gebhart/patrepeval huggingface dataset:
Abstract 564: Combination therapy of chemokine receptor inhibition plus PD-L1 blockade potentiates antitumor effects in a murine model of breast cancer (2016)

Abstract Trafficking and expansion of myeloid derived suppressor cells (MDSCs) plays a major role in the immune suppression of tumors. MDSCs express chemokine receptors which likely mediate their recruitment to the tumor microenvironment. Suppression of T cells is also mediated by the interaction of programmed death-1 (PD-1) and its ligands which are abundantly expressed in cancer cells and immune infiltrates, including MDSCs. Here, we show that targeting both pathways through administration of a small molecule chemokine receptor antagonist (CCX9588, which blocks CCR1) and a PD-L1 monoclonal antibody (mAb) significantly reduced tumor burden in mice who received orthotopic transplants of 4T1 cells, a cell line used to model triple negative breast cancer. Primary tumor growth was modestly reduced by either agent (PD-L1 mAb or CCR1 inhibitor) alone, but the combination of CCR1 inhibitor plus PD-L1 mAb resulted in significantly reduced tumor progression as compared to either of the single agents. Furthermore, lung metastasis was also significantly reduced by CCR1 antagonist and combination treatment. Orthotropic 4T1 cell engraftment induced robust expansion of CD11b+Ly6Ghi Ly6Chi MDSCs, a subpopulation of which express CCR1. Analysis of the tumor infiltrating cells revealed that CCX9588 significantly reduced the number of MDSCs and increased CD8 T cells infiltration in primary tumors, suggesting that CCR1 blockade of MDSC trafficking in combination with PD-L1 mAb translates into reduced tumor burden, possibly through increased CD8 T cell response against the tumor. Analysis of human breast cancer patient samples from The Cancer Genome Atlas (TCGA) database revealed that the CCR1 ligands, MCP-7 (CCL7) and RANTES (CCL5) are present at significantly higher levels in breast cancers as compared to normal breast tissue. Interestingly, ligands for CCR1 and PD-1 are significantly higher in triple negative breast cancer samples than in the other breast cancer subtypes. These data are the first to show that CCR1 chemokine receptor antagonists can act synergistically with PDL-1 inhibitors, and suggest a novel approach for potentiating the activity of immune cell checkpoint inhibitors in one of the most aggressive forms of breast cancer. Citation Format: Heiyoun Jung, Linda Ertl, Karen Ebsworth, Christine Janson, Penglie Zhang, Punna Sreenivas, Thomas Schall, Israel Charo. Combination therapy of chemokine receptor inhibition plus PD-L1 blockade potentiates antitumor effects in a murine model of breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 564.
Matrix Permittivity Measurements for Rock Powders (2014)

Abstract Formation water content is one of the key petrophysical quantities provided by dielectric logging. However, to determine water content from formation permittivity measurements the rock matrix permittivity must be known. Uncertainty in the rock matrix permittivity values translates into uncertainty in the water content estimate, which is especially important in low-porosity formations or complex lithologies. Matrix permittivity values are not well known for a number of minerals and can also vary for the same type of mineral in different formations. Thus, a laboratory methodology for the accurate determination of matrix permittivity at dielectric logging frequencies is required to facilitate accurate log interpretation. Matrix permittivity values can be measured on solid plugs (Seleznev et al., 2011). However, the plug-based methodology can be challenging in very low-permeability or unconventional reservoirs because of difficulties with plug drying. In addition, it is not readily applicable to unconsolidated formations. Finally, it may be impossible to cut solid plugs due to limited availability of rock material. Matrix permittivity measurements made on rock powders are capable of addressing all of these issues. We introduce a methodology for laboratory measurements of matrix permittivity on rock powders at 1 GHz. The methodology is based on conducting dielectric measurements on mixtures of rock powders and liquids with variable permittivities in a dielectric resonator. The permittivity of the rock matrix is inverted from a series of measurements obtained on pure liquids and powder-liquid mixtures. The methodology was benchmarked on a collection of samples representing common oilfield lithologies with matrix permittivity values between 4.6 and 8.6. The reference matrix permittivity values were first measured on solid plugs. Then the plugs were crushed into powders and the matrix permittivity values were determined on powders following the proposed methodology. The values obtained on powders matched the ones measured on solid plugs within 0.2 dielectric units resulting in accuracies better than 1% for the water-filled porosity and better than 1000 ppm for water salinity. This new methodology was applied to a number of core samples from a carbonate reservoir, offshore Sarawak where dielectric logging had been performed along with conventional core analysis. The resulting measured matrix permittivity values were then used to interpret the dielectric log measurement. Results showed a better estimation of water filled porosity and of the textural MN parameter than would have resulted from using ‘chartbook’ values of matrix permittivity. A consistent and optimized interpretation was obtained in porosities ranging from 5% to more than 30%.
Improvement of mammographic mass characterization using spiculation measures and morphological features (2001)

