gebhart/patrepeval huggingface dataset:
Homozygous deletion of the MTAP gene in invasive adenocarcinoma of the pancreas and in periampullary cancer: A potential new target for therapy (2005)

Methylthioadenosine phosphorylase (MTAP) plays an important role in the salvage pathway for the synthesis of adenosine. Novel chemotherapeutic strategies exploiting the selective loss of MTAP function in cancers have been proposed. The MTAP gene, on chromosome 9p21, is frequently included within homozygous deletions of the p16INK4A/ CDKN2A gene. Biallelic deletions of the p16INK4A/CDKN2A gene are found in 40% of pancreatic cancers, suggesting that the MTAP gene may be frequently inactivated in pancreatic cancer and that selected patients with pancreatic cancer may benefit from therapies targeting this loss. We immunolabeled six xenografted pancreatic cancers with known MTAP and p16INK4A/CDKN2A gene status and found that immunolabeling mirrored gene status. Loss of expression of both MTAP and p16 was observed only in those pancreatic cancers with homozygous deletions that encompassed both the MTAP and p16INK4A/CDKN2A genes. We then immunolabeled a series of 320 microarrayed infiltrating pancreatic adenocarcinomas, 35 biliary adenocarcinomas, 54 ampullary cancers, and 35 noninvasive intraductal papillary mucinous neoplasms. Immunolabeling for MTAP was lost in 91 of the 300 (30%) evaluable pancreatic cancers, 9 of 54 (17%) ampullary cancers, 4 of 33 (12%) biliary cancers, and in 1 of 35 (3%) IPMNs. All neoplasms with loss of MTAP labeling also demonstrated loss of p16 labeling. These results suggest that MTAP expression is lost in approximately 30% of infiltrating pancreatic cancers and in a lower percentage of other periampullary neoplasms, that this loss is the result of homozygous deletions encompassing both the MTAP and p16INK4A/CDKN2A genes. Thus, pancreatic cancer is a promising cancer type in which to explore novel chemotherapeutic strategies to exploit the selective loss of MTAP function.
Data from Regulation of CD4<sup>+</sup>NKG2D<sup>+</sup> Th1 Cells in Patients with Metastatic Melanoma Treated with Sorafenib: Role of IL-15Rα and NKG2D Triggering (2023)

&lt;div&gt;Abstract&lt;p&gt;Beyond cancer-cell intrinsic factors, the immune status of the host has a prognostic impact on patients with cancer and influences the effects of conventional chemotherapies. Metastatic melanoma is intrinsically immunogenic, thereby facilitating the search for immune biomarkers of clinical responses to cytotoxic agents. Here, we show that a multi-tyrosine kinase inhibitor, sorafenib, upregulates interleukin (IL)-15Rα &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt; in patients with melanoma, and in conjunction with natural killer (NK) group 2D (NKG2D) ligands, contributes to the Th1 polarization and accumulation of peripheral CD4&lt;sup&gt;+&lt;/sup&gt;NKG2D&lt;sup&gt;+&lt;/sup&gt; T cells. Hence, the increase of blood CD4&lt;sup&gt;+&lt;/sup&gt;NKG2D&lt;sup&gt;+&lt;/sup&gt; T cells after two cycles of sorafenib (combined with temozolomide) was associated with prolonged survival in a prospective phase I/II trial enrolling 63 patients with metastatic melanoma who did not receive vemurafenib nor immune checkpoint–blocking antibodies. In contrast, in metastatic melanoma patients treated with classical treatment modalities, this CD4&lt;sup&gt;+&lt;/sup&gt;NKG2D&lt;sup&gt;+&lt;/sup&gt; subset failed to correlate with prognosis. These findings indicate that sorafenib may be used as an “adjuvant” molecule capable of inducing or restoring IL-15Rα/IL-15 in tumors expressing MHC class I–related chain A/B (MICA/B) and on circulating monocytes of responding patients, hereby contributing to the bioactivity of NKG2D&lt;sup&gt;+&lt;/sup&gt; Th1 cells. &lt;i&gt;Cancer Res; 74(1); 68–80. ©2013 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Abstract 1429: Bioluminescent methods for investigating metabolic pathways (2014)

