gebhart/patrepeval huggingface dataset:
Involvement of the Paxillin Pathway in JB6 Cl41 Cell Transformation (2006)

Paxillin is a substrate of the Src tyrosine onco-kinase and is involved in cell transformation, cell spreading, migration, and cancer development mediated through the mitogen-activated protein kinase signaling cascades. Here, we showed that paxillin plays a key role in skin cell transformation induced by epidermal growth factor (EGF) or 12-O-tetradecanoylphorbol-13-acetate (TPA). To investigate the mechanism of paxillin's role in cell transformation, we established a paxillin knockdown stably transfected cell line by introducing small interfering RNA-paxillin (si-paxillin). The si-paxillin cells displayed a dramatic suppression of cell proliferation and anchorage-independent cell transformation induced by EGF or TPA compared with si-mock control cells. In si-paxillin cells, decreased activator protein-1 (AP-1)-dependent luciferase activity corresponded with suppressed AP-1 DNA binding activity. Importantly, knockdown of paxillin inhibited EGF- or TPA-induced c-Jun phosphorylation at Ser(63) and Ser(73). Furthermore, total c-Jun protein level was dramatically decreased in si-paxillin cells and was dependent on serum deprivation time. The down-regulation of c-Jun was restored in si-paxillin cells by treatment with the proteasome inhibitor lactacystin but not by the lysosome inhibitor leupeptin. These results clearly provided evidence that paxillin regulates c-Jun protein level and plays a key role in cell transformation most likely through the regulation of c-Jun stability.
Synthesis of 2‐amino‐4h‐thiazolo[5,4‐b]indole and characterization of its colored conversion products with protein tyrosine phosphatase inhibitory activity (2001)

Abstract In DMSO‐solution 2‐amino‐4 H ‐thiazolo[5,4‐ b ]indole is converted into a complex mixture of colored products. The three major conversion end‐products, of which two are inhibitors of protein tyrosine phos‐phatases (PTPs), were isolated by chromatographic methods and their structures characterized by spectro‐scopic analysis, including NMR and MS combined with computer assisted structure elucidation, and, finally, confirmed by independent chemical synthesis. Synthesis of 2‐amino‐4 H ‐thiazolo[5,4‐ b ]indole as well as its N ‐acetyl derivatives prepared from either oxindole or 2‐bromo‐1‐(2‐nitro‐phenyl)ethanone is described.
Site selective hydrogen/metal exchange: Competition and cooperation between superbases and neighboring groups (1994)

Abstract
Synthesis of (11S)- and (11R)-[11-2H1]porphobilinogen; stereochemical studies on hydroxymethylbilane synthase (PBG deaminase) (1985)

(11S)-and (11R)-[11-2H1]Porphobilinogen (PBG) are synthesized and their configurations are established by degradation to a derivative of 2H1-glycine; they are used to prove that when hydroxymethylbilane synthase (PBG deaminase) acts on PBG in the presence of ammonia, aminomethylbilane is formed with overall retention of configuration at the NH2CHD-group.
Identification of Francisella tularensis Live Vaccine Strain CuZn Superoxide Dismutase as Critical for Resistance to Extracellularly Generated Reactive Oxygen Species (2009)

Francisella tularensis is an intracellular pathogen whose survival is in part dependent on its ability to resist the microbicidal activity of host-generated reactive oxygen species (ROS) and reactive nitrogen species (RNS). In numerous bacterial pathogens, CuZn-containing superoxide dismutases (SodC) are important virulence factors, localizing to the periplasm to offer protection from host-derived superoxide radicals (O(2)(-)). In the present study, mutants of F. tularensis live vaccine strain (LVS) deficient in superoxide dismutases (SODs) were used to examine their role in defense against ROS/RNS-mediated microbicidal activity of infected macrophages. An in-frame deletion F. tularensis mutant of sodC (DeltasodC) and a F. tularensis DeltasodC mutant with attenuated Fe-superoxide dismutase (sodB) gene expression (sodB DeltasodC) were constructed and evaluated for susceptibility to ROS and RNS in gamma interferon (IFN-gamma)-activated macrophages and a mouse model of respiratory tularemia. The F. tularensis DeltasodC and sodB DeltasodC mutants showed attenuated intramacrophage survival in IFN-gamma-activated macrophages compared to the wild-type F. tularensis LVS. Transcomplementing the sodC gene in the DeltasodC mutant or inhibiting the IFN-gamma-dependent production of O(2)(-) or nitric oxide (NO) enhanced intramacrophage survival of the sod mutants. The DeltasodC and sodB DeltasodC mutants were also significantly attenuated for virulence in intranasally challenged C57BL/6 mice compared to the wild-type F. tularensis LVS. As observed for macrophages, the virulence of the DeltasodC mutant was restored in ifn-gamma(-/-), inos(-/-), and phox(-/-) mice, indicating that SodC is required for resisting host-generated ROS. To conclude, this study demonstrates that SodB and SodC act to confer protection against host-derived oxidants and contribute to intramacrophage survival and virulence of F. tularensis in mice.
Allogeneic Hematopoietic Cell Transplantation as Immunotherapy for Solid Tumors (2005)