We are developing new computer vision techniques for characterization of breast masses on mammograms. We had previously developed a characterization method based on texture features. The goal of the present work was to improve our characterization method by making use of morphological features. Toward this goal, we have developed a fully automated, three-stage segmentation method that includes clustering, active contour, and spiculation detection stages. After segmentation, morphological features describing the shape of the mass were extracted. Texture features were also extracted from a band of pixels surrounding the mass. Stepwise feature selection and linear discriminant analysis were employed in the morphological, texture, and combined feature spaces for classifier design. The classification accuracy was evaluated using the area Az under the receiver operating characteristic curve. A data set containing 249 films from 102 patients was used. When the leave-one-case-out method was applied to partition the data set into trainers and testers, the average test Az for the task of classifying the mass on a single mammographic view was 0.83 +/- 0.02, 0.84 +/- 0.02, and 0.87 +/- 0.02 in the morphological, texture, and combined feature spaces, respectively. The improvement obtained by supplementing texture features with morphological features in classification was statistically significant (p = 0.04). For classifying a mass as malignant or benign, we combined the leave-one-case-out discriminant scores from different views of a mass to obtain a summary score. In this task, the test Az value using the combined feature space was 0.91 +/- 0.02. Our results indicate that combining texture features with morphological features extracted from automatically segmented mass boundaries will be an effective approach for computer-aided characterization of mammographic masses.
Abstract 2821: The PKC-iota inhibitor ICA-1 overcomes chemoresistance and induces cell death in glioblastoma multiforme (2012)

Abstract Glioblastoma multiforme is a very aggressive brain cancer that is refractory to most chemotherapeutics. The standard of care for glioblastoma patients is the administration of temozolomide following surgery. However, temozolomide provides an approximately 20% enhanced survival rate. Therefore, it is imperative to develop other novel chemotherapeutics to better enhance the survival rate and induce tumor regression in patients. A potential candidate for a pre-clinical glioblastoma study is the novel chemotherapeutic, ICA-1. ICA-1 is a PKC-iota inhibitor which specifically inhibits PKC-iota and not its homologue, PKC-zeta. Results demonstrated that ICA-1 inhibited cell proliferation rates in a range of T98G glioblastoma concentrations in vitro. Also, results showed that low density T98G cultures which have a high proliferation status and high S-phase promotion concomitantly demonstrated resistance to ICA-1 treatment. However, high density T98G cultures which have a lower proliferation status and low S-phase promotion are concurrently chemosensitive toward ICA-1. At 48h post ICA-1 treatment, the majority of cells in the high density cultures were in G0/G1 with a rise of cells in this phase of the cell cycle shown by day 5 post-treatment. Conversely, between 48h and day 5, 30-44% of cells from the low density cultures were in S phase irrespective of ICA-1 therapy. Furthermore, by day 5 post-treatment, ICA-1 induced significant cell death in T98G cells only at higher ranges (i.e., 20-40 microM of ICA-1). Interestingly, 40 microM ICA-1 caused a significant cell death rate of 45% when 7,500 cells were seeded into a 24-well plate on Day 0 followed by ICA-1 exposure on the next day. Forty microM ICA-1 induced 15% cell death when 3,750 cells were seeded. There was a stepwise increase in the amount of ICA-1 required to induce cell death as the cell concentration increased (i.e., high density T98G cultures required elevated levels of ICA-1). Therefore, the data suggested that the G0/G1 phase glioblastoma cells (i.e., the higher cell concentrations) were more sensitive to 40 microM ICA-1 therapy. Whereas, the S phase glioblastoma cells were less sensitive to the ICA-1 therapy. Future animal models may show that the more aggressive the tumor becomes, the greater the potential for the effectiveness of ICA-1 (i.e., greater chemosensitivity). 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 2821. doi:1538-7445.AM2012-2821
Modulation of the Substitution Pattern of 5-Aryl-2-Aminoimidazoles Allows Fine-Tuning of Their Antibiofilm Activity Spectrum and Toxicity (2016)

