gebhart/patrepeval huggingface dataset:
Abstract 4148: An orally bioavailable small molecule antagonist of TIM-3 signaling pathway shows potent anti-tumor activity (2019)

Abstract Activation of anti-tumor immune response by specific inhibition of PD1 pathway using monoclonal antibodies has now become of the mainstay in cancer therapy as evidenced by its widespread use in an expanding list of indications. Although these antibodies show impressive durable clinical activity, low response rates are witnessed in a large number of cancers, including colorectal cancer that remain largely refractory to PD-1 blockade. Upregulation of alternative immune checkpoints such as T cell immunoglobulin and mucin-domain containing-3 (TIM-3) and VISTA contributes to the lack of response in patients not responding to therapies with anti-PD-1/PD-L1 antibodies. TIM-3 is a co-inhibitory receptor expressed on IFN-γ-producing T cells, FoxP3+ Treg cells and innate immune cells. Synergistic effects in restoring the anti-tumor immunity in preclinical models upon dual blockade of TIM-3 and PD-1 has provided a strong rationale for developing TIM-3 agents for use in combination with PD1 agents in the clinic. We sought to discover and develop an orally available small molecule antagonist targeting TIM3- signaling pathways. Unlike antibodies an oral agent potentially offers the convenience, flexibility to adjust dose and schedule to address any emergent adverse events and ease of combination therapy. Because TIM-3 shares sequence and structural similarity with the B7 family ligands, a focused library of compounds mimicking the interaction of checkpoint proteins of B7 family was screened towards the functional antagonism of TIM-3. Further optimization of the hit compounds resulted in lead compounds targeting TIM-3 pathway with desirable potency and selectivity. Lead compounds exhibited potent functional activity comparable to that obtained with an anti-TIM-3 antibody in rescuing the effector functions in human PBMC-based assays. Additionally, an advanced lead compound exhibited desirable drug-like properties including solubility, metabolic stability and pharmacokinetics with good oral bioavailability. In a syngeneic tumor models, once a day oral dosing of the advanced lead compound resulted in significant tumor growth inhibition as a single agent and in combination with anti-PD1 antibody that correlated well with immune PD in the tumor. The findings reported here support the development of the oral TIM-3 antagonist for use in the clinic. Citation Format: Pottayil G. Sasikumar, Sudarshan S. Naremaddepalli, Raghuveer K. Ramachandra, Nagesh Gowda, Srinivaskumar Devarapalli, Sreenivas Adurthi, Jiju Mani, Rashmi Nair, Amit A. Dhudashiya, Dodheri S. Samiulla, Nagaraj M. Gowda, Murali Ramachandra. An orally bioavailable small molecule antagonist of TIM-3 signaling pathway shows potent anti-tumor activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4148.
QPSK Vector Signal Generation Based on Photonic Heterodyne Beating and Optical Carrier Suppression (2015)

We propose a novel scheme for quadrature phase-shift keying (QPSK) modulated vector signal generation based on photonic heterodyne beating, phase precoding, and optical carrier suppression (OCS). Different from our previous OCS-based vector signal generation schemes, in our proposed scheme, the precoded vector signal at the radio-frequency (RF) band, which is used for the drive of the intensity modulator operating at its OCS point, is generated by photonic heterodyning beating rather than a single digital-to-analog converter (DAC). Photonic heterodyne beating accomplishes the upconversion of the precoded vector signal from the baseband to the RF band, and thus, the DAC in our proposed scheme is used to generate the precoded vector signal at the baseband rather than that at the RF band, which significantly reduces the DAC bandwidth requirement. We experimentally demonstrate 17.6-GHz QPSK modulated vector signal generation based on our proposed scheme. The generated 17.6-GHz vector signal can carry up to 3-GBd QPSK data with a bit error ratio (BER) less than the hard-decision forward-error-correction (HD-FEC) threshold of $3.8\times 10^{-3}$.
The Power of Indirection: Achieving Multicast Scalability by Mapping Groups to Regional Underlays (2006)