Abstract Cancer cells are dependent on metabolic pathways that have been altered to support unique requirements for cancer cell growth and survival. The central role of these pathways makes them attractive targets for new treatment approaches. Rapid and sensitive assays, amenable to high-throughput screening, are needed to study the enzymes, metabolites and cofactors involved in cancer cell metabolic pathways. We developed a bioluminescent technology to address these needs and monitor changes in the fundamental metabolic co-factors nicotinamide adenine dinucleotides and key metabolites such as lactate. The bioluminescent method uses a novel proluciferin substrate for the enzyme diaphorase. Luciferin is produced in the presence of NAD(P)H, resulting in a luciferase-generated light signal proportional to the starting NAD(P)H concentration. This is a versatile technology for measuring dinucleotide concentrations, enzyme activity and also metabolite levels. When lactate dehydrogenase is included in the reaction, the cellular metabolite lactate, an indicator of glycolytic rate, can be measured. NAD, NADP, NADH and NADPH can be measured in enzyme reactions or in biological samples, such as cells and tissues, with the use of NAD- and NADP-specific cycling enzymes. Total NAD+NADH or NADP+NADPH levels in cultured cells were rapidly monitored using a one-reagent addition, in-well plate protocol without the need for cell processing. Additionally, the levels of individual dinucleotides and their ratios were determined from cell and tissue samples using a streamlined in-well acid and base-treatment protocol. The effects of small molecules on cellular dinucleotide levels can be quickly assessed, as demonstrated with FK866, an inhibitor of NAD biosynthesis. Advantages of the bioluminescent approach over other detection methods include higher sensitivity (LOD ≤ 50 nM), larger maximum signal windows (S/B &amp;gt; 100) and compatibility with automated, high-throughput protocols (Z' &amp;gt; 0.8). By providing these features, the bioluminescent assays should be useful tools for facilitating the study of cancer cell metabolic pathways and the development of therapeutics that target these pathways. Citation Format: Donna Leippe, Mary Sobol, Jolanta Vidugiriene, Wenhui Zhou, Gediminas Vidugiris, Troy Good, Laurent Bernad, Poncho Meisenheimer, James Cali. Bioluminescent methods for investigating metabolic pathways. [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 1429. doi:10.1158/1538-7445.AM2014-1429
Concurrent Intermediate Uveitis and an Enhancing Intracranial Lesion as the Initial Manifestation of Sarcoidosis (2006)

The difficulties of the initial diagnosis of sarcoidosis and the indications for initiation of steroid therapy are illustrated. We use this case to emphasise the need for a high clinical suspicion of sarcoidosis in the presence of similar unusual and seemingly unrelated combinations of neurological manifestations so as to facilitate the prompt institution of appropriate treatment when indicated.
40G-OCDMA-PON System With an Asymmetric Structure Using a Single Multi-Port and Sampled SSFBG Encoder/Decoders (2014)

In the hybrid optical code division multiple access (OCDMA) architectures using different types of optical encoder/decoder (E/Ds) between an optical line terminal and optical network units, a hybrid 40G-OCDMA-PON with a single multi-port and super-structured fiber Bragg grating (SSFBG) E/Ds is studied as a candidate system beyond next-generation PON stage 2 (NG-PON2). In this paper, we have developed uniformed and sampled SSFBG E/Ds with different refractive index profiles and have compared their code performances in a hybrid 40G-OCDMA-PON system. The experimental results show that the sampled profile improves the code dependent performances presented in many OCDMA systems. We have also demonstrated a full-duplex 4-user × 40 Gb/s hybrid OCDMA-PON system by applying the sampled SSFBG E/Ds. An asynchronous full-duplex 50 km transmission with a total capacity of 160 Gb/s (4-user × 40 Gb/s) has been achieved for the first time. Furthermore, we focus on major requirements in NG-PON2 and discuss several issues to introduce the hybrid 40G-OCDMA-PON for optical access networks.
An unexpected spontaneous Pulfrich phenomenon in amblyopia (2019)