We previously synthesized several series of compounds, based on the 5-aryl-2-aminoimidazole scaffold, that showed activity preventing the formation of Salmonella enterica serovar Typhimurium and Pseudomonas aeruginosa biofilms. Here, we further studied the activity spectrum of a number of the most active N1- and 2N-substituted 5-aryl-2-aminoimidazoles against a broad panel of biofilms formed by monospecies and mixed species of bacteria and fungi. An N1-substituted compound showed very strong activity against the biofilms formed by Gram-negative and Gram-positive bacteria and the fungus Candida albicans but was previously shown to be toxic against various eukaryotic cell lines. In contrast, 2N-substituted compounds were nontoxic and active against biofilms formed by Gram-negative bacteria and C. albicans but had reduced activity against biofilms formed by Gram-positive bacteria. In an attempt to develop nontoxic compounds with potent activity against biofilms formed by Gram-positive bacteria for application in antibiofilm coatings for medical implants, we synthesized novel compounds with substituents at both the N1 and 2N positions and tested these compounds for antibiofilm activity and toxicity. Interestingly, most of these N1-,2N-disubstituted 5-aryl-2-aminoimidazoles showed very strong activity against biofilms formed by Gram-positive bacteria and C. albicans in various setups with biofilms formed by monospecies and mixed species but lost activity against biofilms formed by Gram-negative bacteria. In light of application of these compounds as anti-infective coatings on orthopedic implants, toxicity against two bone cell lines and the functionality of these cells were tested. The N1-,2N-disubstituted 5-aryl-2-aminoimidazoles in general did not affect the viability of bone cells and even induced calcium deposition. This indicates that modulating the substitution pattern on positions N1 and 2N of the 5-aryl-2-aminoimidazole scaffold allows fine-tuning of both the antibiofilm activity spectrum and toxicity.
A hybrid digital holographic microscopy for biological applications (2015)

It will be useful in biological applications if two or more physical parameters are simultaneously measured in a digital holographic microscope. In this paper, we present a hybrid digital holographic microscope that can measure simultaneously three-dimensional (3D) phase and 3D fluorescence distributions. This property has big advantage compared with conventional optical microscopes such as phase contrast microscope and fluorescence microscope. We present an optical setup for measuring both phase and fluorescence images. In the experiments, two objects that are fluorescence beads and egera densa are used. The separation method of phase and fluorescence images is presented.
Flash lamp-excited time-resolved fluorescence microscope suppresses autofluorescence in water concentrates to deliver an 11-fold increase in signal-to-noise ratio (2004)