Although myeloablative conditioning can cytoreduce or debulk malignancies, the curative antitumor effects of allogeneic hematopoietic stem cell transplantation (HCT) are mostly mediated by transplanted donor immune cells. A heightened awareness and appreciation of the immune-mediated anticancer effects that occur after allogeneic transplantation has led to the increasing use of reduced-intensity stem cell transplantation (RIST) approaches to treat advanced malignancies. The graft-versus-leukemia effects that occur against hematologic cancers after RIST have recently attracted oncologists to explore the therapeutic potential of allogeneic HCT for treatment-refractory solid tumors. Delayed tumor regression after RIST in a subset of patients with metastatic renal cell, breast, ovarian, pancreatic, and colon carcinoma has recently been reported, confirming the existence of a graft-versus-tumor effect in solid tumors. Advanced disease states, rapidly growing tumors, and accrual of patients with extremely short survival are factors that have been identified to limit the efficacy of allogeneic immunotherapy. This review discusses results of allogeneic HCT for solid tumors and the development of newer transplant strategies to optimize the potential of the graft-versus-tumor effect.
Abstract 3902: Development of Aurora A inhibitors with ortho-halophenyl substituted pyrimidines: Unusual potency, SAR and X-ray crystallography studies. (2012)

Abstract The Aurora kinases are a family of serine-threonine kinases that play an important role in the regulation of cell division. The three members of the Aurora family Aurora A, B and C share a high degree of structural homology in their kinase domain but each kinase plays a different role in the control of mitosis. Aurora A and B have received the most attention to date as anticancer targets. Detailed studies have shown Aurora A and B are over expressed in a variety of cancers and are implicated in many aspects of tumor development. Aurora A is frequently over-expressed in tumors and cancer cell lines and has characteristics of an oncogene. Aurora B is also over expressed in many cancer types but does not have oncogenic properties. Aurora B plays important roles in M phase to ensure correct chromosome-microtubule alignment and attachment and chromosomal cytokinesis. Therefore, inhibition of Aurora kinase A and B is emerging as target-based therapy in cancer treatment. From our previous work HLM-8598 was identified from an in-house chemical library as a potent and highly selective inhibitor for Aurora A (IC50 value of 0.073 ± 0.002 μM) over Aurora B (IC50 = 5.4 ± 1.8 μM). X-ray crystallography studies of HLM-8598 bound to Aurora A confirmed HLM-8598 is a type-1 kinase inhibitor that interacts with the ATP binding site of the enzyme. The HLM-8598 bound to Aurora A structure-assisted synthesis of new analogs with IC50 &amp;lt; 2.5 nM affinity. We will present the synthesis of new analogs that contain an ortho-halogen substituted phenyl moiety, structure activity relationship studies as a part of our efforts to identify unusually potent Aurora A kinase inhibitors. We will discuss the use of kinase structural elements to rationally guide compound synthesis and improve design strategy. The in vitro and in vivo activities of ortho-halogen phenyl substituted pyrimidines will be presented as unusually potent Aurora A inhibitors and potential anti-cancer agents. 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 3902. doi:1538-7445.AM2012-3902
Large color gamut displays with diffraction gratings (2016)