The binocular viewing of a fronto-parallel pendulum with a reduced luminance in one eye results in the illusory tridimensional percept of the pendulum following an elliptical orbit in depth, the so-called Pulfrich phenomenon (Pulfrich, 1922). A small percentage of mild anisometropic amblyopes who have rudimentary stereo are known to experience a spontaneous Pulfrich phenomenon, which posits a delay in the cortical processing of information involving their amblyopic eye. In order to characterize this posited delay, we used a paradigm where a cylinder rotating in depth, defined by moving Gabor patches at different disparities (i.e. at different interocular phases), generates a strong to ambiguous depth percept. This paradigm allows one to accurately measure a spontaneous Pulfrich effect (i.e. PSE≠0) and to determine how it depends on the spatio-temporal properties of stimulus. We observed a spontaneous Pulfrich phenomenon in amblyopia which has been posited to be due to an interocular delay associated with amblyopic processing. Surprisingly, the posited delay was not always associated with amblyopic processing, was not a consequence of the reduced contrast sensitivity of the amblyopic eye and displayed a large variability across amblyopic observers. Increasing the density, decreasing the spatial frequency or increasing the speed of the stimulus tend to reduce the posited delay. As previously observed in controls, this delay can also be reduced or increased by a monocular manipulation of the contrast or the luminance of the stimulus. The spontaneous Pulfrich phenomenon see by some amblyopes is variable and depends on the spatio-temporal properties of the stimulus which complicates any explanation in terms of a fixed processing delay.
203. Shortened T Cell Culture with IL-7 and IL-15 Provides the Most Potent Chimeric Antigen Receptor (CAR)-Modified T Cells for Adoptive Immunotherapy (2016)

Adoptive T cell immunotherapy involves the isolation, ex vivo expansion and reinfusion of patient T cells. The efficacy of adoptive immunotherapy is dependent on the ability of T cells to engraft, expand and persist upon adoptive transfer. In this therapy, T cells are cultured ex vivo using natural or artificial antigen presenting cells that deliver signal 1 (TCR/CD3) and signal 2 (e.g. CD28 co-stimulation) along with exogenously added cytokines. IL-2 is the most commonly used cytokine for ex vivo T cell culture; however, there is renewed interest in IL-7 and IL-15 due to their ability to enhance the survival and proliferation of stem cell memory (Tscm) and central memory (Tcm) T cells. We show that primary human T cells freshly isolated from peripheral blood are heterogeneous with substantial numbers of Tscm and Tcm cells in addition to effector differentiated T cells. During ex vivo culture, these cells progressively differentiate into a population of T cells with a predominantly CD45RO+, CD27-, CCR7- effector differentiated phenotype. Exogenous IL-7 and IL-15 delay this transition in T cell phenotype and preserve a greater proportion of Tscm and Tcm cells in the final ex vivo culture product. We hypothesize that limited ex vivo culture of T cells in the presence of IL-7 and IL-15 rather than IL-2 will enhance engraftment and persistence of T cells in vivo contributing to enhanced efficacy in adoptive transfer. We show that T cells can be harvested and viably frozen from ex vivo cultures as early as day 3 following activation. Early activated T cells expressing a chimeric antigen receptor targeting CD19 (CART-19) show potent yet specific cytotoxicity and cytokine production in vitro. We investigated the therapeutic potential of cells harvested at day 3 versus later time points using a Nalm-6 leukemic cell xenograft mouse model. We demonstrate that day 3 CART-19 cells show potent anti-leukemic activity compared to day 5 or day 9 cells. Comparing CART19 cells cultured in either IL-2 or IL-7/15, we show that mice treated at a 10-fold lower dose with day 3 cells cultured in IL-7/15 exhibit the greatest anti-leukemic efficacy compared with day 9 cells where the latter fail to control leukemia. In summary, we show that limiting T cell culture ex vivo to the minimum required for lentiviral transduction in the presence of IL-7 and IL-15 provides the most efficacious T cells for adoptive T cell immunotherapy.
Deposits in Gasoline Engines - A Literature Review (1990)