Reliable multicast is a powerful primitive, useful for data replication, event notification (publish-subscribe), faulttolerance and other purposes. Yet many of the most interesting applications give rise to huge numbers of heavily overlapping groups, some of which may be large. Existing multicast systems scale scale poorly in one or both respects. We propose the QuickSilver Scalable Multicast protocol (QSM), a novel solution that delivers performance almost independent of the number of groups and introduces new mechanisms that scale well in the number of nodes with minimal performance and delay penalties when loss occurs. Key to the solution is a level of indirection: a mapping of groups to regions of group overlap in which communication associated with different protocols can be merged. The core of QSM is a new regional multicast protocol that offers scalability and performance benefits over a wide range of region sizes.
ChemInform Abstract: Single‐Crystal Rare‐Earth‐Doped Yttrium Orthosilicate Phosphors. (1989)

Abstract A group of new single‐crystal cathodoluminescent phosphors is obtained by bulk growth of rare‐earth‐activated Y 2 SiO 5 crystals from a melt by the Czochralski technique (dopants as Ce 3+ , Tb 3+ , Eu 3+ , Sm 3+ , Tm 3+ , Ga 3+ , and some of their combinations).
Deficiency of kinase suppressor of Ras1 prevents oncogenic ras signaling in mice. (2003)

In Drosophila and Caenorhabditis elegans, kinase suppressor of ras (KSR) positively modulates Ras/Raf-mitogen-activated protein kinase (MAPK) signaling. The precise signaling mechanism of mammalian KSR1 and its role in Ras-mediated transformation, however, remain uncertain. To gain insight into KSR1 function in vivo, we generated mice homozygous null for KSR1. ksr1-/- mice are viable and without major developmental defects. However, an unusual disorganized hair follicle phenotype manifest in epidermal growth factor receptor knockout mice is recapitulated in ksr1-/- mice, providing genetic support for the notion that epidermal growth factor receptor, Ras, and KSR1 are on the same signaling pathway in mammals. Furthermore, ksr1-/- mice allow for the definition of KSR1-dependent and -independent mechanisms of c-Raf-1 activation. In embryonic fibroblasts, epidermal growth factor and 12-O-tetradecanoylphorbol-13-acetate activated the MAPK cascade to a similar extent, yet only c-Raf-1 activation by epidermal growth factor depended on KSR1. Moreover, whereas the genesis of polyomavirus middle T antigen (MT)-driven mammary cancer appears independent of KSR1, KSR1 is obligate for v-Ha-ras-mediated skin tumor formation. The growth of MT-driven mammary tumor was moderately slowed in ksr1-/- mice, however, consistent with a decreased rate of proliferation of ksr1-/- cells (T cells and embryonic fibroblasts). Nonetheless, all ksr1-/- animals succumbed to mammary cancer. In contrast, papilloma formation in Tg.AC mice, resulting from skin-specific v-Ha-ras expression, was completely abrogated in the ksr1-/- background. Hence, MT-driven mammary tumor genesis, which is signaled through src and phosphatidylinositol 3'-kinase, appears KSR1 independent, whereas v-Ha-ras-mediated skin cancer, signaled through the Raf-1/MAPK cascade, requires KSR1. These results suggest KSR1 may represent a therapeutic target for Ras/MAPK signaling of human tumorigenesis.
Structural Health Monitoring Using Percolation Sensors—New User Cases from Operational Airliners and Chemical Plants (2013)

Materials that are prone to corrosion are normally protected from a wet environment, and this can be achieved by isolations, such as casings, coatings or seals. However, as a result of the intensive use of engineering structures, those isolations can be damaged and aqueous liquids arising from spillage, condensation or rain can enter those confined spaces. An interesting tool to detect the underlying structural damage of sealings would be offered by the detection of hidden harmful liquids by appropriate sensor networks. Percolation sensors for detecting harmful liquids can be considered as bioinspired sensors. Their specific performance is in analogy to the swelling of organic materials after the uptake of water. It is well-known that all living organisms require aqueous liquids for enabling all sorts of biological functions, and the regulation of the respective water content is therefore essential. In analogy with the interaction of water with biomaterial, the swelling of organic compounds can be used to develop a group of sensors that are proven to be useful in various SHM applications. For this purpose, different percolation sensors were developed, and since two years, three operational airliners from Lufthansa were equipped with percolation sensor networks (Boeing 737-500, 2 x Boeing 747-400) protecting the floor structure below the galley, the lavatory and the service doors areas. Moreover, a couple of percolation sensors were installed in the isolations of outdoor pipelines in chemical installations of BASF Antwerp. The results obtained are very promising in all cases, and they show that the presence of corrosive liquids is indicated in a very reliable way proving the presence of structural damage of casings, coatings and seals.
Control of ethylene synthesis by expression of a bacterial enzyme in transgenic tomato plants. (1991)