The ability to display a broad variety of colors has great benefits not only in the context of entertainment but also as a means to streamline design in prototyping and manufacturing processes. Displays that use RGB filters or backlights cannot span all colors that occur in nature. To improve the accuracy of color reproduction, there have been attempts to include additional color primaries in displays. Existing solutions, however, have an impact on cost, scalability, and spatial resolution and are predominantly applicable to projection systems. We propose an approach based on combining diffraction grating extractors and the HANS imaging pipeline initially developed for printing. This combination offers unprecedented potential to attain large color gamuts with the same backlights commercially used today.
Abstract 4647: Investigation of the pharmacokinetic profile of the novel PIM2 inhibitor, JP_11646 (2014)

Abstract PIM2 is a serine/threonine protein kinase that has roles in cell growth, proliferation, and apoptosis via the regulation of multiple signal transduction cascades. JP_11646 is a novel PIM2 inhibitor that has shown antitumor activity against breast, colon, liver, lung, and pancreatic solid tumors, as well as multiple myeloma and leukemia. The pharmacokinetics (PK) of JP_11646 has not been described. Therefore, a PK study was conducted to characterize JP_11646 disposition in plasma and various tissues. Normal ICR (CD-1) mice received either single day or five consecutive days of 15 - 25 mg/kg JP_11646 via intraperitoneal (IP) or intravenous (IV) administration. Plasma samples were collected at serial time points (0.5, 1, 2, 4, 6, and 8 hrs) following a single dose of 20 mg/kg IV or 25 mg/kg IP JP_11646 administration. Plasma and various tissues (brain, heart, kidney, lung, liver, muscle, colon, pancreas, and spleen) were collected at serial time points following multiple daily doses of 15 mg/kg IP JP_11646 on day five. Three mice were euthanized per time point on each collection day. JP_11646 concentrations were determined by a validated LC-MS/MS method, with a LLOQ of 1 ng/ml. Noncompartmental PK analysis was performed using Phoenix 64 (Pharsight, WinNonlin 6.3). Following single dose administration of JP_11646 of 20 (IV) and 25 mg/kg (IP), mean plasma Cmax was 6,951 and 6,630 ng/ml, respectively. Mean plasma drug exposures (AUCinf) were 11,065 and 11,024 ng-hr/ml, respectively, resulting in similar drug exposure between the IV and IP route. To compare plasma and tissue exposure following multiple dose administration, JP_11646 was given at 15 mg/kg IP. The mean plasma Cmax was 4,601 ng/ml., while the mean Cmax in colon, pancreas, and spleen were 24,523, 77,811, and 18,835 ng/ml, respectively. The half-life of JP_11646 in plasma and tissues ranged from 0.8 - 3 hrs. Tissue exposure in colon, pancreas, and spleen was 48,792, 157,273, and 40,511 ng-hr/ml, respectively. The pancreas to plasma partition coefficient (Kp) of 20.6 demonstrates that the pancreas receives the highest exposure to JP_11646. The drug also distributes to the colon and spleen, with Kp values of 6.4 and 5.3, respectively. JP_11646 PK appears linear and the half-life ranges from 0.8 - 3.0 hrs. JP_11646 distributes widely to tissues, with the highest drug exposure in the pancreas, spleen, and colon. These results give insight into tumor types with potential for optimal antitumor therapy with JP_11646. Citation Format: Laura B. Pitzonka, Allison Gaudy, Sarah Schihl, Leslie Curtin, Sandra Sexton, Carmen M. Baldino, Justin Caserta, Yvonne Flanders, Stephane Dumas, Gerald Fetterly. Investigation of the pharmacokinetic profile of the novel PIM2 inhibitor, JP_11646. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4647. doi:10.1158/1538-7445.AM2014-4647
Automatic Identification and Measurement of Cells by Computer (1969)

A visual-input computer system was used to automatically locate and perform measurements with high accuracy on single cells from microscopic slides. The nuclear radius, irregularity, area, and density of normal and malignant cells were automatically measured. These studies agreed with hand measurements showed differences normal and malignant cervical cells on Papanicolaou smears.
Correction to “A 0.5-V 74-dB SNDR 25-kHz Continuous-Time Delta-Sigma Modulator With a Return-to-Open DAC” (2007)

In the above titled paper (ibid., vol. 42, no. 3, pp. 496-507, Mar 07), corrections were made to the schematic diagram of the two-stage OTA (Figure 11).
Abstract 2750: An efficient multiplexing approach to avoid batch effects in single cell RNA- and Ab-seq studies demonstrated in a mouse model of chronic inflammation and obesity (2020)

