase chain reaction (PCR) to identify loss of heterozygosity or mutations in tumor cell DNA may be missed without use of microdissection, as the DNA from normal cell population may dilute out the DNA from the tumor cells.