Synthesis of the phytohormone ethylene is believed to be essential for many plant developmental processes. The control of ripening in climacteric fruits and vegetables is among the best characterized of these processes. One approach to reduce ethylene synthesis in plants is metabolism of its immediate precursor, 1-aminocyclopropane-1-carboxylic acid (ACC). Soil bacteria containing an enzyme, ACC deaminase, were identified by their ability to grow on ACC as a sole nitrogen source. The gene encoding ACC deaminase was cloned and introduced into tomato plants. Reduction in ethylene synthesis in transgenic plants did not cause any apparent vegetative phenotypic abnormalities. However, fruits from these plants exhibited significant delays in ripening, and the mature fruits remained firm for at least 6 weeks longer than the nontransgenic control fruit. These results indicated that ACC deaminase is useful for examining the role of ethylene in many developmental and stress-related processes in plants as well as for extending the shelf life of fruits and vegetables whose ripening is mediated by ethylene.
Defect detection performance of the UCSD non-contact air-coupled ultrasonic guided wave inspection of rails prototype (2016)

The University of California at San Diego (UCSD), under a Federal Railroad Administration (FRA) Office of Research and Development (R&D) grant, is developing a system for high-speed and non-contact rail defect detection. A prototype using an ultrasonic air-coupled guided wave signal generation and air-coupled signal detection, paired with a real-time statistical analysis algorithm, has been realized. This system requires a specialized filtering approach based on electrical impedance matching due to the inherently poor signal-to-noise ratio of air-coupled ultrasonic measurements in rail steel. Various aspects of the prototype have been designed with the aid of numerical analyses. In particular, simulations of ultrasonic guided wave propagation in rails have been performed using a Local Interaction Simulation Approach (LISA) algorithm. The system’s operating parameters were selected based on Receiver Operating Characteristic (ROC) curves, which provide a quantitative manner to evaluate different detection performances based on the trade-off between detection rate and false positive rate. The prototype based on this technology was tested in October 2014 at the Transportation Technology Center (TTC) in Pueblo, Colorado, and again in November 2015 after incorporating changes based on lessons learned. Results from the 2015 field test are discussed in this paper.
Fire-Flame Detection Based on Fuzzy Finite Automation (2010)

This paper proposes a new fire-flame detection method using probabilistic membership function of visual features and Fuzzy Finite Automata (FFA). First, moving regions are detected by analyzing the background subtraction and candidate flame regions then identified by applying flame color models. Since flame regions generally have an irregular pattern continuously, membership functions of variance of intensity, wavelet energy and motion orientation are generate and applied to FFA. Since FFA combines the capabilities of automata with fuzzy logic, it not only provides a systemic approach to handle uncertainty in computational systems, but also can handle continuous spaces. The proposed algorithm is successfully applied to various fire videos and shows a better detection performance when compared with other methods.
Plasma dispersion effect based super-resolved imaging in silicon (2018)

We present here a new method for shaping a pulsed IR (λ = 1550nm) laser beam in silicon. The shaping is based on the plasma dispersion effect (PDE). The shaping is done by a second pulsed pump laser beam at 532nm (in either a Gaussian mode or a donut mode) which simultaneously and collinearly illuminates the silicon's surface with the IR beam. Following the PDE, and in proportion to its spatial intensity distribution, the 532nm laser beam shapes the point spread function (PSF) by controlling the lateral transmission of the IR probe beam. The use of this probe in a laser scanning microscope allows imaging and a wide range of contactless electrical measurements in silicon integrated circuits (IC) being under operation. We propose this shaping method to overcome the diffraction resolution limit in silicon microscopy on and deep under the silicon surface.
<title>Tumor-specific fluorescent contrast agents</title> (2000)