&lt;div class="htmlview paragraph"&gt;This paper reviews the literature on deposits that form on all internal surfaces coming into contact with the fuel in a gasoline engine. It does not consider deposits that can form in areas primarily affected by the engine lubricant. The physical, and especially the chemical, mechanisms that lead to deposit formation are very complex and poorly understood, and are different in different parts of the engine. Deposits can impair engine operation in terms of fuel economy, power emissions, octane requirement and driveability. In the worst cases they could lead to engine damage. Deposits in most parts of the engine can be controlled through the use of fuel additives. Test procedures used in deposit-related studies are characterised by poor repeatability and reproducibility because of the complex nature of the processes involved. Deposit formation and, consequently, the effectiveness of deposit control additives also depend on base fuel properties and engine design and operation.&lt;/div&gt;
Accounting for forecast uncertainty in the optimized operation of energy storage (2016)

This paper presents and empirically evaluates two approaches to accounting for forecast uncertainty when attempting to optimize the operation of a residential battery energy storage system. Data-driven methods are used for forecasting, and dynamic programming, within a receding horizon controller, is used for operational optimization. The first method applies a discount factor to costs incurred at later intervals in a deterministic dynamic programming control horizon, provided with point forecasts. In the second approach probabilistic (scenario) forecasts are generated using Lloyd-Max quantization of the distribution of forecast errors, to allow the use of a stochastic dynamic programming formulation. These methods are applied to maximizing the cost-savings delivered from a residentially owned and operated battery, using a case-study of residential consumers with roof-top PV systems in New South Wales, Australia. It is found that scenario forecasts can offer an 8% increase in annual cost-savings, on average, when using a univariate multiple linear regression forecast.
Abstract 4924: Gene network inference models reveal novel key mediators of mammary tumorigenesis (2011)

Abstract Cancer is a developmental disease, requiring the concerted switching of multiple cellular gene programs. Here we ask whether we can use computational network inference models in a systems biology-driven approach to identify changes in connectivity within the underlying gene regulatory network during cancer progression, as well as novel key mediator genes that are central to altered disease state networks. To investigate this hypothesis, we reverse engineered the gene regulatory networks of mammary glands within normal mice and transgenic C3(1)-SV40Tag mice that undergo mammary gland transformation and tumor progression. RNA was isolated from the mammary glands of transgenic mice at 8, 12, 16 and 20 weeks of age; wild type mice were analyzed at 8 weeks. Whole genome microarray profiles were obtained for each stage. A network inference algorithm was trained on a set of 3000 genome-wide gene expression signatures from public databases. A Mode-of-action Network Inference (MNI) algorithm was used to identify key mediator genes at each stage of the gene regulatory network during different stages of cancer progression in the transgenic mouse mammary gland based on z-score significance. From this initial set of candidates, we focused on key mediator genes classified by gene ontology analysis as transcription factors. To experimentally assess the functional relevance of genes identified by this computational approach, key mediator genes were silenced in vitro in three-dimensional (3D) cultures of mouse mammary tumor epithelial cells derived from the transgenic animals. In contrast to normal mammary epithelial cells, tumor cells failed to form polarized structures containing a lumen in 3D spheroid culture. Importantly, siRNA knockdown of key mediator genes induced these cancer cells to revert to a normalized phenotype in 3D culture. These data demonstrate the feasibility of using genome reverse engineering approaches to identify genes that can potentially induce cancer reversal. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4924. doi:10.1158/1538-7445.AM2011-4924
Characterization of terahertz emission from a dc-biased filament in air (2009)

We demonstrate that the terahertz emission from a dc-biased filament can be regarded as a sum of an elliptically polarized terahertz source (generated by a filament without external electric field) and a linearly polarized terahertz source induced by the external electric field applied to the filament. The peak frequency and linewidth of the linearly polarized terahertz source are related to the average plasma density of the filament.
Imaging and Pathology Correlations for Different Risk Stratification Models for Intermediate-risk Prostate Cancer (2017)

Both models demonstrated a correlation with higher MTD for unfavorable IR patients. This is likely a driver of worse clinical outcomes.
EVERSHED EFFECT IN SUNSPOTS. (1968)

Although nevirapine plasma concentrations were 3.3 mg/l lower when co-administered with rifampin, still more than 86% of these patients had nevirapine plasma concentrations > 3.1 mg/l. Our results suggest that from a pharmacological point of view the majority of Thai coinfected patients, who have low BMIs, reach nevirapine plasma concentrations that are adequate for treatment of HIV. However this can only be undertaken if nevirapine plasma concentration monitoring is available and can be closely followed.
Representation and Evolution of Knowledge Structures to Detect Anomalies in Financial Statements (2020)