The ubiquity of naturally fluorescing components (autofluorophores) encountered in most biological samples hinders the detection and identification of labeled targets through fluorescence-based techniques. Time-resolved fluorescence (TRF) is a technique by which the effects of autofluorescence are reduced by using specific fluorescent labels with long fluorescence lifetimes (compared with autofluorophores) in conjunction with time-gated detection. A time-resolved fluorescence microscope (TRFM) is described that is based on a standard epifluorescence microscope modified by the addition of a pulsed excitation source and an image-intensified time-gateable CCD camera. The choice of pulsed excitation source for TRFM has a large impact on the price and performance of the instrument. A flash lamp with rapid discharge characteristics was selected for our instrument because of the high spectral energy in the UV region and short pulse length. However, the flash output decayed with an approximate lifetime of 18 micros and the TRFM required a long-lived lanthanide chelate label to ensure that probe fluorescence was visible after decay of the flash plasma. We synthesized a recently reported fluorescent chelate (BHHCT) and conjugated it to a monoclonal antibody directed against the waterborne parasite Giardia lamblia. For a 600-nm bandpass filter set and a gate delay of 60 micros, the TRFM provided an 11.3-fold improvement in the signal-to-noise ratio (S/N) of labeled Giardia over background. A smaller gain in an SNR of 9.69-fold was achieved with a 420-nm longpass filter set; however, the final contrast ratio between labeled cyst and background was higher (11.3 versus 8.5). Despite the decay characteristics of the light pulse, flash lamps have many practical advantages compared with optical chopper wheels and modulated lasers for applications in TRFM.
Doubling the field of view in off-axis low-coherence interferometric imaging (2014)

We present a new interferometric and holographic approach, named interferometry with doubled imaging area (IDIA), with which it is possible to double the camera field of view while performing off-axis interferometric imaging, without changing the imaging parameters, such as the magnification and the resolution. This technique enables quantitative amplitude and phase imaging of wider samples without reducing the acquisition frame rate due to scanning. The method is implemented using a compact interferometric module that connects to a regular digital camera, and is useful in a wide range of applications in which neither the field of view nor the acquisition rate can be compromised. Specifically, the IDIA principle allows doubling the off-axis interferometric field of view, which might be narrower than the camera field of view due to low-coherence illumination. We demonstrate the proposed technique for scan-free quantitative optical thickness imaging of microscopic biological samples, including live neurons and a human sperm cell in rapid motion under high magnification. In addition, we used the IDIA principle to perform non-destructive profilometry during a rapid lithography process of transparent structures. Researchers in Israel have developed a method for doubling the field of view in single-exposure depth-resolved holographic imaging. Pinhas Girshovitz and Natan Shaked from Tel Aviv University based their technique on digital interferometric microscopy, which uses interference effects to extract quantitative information on the thickness or height profile of the imaged object. Such information is useful, for example, in imaging of biological samples without labeling, or for optically profiling elements for non-destructive testing with sub-nanometer accuracy. Unfortunately, to enable capturing the entire quantitative image in a single exposure, a reduction in the field of view occurs. Girshovitz and Shaked proposed a way to optically compress more information into the same camera frame without loss in the imaging details or the magnification. A compact and portable interferometric module, positioned only in the output of the imaging system, splits the image beam into two components that are then superimposed at different angles on the imaging camera. This multiplexing approach increases the information in the image and doubles the field of view over previous techniques. Therefore, they were able to image wider samples or acquire the samples in faster frame rates. The main experimental demonstrations include fast high-magnification quantitative imaging of a swimming sperm cell, and non-destructive profiling of a thin element during rapid lithography process.
Native and Mutant Forms of Cholera Toxin and Heat-Labile Enterotoxin Effectively Enhance Protective Efficacy of Live Attenuated and Heat-Killed<i>Shigella</i>Vaccines (1999)

Both native and mutant forms of cholera toxin (CT) and heat-labile enterotoxin (LT) are effective adjuvants for antigens and killed whole-cell preparations. To determine whether these toxin molecules could also boost the immunogenicity and efficacy of live attenuated vaccines directed against shigellosis, the guinea pig keratoconjunctivitis model was used to evaluate the adjuvant effect of these toxin molecules on EcSf2a-3, a DeltavirG DeltaaroD Escherichia coli-Shigella flexneri 2a hybrid vaccine strain that was previously found to be less protective than its parent strain in the guinea pig model. Experiments using native and mutant toxin molecules showed that both CT and LT and mutant derivatives were effective as an adjuvant for EcSf2a-3 and that the mutant toxin molecules, which were developed to retain adjuvanticity without the toxicity associated with the native molecules, were as effective as the native toxin molecules as adjuvants. Protective efficacy was enhanced for both the oral and intranasal routes of immunization. Serum antibody response to the S. flexneri 2a O antigen, the primary antigen for protective immunity, was not dependent on the addition of an adjuvant. However, enumeration of the O-antigen-specific immunoglobulin G (IgG) and IgA antibody-secreting cells in the spleen and draining lymph nodes following intranasal immunization suggested that enhancement of the local immune response by the toxin molecules may contribute to the observed increase in protective efficacy. The efficacy of heat-killed S. flexneri 2a was enhanced only by mutant LT molecules. These results suggest that the best candidates for enhancing the efficacy of both live attenuated and heat-killed Shigella vaccines with minimal reactogenicity are the mutant toxin molecules.
<title>Silicon naphthalocyanines derivatives: delivery systems as modulators of pharmacokinetics and photodynamic therapy (PDT) outcomes</title> (1996)