Abstract Obesity can weaken the body's immune system and reduce its ability to fight off infections. Current analysis on immune cells from obese mouse models suggests that the immune cells suffer from chronic inflammation. To understand the root cause of this problem, we used single cell sequencing to examine thousands of immune cells isolated from primary and secondary lymphoid organs as well as adipose tissue and compared a diet-induced obesity mouse model with control mice. Cells were stained with 30 BD® AbSeq DNA-barcoded antibodies to enable multiomic analysis, i.e. examining protein alongside mRNA expression in tandem. We also utilized DNA-barcoded universal antibodies from the BD® Single-Cell Multiplexing Kit, which allowed us to combine 8 samples from different mice and tissue types into a single pooled sample, significantly reducing experimental scale and cost while eliminating potential batch effects. The pooled samples were loaded on the BD Rhapsody™ system to perform cell lysis and individual mRNA and cell barcoding, allowing measurement of ~400 immune-related mRNAs and 30 proteins at the single cell level. We were able to efficiently de-multiplex the pooled samples after sequencing. The targeted mRNA and AbSeq panel provided robust clustering of immune cell types and showed that genes related to critical immune responses, including inflammation and lymphocyte activation, are differentially regulated in specific immune-cell subsets in the obese mouse model. Using this multiomic analysis of genes differentially regulated in immune cells from different tissues, we propose a model to explain the immuno-phenotype we observed in obese mouse. For Research Use Only. Not for use in diagnostic or therapeutic procedures. BD, the BD Logo, and Rhapsody are trademarks of Becton, Dickinson and Company or its affiliates. © 2019 BD. All rights reserved. Citation Format: Hye-Won Song, Gisele Baracho, Ian Taylor, Stephanie Widmann, Stefanie Mortimer. An efficient multiplexing approach to avoid batch effects in single cell RNA- and Ab-seq studies demonstrated in a mouse model of chronic inflammation and obesity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2750.
An Edge Alignment-based Orientation Selection Method for Neutron Tomography (2022)

Neutron computed tomography (nCT) is a 3D characterization technique used to image the internal morphology or chemical composition of samples in biology and materials sciences. A typical workflow involves placing the sample in the path of a neutron beam, acquiring projection data at a predefined set of orientations, and processing the resulting data using an analytic reconstruction algorithm. Typical nCT scans require hours to days to complete and are then processed using conventional filtered back-projection (FBP), which performs poorly with sparse views or noisy data. Hence, the main methods in order to reduce overall acquisition time are the use of an improved sampling strategy combined with the use of advanced reconstruction methods such as model-based iterative reconstruction (MBIR). In this paper, we propose an adaptive orientation selection method in which an MBIR reconstruction on previously-acquired measurements is used to define an objective function on orientations that balances a data-fitting term promoting edge alignment and a regularization term promoting orientation diversity. Using simulated and experimental data, we demonstrate that our method produces high-quality reconstructions using significantly fewer total measurements than the conventional approach.
New Geometric Properties for Modelled Planar Vibration (1997)

Abstract A novel analysis is used to identify new geometric properties for a seemingly well-known model — the linear vibration of an elastically suspended rigid body in planar motion. Vibration centers describe the modes shapes and are shown to be constrained to regions specified by the center-of-elasticity, center-ofmass, and stiffness principal directions. Responses are classified by the number of pure translational modes and conditions for existence are given. Vibration centers are also applied to forced vibration problems where there is a simple relation between an applied force and the resulting mode amplitudes. Numerical examples illustrate the results.
Methods for Multiplex Template Sampling in Digital PCR Assays (2014)

The efficient use of digital PCR (dPCR) for precision copy number analysis requires high concentrations of target molecules that may be difficult or impossible to obtain from clinical samples. To solve this problem we present a strategy, called Multiplex Template Sampling (MTS), that effectively increases template concentrations by detecting multiple regions of fragmented target molecules. Three alternative assay approaches are presented for implementing MTS analysis of chromosome 21, providing a 10-fold concentration enhancement while preserving assay precision.
<title>IR technique for detection of wall thinning in service water piping</title> (1997)