Several dyes are currently used for various biomedical applications due to their biocompatibility and high molar absorptivity. Localization of dyes in tumors may be mediated by several factors such as leaky vasculature and high metabolic activity in proliferating cells. However, these mechanisms of action make it difficult to differentiate inflammation from benign or malignant tumors. In order to enhance their tumor specificity, dyes have been conjugated to biomolecules that target unique factors in various diseased state. However, such large biomolecules can elicit adverse immunogenic reactions in humans, and are often preferentially taken up by the liver. Furthermore, for solid tumors which may rely on diffusion of the biomarkers from the vascular, penetration of large dye conjugates is not favorable. To overcome these problems, we designed and synthesized novel dye-peptide conjugates that are receptor specific. The efficacy of these new fluorescent contrast agents was tested in vivo in well-characterized rat tumor lines. The resulting optical images demonstrate that successful specific tumor targeting was achieved.
Anticancer activity of artemisinin-derived trioxanes (2006)

The recent scientific and patent literature on therapeutically promising anticancer trioxanes derived from the antimalarial artemisinin are reviewed through mid-2006. Several of these new chemical entities, especially some trioxane dimers, have selective and very potent anticancer activity even at low nanomolar concentrations. A major opportunity exists for the development of these and related trioxanes into anticancer drug candidates.
Reeb Graph Based Shape Retrieval for CAD (2003)

Our recent work has described a framework for matching solid of mechanical artifacts models based on scale-space feature decomposition. In this work we adopt a method of comparing solid models based on Multiresolutional Reeb Graphs (MRG) similarity computations. This method was originally proposed by Hilaga et al. in [1]. Reeb Graph technique applies MRG structure to comparisons of approximate models found in the graphics community, such as polygonal meshes, faceted representation and Virtual Reality Modeling Language (VRML) models. First, we provide a brief review of shape matching using Multiresolutional Reeb Graphs and present an approach to matching solid models. Second, we show the performance of the Reeb Graph technique when handling primitive CAD models, such as cubes and spheres; then we perform experiments with more complex models, such as LEGO models and mechanical parts, and we discuss Reeb Graph technique’s performance on complex CAD models. Third, we emphasize several problems with the existing technique. Finally, we conclude with discussion of future work.
fTPM: A Software-Only Implementation of a {TPM} Chip (2016)

Commodity CPU architectures, such as ARM and Intel CPUs, have started to offer trusted computing features in their CPUs aimed at displacing dedicated trusted hardware. Unfortunately, these CPU architectures raise serious challenges to building trusted systems because they omit providing secure resources outside the CPU perimeter. This paper shows how to overcome these challenges to build software systems with security guarantees similar to those of dedicated trusted hardware. We present the design and implementation of a firmware-based TPM 2.0 (fTPM) leveraging ARM TrustZone. Our fTPM is the reference implementation of a TPM 2.0 used in millions of mobile devices. We also describe a set of mechanisms needed for the fTPM that can be useful for building more sophisticated trusted applications beyond just a TPM.
Association of Promoter Methylation of VGF and PGP9.5 with Ovarian Cancer Progression (2013)

Our results indicate that VGF and PGP9.5 PH are potential biomarkers for ovarian carcinoma. Confirmatory cohorts with longitudinal follow-up are required in future studies to define the clinical impact of VGF and PGP9.5 PH before clinical application.
HOST RANGE AND INTERFERENCE STUDIES OF THREE CLASSES OF PIG ENDOGENOUS RETROVIRUS (1999)