Photodynamic therapy of neoplastic tissues is a new treatment modality that combines the in- vivo administration of a photosensitizer followed by its excitation with visible light, which leads to a photochemical reaction and tissue destruction. Naphthalocyanine derivatives are a class of second-generation photosensitizers that have excellent prospects as photodynamic therapeutic agents. Relevant to these types of applications are their photochemical properties, their tumor-localizing abilities, and their ability to elicit photodynamic responses. Bis(di- isobutyloctadecylsiloxy)silicon 2,3-naphthalocyanine (isoBOSINC) illustrates some of the above promising photoproperties: absorption in the red at 776 nm with an extinction coefficient greater than 10<SUP>5</SUP> M<SUP>-1</SUP> cm<SUP>-1</SUP>, a triplet state lifetime of 331 microseconds and singlet oxygen yields of approximately 0.20. Due to their high degree of hydrophobicity, metallonaphthalocyanines require a variety of approaches before they can be administered to cells in vitro or injected in vivo. One approach is the selection of solubilizing agents or vehicles such as a solution of Tween 80 in saline or emulsions of Cremophor EL in saline. This paper describes studies in (a) drug uptake by tumors and other tissues as a function of isoBOSINC's dose; (b) drug levels in normal versus tumor-bearing rats; (c) in-vitro photostability of isoBOSINC; (d) effects of delivery systems on photosensitizer tissue levels and pharmacokinetics, and PDT outcome.
Gradient nonlinearity calibration and correction for a compact, asymmetric magnetic resonance imaging gradient system (2016)

Due to engineering limitations, the spatial encoding gradient fields in conventional magnetic resonance imaging cannot be perfectly linear and always contain higher-order, nonlinear components. If ignored during image reconstruction, gradient nonlinearity (GNL) manifests as image geometric distortion. Given an estimate of the GNL field, this distortion can be corrected to a degree proportional to the accuracy of the field estimate. The GNL of a gradient system is typically characterized using a spherical harmonic polynomial model with model coefficients obtained from electromagnetic simulation. Conventional whole-body gradient systems are symmetric in design; typically, only odd-order terms up to the 5th-order are required for GNL modeling. Recently, a high-performance, asymmetric gradient system was developed, which exhibits more complex GNL that requires higher-order terms including both odd- and even-orders for accurate modeling. This work characterizes the GNL of this system using an iterative calibration method and a fiducial phantom used in ADNI (Alzheimer's Disease Neuroimaging Initiative). The phantom was scanned at different locations inside the 26 cm diameter-spherical-volume of this gradient, and the positions of fiducials in the phantom were estimated. An iterative calibration procedure was utilized to identify the model coefficients that minimize the mean-squared-error between the true fiducial positions and the positions estimated from images corrected using these coefficients. To examine the effect of higher-order and even-order terms, this calibration was performed using spherical harmonic polynomial of different orders up to the 10th-order including even- and odd-order terms, or odd-order only. The results showed that the model coefficients of this gradient can be successfully estimated. The residual root-mean-squared-error after correction using up to the 10th-order coefficients was reduced to 0.36 mm, yielding spatial accuracy comparable to conventional whole-body gradients. The even-order terms were necessary for accurate GNL modeling. In addition, the calibrated coefficients improved image geometric accuracy compared with the simulation-based coefficients.