Deep learning, has delivered a variety of practical uses in the past decade. It has revolutionized customer experience and machine translation. It has made language recognition, autonomous vehicles and computer vision a reality. A multitude of other AI applications are common now. With Deep Learning we gain insights about hidden correlations. We extract features and distinguish categories. But we lack transparency of reasoning behind these conclusions. Most importantly, there is the absence of common sense. Deep learning models might be the best at perceiving patterns. Yet they cannot comprehend what the patterns mean. And they lack the ability to model their behaviors and reason about them.We present a new approach to augment Deep Learning using model based Deep Reasoning and its application to address fraud detection using financial statements. Recent theoretical models of computing structures with cognizing agents go beyond neural networks to provide models of observations, abstractions and generalizations from experience and create time dependent evolution and history to provide reasoning and predictive. We use Knowledge Structures defined therein to represent relevant domain knowledge. In this case, in a company's financial statements. We analyze their history to detect potential fraud based on specific rules and observations. We use information from governance and compliance rules and experience of past violations. We analyze SEC 10-K statements using Deep Learning and model based Deep Reasoning. We use the Knowledge Structures to identify red flags and anomalies.
Power Scaling of a 78 MHz-Repetition Rate Femtosecond Enhancement Cavity (2010)

We report on the cavity enhancement of a 78MHz, 200fs ytterbium-fiber laser system. Constant enhancement up to a record intra-cavity average power of 18kW has been observed. Beyond the linear regime, 40kW have been achieved.
Complexation of Lanthanides(III), Americium(III), and Uranium(VI) with Bitopic N,O Ligands: an Experimental and Theoretical Study (2011)

New functionalized terpyridine-diamide ligands were recently developed for the group actinide separation by solvent extraction. In order to acquire a better understanding of their coordination mode in solution, protonation and complexation of lanthanides(III), americium(III), and uranium(VI) with these bitopic N,O-bearing ligands were studied in homogeneous methanol/water conditions by experimental and theoretical approaches. UV-visible spectrophotometry was used to determine the protonation and stability constants of te-tpyda and dedp-tpyda. The conformations of free and protonated forms of te-tpyda were investigated using NMR and theoretical calculations. The introduction of amide functional groups on the terpyridine moiety improved the extracting properties of these new ligands by lowering their basicity and enhancing the stability of the corresponding 1:1 complexes with lanthanides(III). Coordination of these ligands was studied by density functional theory and molecular dynamics calculations, especially to evaluate potential participation of hard oxygen and soft nitrogen atoms in actinide coordination and to correlate with their affinity and selectivity. Two predominant inner-sphere coordination modes were found from the calculations: one mode where the cation is coordinated by the nitrogen atoms of the cavity and by the amide oxygen atoms and the other mode where the cation is only coordinated by the two amide oxygen atoms and by solvent molecules. Further simulations and analysis of UV-visible spectra using both coordination modes indicate that inner-sphere coordination with direct complexation of the three nitrogen and two oxygen atoms to the cation leads to the most likely species in a methanol/water solution.
Multiple-Stage Mass Spectrometry (2016)

This document contains recommendations for terminology in mass spectrometry. Development of standard terms dates back to 1974 when the IUPAC Commission on Analytical Nomenclature issued recommendations on mass spectrometry terms and definitions. In 1978, the IUPAC Commission on Molecular Structure and Spectroscopy updated and extended the recommendations and made further recommendations regarding symbols, acronyms, and abbreviations. The IUPAC Physical Chemistry Division Commission on Molecular Structure and Spectroscopy’s Subcommittee on Mass Spectroscopy revised the recommended terms in 1991 and appended terms relating to vacuum technology. Some additional terms related to tandem mass spectrometry were added in 1993 and accelerator mass spectrometry in 1994. Owing to the rapid expansion of the field in the intervening years, particularly in mass spectrometry of biomolecules, a further revision of the recommendations has become necessary. This document contains a comprehensive revision of mass spectrometry terminology that represents the current consensus of the mass spectrometry community.