The service water piping system at nuclear power plants provides cooling for a variety of safety and non-safety related components and systems. Reliability of service water piping systems is a key consideration for safe and reliable plant operations. Conventional inspection techniques for detection of pipe wall thinning usually involve the time- intensive process of ultrasonic thickness measurements, based on a grid system, of the entire pipe length. An alternative to this process may lie in the use of active infrared thermography techniques for detection of thin wall areas in the pipe. Infrared thermography (IR), in a passive mode, has been widely used by utilities for a variety of predictive maintenance applications. For assessment of service water piping, an active IR technique, thermal injection, can be used. Application of this IRNDE technique for material evaluation can provide a rapid screening technique for identification of thin wall areas in service water piping. The EPRI NDE Center participated in a preliminary evaluation of this technology at Vermont Yankee Nuclear Power Plant. Based on the promising results of the Vermont Yankee activity, the Center worked with Thermal Wave Imaging, Inc. in an effort to optimize the IR thermal injection technique for service water piping applications. A series of representative pipe mock-ups were used for evaluation. Subsequent modification of the thermal injection hardware and technique yielded more uniform thermal energy transfer, improved detection capabilities, and increased effective inspection area.
A minimum mean square error channel estimator for OFDM (1996)

A coherent decision directed detector for orthogonal frequency division multiplexing (OFDM) is proposed and analyzed. The modulator uses differential encoded signalling over a multipath frequency selective Rayleigh fading channel. The detector employs a decision directed linear minimum mean square error (LMMSE) estimator of the channel gain on each subchannel. The main idea is to explore the correlation between the subchannels in order to obtain a good channel estimate. The channel estimate is obtained by an N fft dimensional linear filter with vectors as inputs and with matrixes of size as coefficients, where N fft is the total number of carriers in the OFDM system. The proposed LMMSE based detector do not suffer from an irreducable error floor in a fading channel as a detector using differential channel estimation does.
Personalized neoantigen DNA vaccines expand tumor-specific T cells in the periphery which infiltrate the tumor in hepatocellular carcinoma. (2022)

2638 Background: Tumor neoantigens are epitopes derived from tumor-specific mutations that can be incorporated in personalized vaccines to prime T cell responses. DNA vaccines delivered with electroporation have recently shown strong CD8 and CD4 T cell responses in clinical trials. In preclinical studies, DNA-encoded neoantigen vaccines have shown induction of CD8 T cells against 50% of predicted high affinity epitopes with the ability to impact tumor growth. Methods: Paired blood and tumor biopsy samples were collected from a patient with hepatocellular carcinoma before and after treatment with GNOS-PV02 (DNA neoantigen targeted vaccine) + plasmid IL-12 + pembrolizumab. Treatment resulted in a partial response with a decrease in tumor size of 44% by RECIST (168 mm to 94 mm). TCRbeta sequencing was performed on all 4 samples and single cell TCR and transcriptome sequencing was performed from T cells isolated from the post-treatment blood sample. Newly identified TCRs in blood and tumor after vaccination were inserted into an expression vector and used to generate engineered TCR T cells. Engineered TCR T cells were tested against the neoantigens included in the vaccine and their responses characterized by flow cytometry. Results: We identified 67,893 new clones in PBMC after vaccination, 3 of which comprised between 0.1 to 1% of the total T cell clones. Moreover, we identified 5126 new clones in the tumor post vaccination, out of these, 3878 (75.68%) were not found within the patient’s pre vaccination PBMCs and 556 (10.86%) were identified within the pre vaccination PBMC pool. Importantly, of the newly identified T cells infiltrating the tumor post vaccination, we observed high frequency TCR clones of which 44 and 7 clones were above 0.1% and 1%, respectively. The majority of the newly identified T cell clones were CD8 T cells (68.75%) with an activated phenotype. Importantly, the 6 most expanded clones in blood were identified to be activated CD8+CD69+ T cells (81.82%). Engineered TCR T cells generated encoding the TCRs of these newly identified CD8 T cells showed activation when exposed to the tumor neoantigens encoded in the neoantigen DNA vaccine GNOS-PV02. Conclusions: GNOS-PV02, a neoantigen DNA vaccine, in combination with plasmid IL-12 and pembrolizumab resulted in expansion of newly identified T cells, primarily activated CD8, which trafficked to the tumor. These new tumor infiltrating T cells showed TCR specificity against tumor neoantigens encoded in GNOS-PV02 and may account for the observed objective decrease in tumor size.