SP-03 Recent interest in the use of porcine organs, tissues and cells for xenotransplantation to humans has highlighted the need to characterise the properties of pig endogenous retroviruses (PERVs)1-4. Analysis of a variety of pig cells allowed us to isolate and identify three classes of infectious type C endogenous retrovirus (PERV-A, -B and -C) which have distinct env genes, but share highly homologous sequences in the rest of the genome. To study the properties of these env genes, expression plasmids for the three env genes were constructed and used to generate retrovirus vectors bearing corresponding Env proteins. Host range analyses by the vector transduction assay showed that PERV-A and PERV-B Envs have wider host ranges including several human cell lines compared with PERV-C Env which infected only 2 pig cell lines and 1 human cell line. Receptors for PERV-A and PERV-B were present on cells of some other species, including mink, rat, mouse and dog, suggesting that such species may provide useful model systems to study infection and pathogenicity of PERV. In contrast, no vector transduction was observed on non-human primate cell lines, casting doubt on the utility of non-human primates as models for PERV zoonosis. Interference studies showed that the three PERV strains use distinct receptors to each other and to a number of other type C mammalian retroviruses.
Molecular Cloning and Characterization of Plastin, a Human Leukocyte Protein Expressed in Transformed Human Fibroblasts (1988)

The phosphoprotein plastin was originally identified as an abundant transformation-induced polypeptide of chemically transformed neoplastic human fibroblasts. This abundant protein is normally expressed only in leukocytes, suggesting that it may play a role in hemopoietic cell differentiation. Protein microsequencing of plastin purified from leukemic T lymphocytes by high-resolution two-dimensional gel electrophoresis produced eight internal oligopeptide sequences. An oligodeoxynucleotide probe corresponding to one of the oligopeptides was used to clone cDNAs from transformed human fibroblasts that encoded the seven other oligopeptides predicted for human plastin. Sequencing and characterization of two cloned cDNAs revealed the existence of two distinct, but closely related, isoforms of plastin--l-plastin, which is expressed in leukocytes and transformed fibroblasts, and t-plastin, which is expressed in normal cells of solid tissues and transformed fibroblasts. The leukocyte isoform l-plastin is expressed in a diverse variety of human tumor cell lines, suggesting that it may be involved in the neoplastic process of some solid human tumors.
Chemical Modification by Polyethylene Glycol of the Anti‐tumor Enzyme Arginine Deiminase from <i>Mycoplasma arginini</i> (1993)

Amino acid-degrading enzymes are known to inhibit the growth of tumor cells in culture by depleting amino acids in the medium. Here we demonstrate that arginine deiminase (EC 3.5.3.6) from Mycoplasma arginini had stronger growth-inhibitory activity against all 4 kinds of tumor cell lines tested than L-asparaginase and arginase, which are well-known anti-tumor enzymes. Next, chemical modification of the arginine deiminase molecule with polyethylene glycol was shown to enhance its potency as an anti-tumor enzyme. The percentage of modified amino groups per molecule was estimated to be 51% of the total amino groups, and the average molecular weight was estimated to be about 400,000 by gel-filtration HPLC. The enzymic activity of the modified enzyme was 25.5 units/mg protein, which was equivalent to 57% of that of the native enzyme. The modified enzyme strongly inhibited growth of a mouse hepatoma cell line, MH134, at a concentration of more than 10 ng/ml, showing almost the same dose-response curve as the native enzyme. When a bolus of 5 units of the modified enzyme was intravenously injected into male BDF1 mice, L-arginine in the blood completely disappeared within 5 min, and remained undetectable for more than 8 days. On the other hand, in the case of bolus injection of the same number of units of native enzyme, the plasma L-arginine level recovered up to 66% of the control level at 8 days. These results suggest that this modified enzyme has a longer plasma clearance time and may be more effective as a new anti-tumor agent than the native enzyme.
Raman spectroscopy for cancer detection: a review (2002)

This article reviews recent developments in the attempt to develop diagnostic techniques for cancers and precancers based on Raman spectroscopy. The article summarizes some facts about cancer biology as it pertains to Raman diagnosis. It reviews certain instrumentation considerations and finally surveys the application of Raman spectroscopy for diagnosis on intact tissues. The article concludes with our perspective on the current status of Raman spectroscopy for clinical applications and its future.