gebhart/patrepeval huggingface dataset:
Regulatory subunit type I‐α of protein kinase A (PRKAR1A): A tumor‐suppressor gene for sporadic thyroid cancer (2002)

The tumor-suppressor gene encoding the cyclic AMP-dependent protein kinase A type I-alpha regulatory subunit PRKAR1A has been mapped to chromosome 17 (17q22-24) and is mutated in Carney complex, a familial neoplasia syndrome that is associated with thyroid tumors. Other genes implicated in cyclic nucleotide-dependent signaling have been investigated in thyroid tumorigenesis. We studied protein kinase A (PKA) activity in noninherited follicular thyroid adenomas and follicular, papillary, and undifferentiated (anaplastic) thyroid carcinomas. We then examined these and additional thyroid tumors for losses of the 17q22-24 PRKAR1A region, mutations of the PRKAR1A gene, and expression of its peptide product. Total PKA activity was markedly increased in carcinomas over that in adenomas, whereas the ratio of free vs. total PKA activity was decreased in cancer. Consistent with these findings, the 17q22-24 region was frequently lost in cancer but not in benign adenomas. A novel inactivating mutation of the PRKAR1A gene (leading to premature termination of the predicted protein) was found in an aggressive thyroid cancer. The tumor with PRKAR1A gene mutation, as well as the tumors with 17q allelic losses, showed decreased PRKAR1A expression by immunostaining. We conclude that PRKAR1A, the most abundant regulatory subunit of protein kinase A and a principal cyclic AMP-signaling modulator, acts as a tumor-suppressor gene in sporadic thyroid cancer. Published 2002 Wiley-Liss, Inc.
Multispectral demosaicking using guided filter (2011)

Multispectral imaging is highly demanded for precise color reproduction and for various computer vision applications. Multispectral imaging with a multispectral color filter array (MCFA), which can be considered as a multispectral extension of commonly used consumer RGB cameras, could be a simple, low-cost, and practical system. A challenge of the multispectral imaging with the MCFA is multispectral demosaicking because each spectral component of the MCFA is severely undersampled. In this paper, we propose a novel multispectral demosaicking algorithm using a guided filter. The guided filter is recently proposed as an excellent structurepreserving filter. The guided filter requires so-called a guide image. A main issue of the guided filter is how to obtain an effective guide image. In our proposed algorithm, we generate the guide image from the most densely sampled spectral component in the MCFA. Then, ohter spectral components are interpolated by the guided filter. Experimental results demonstrate that our proposed algorithm outperforms other existing demosaicking algorithms both visually and quantitatively.
Abstract 4956: Pharmacological inhibition of Bruton's Tyrosine Kinase (BTK) as a therapy for insulinoma and pancreatic ductal adenocarcinoma. (2013)

Abstract Myc, a pleiotropic transcription factor that is deregulated and/or over-expressed in most human cancers, instructs multiple extracellular programs that are required to sustain the complex microenvironment needed for tumor maintenance, including remodeling of tumor stroma, angiogenesis and inflammation. We previously showed in a model of pancreatic [[Unsupported Character - Symbol Font β]] cell tumorigenesis that acute Myc activation in vivo triggers rapid recruitment of mast cells to the tumor site and that this is absolutely required for angiogenesis and macroscopic tumor expansion. Moreover, systemic inhibition of mast cell degranulation with sodium cromoglycate induced death of tumor and endothelial cells in established tumors. Hence, mast cells are required both to establish and to maintain the tumors. While this intimates that selective inhibition of mast cell function could be therapeutically efficacious, cromoglycate is not a practical drug for systemic delivery in humans and no other systemic inhibitor of mast cell degranulation has hitherto been available. Ibrutinib is a novel inhibitor of Bruton's tyrosine kinase (Btk) that blocks mast cell degranulation and is currently in clinical trials as a therapy for B cell non-Hodgkin's lymphoma. Here, we show that systemic treatment of insulinoma-bearing mice with Ibrutinib efficiently inhibits Btk, blocks mast cell degranulation and triggers collapse of tumor vasculature and tumor regression. We also show that pancreatic ductal adenocarcinoma (PDAC)-bearing mice treated with Ibrutinib survive longer and present reduced tumor stroma, suggesting that combinatorial therapy with Ibrutinib and standard of care is a feasible therapeutic approach. Conclusions: our data reinforce the notion that mast cell function is required for maintenance of certain tumor types and indicate that the Btk inhibitor Ibrutinib may be useful in treating pancreatic cancer. Citation Format: Daniel Massó-Vallés, Erika Serrano, Jonathan R. Whitfield, Joseph J. Buggy, Nicole M. Sodir, Nesrine I. Affara, Lamorna Brown Swigart, Gerard I. Evan, Laura Soucek. Pharmacological inhibition of Bruton's Tyrosine Kinase (BTK) as a therapy for insulinoma and pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4956. doi:10.1158/1538-7445.AM2013-4956
Structural alterations and inflammation in the heart after multiple trauma followed by reamed versus non-reamed femoral nailing (2020)

Multiple trauma induced cardiac structural alterations in vivo, which might contribute to the development of early myocardial damage (EMD). This study also revealed that reamed femoral nailing (reamed) is associated with more prominent immunological cardiac alterations compared to nailing without reaming (non-reamed). This suggests that the choice of the initial fracture treatment strategy might be crucial for the overall outcome as well as for any post-traumatic cardiac consequences.
Leakage Current Behavior of the Bottom Gate Poly Thin-Film Transistor Fabricated by Copper Damascene Process (2013)

Bottom-gated polycrystalline-silicon (poly-Si) thin-film transistors (TFT's) with a planarized copper (Cu) gate for large-area displays have been fabricated and characterized. The 500 nm depth of trenchs are filled up with 400 nm, 500 nm, 600 nm thickness of Cu using the damascene process of VLSI technology, poly-Si TFT's with 100 nm thick gate insulator are fabricated on the Cu gate. As the Cu gate's thickness becomes thinner, the anomalous leakage current of poly-Si TFT's is reduced significantly both before and after electrical stressing. The results simulated by 3D electric field simulator demonstrate that the structure of planarized gate in bottom-gate TFT can effectively reduce the electric field causing the field emission between the gate and the drain.
Improvement of plasma lipoprotein profiles during high-flux dialysis. (1993)

Patients undergoing maintenance hemodialysis therapy have increased mortality due to cardiovascular disease. One possible etiologic factor for this increased mortality is the lipid abnormalities associated with chronic renal failure. These include elevated triglyceride (TG) and decreased high-density lipoprotein (HDL) concentrations. Lipoprotein profiles of patients undergoing chronic hemodialysis with either saponified cellulose ester (CE) (N = 9) or polysulfone (PS) high-flux dialysis membranes (N = 10) were compared. Patients in each group received similar amounts of heparin during the dialysis. CE-dialyzed patients showed no alteration in serum TG, HDL, low-density lipoprotein, or total cholesterol when predialysis and postdialysis values were compared. PS patients, on the other hand, had a significant decrease in TG concentrations (P < 0.01) as well as a significant rise in HDL (P < 0.01). These changes might signify activation of lipoprotein lipase (LPL) during dialysis. LPL activity in PS sera was significantly greater than LPL in CE sera. Moreover, sera from PS patients inhibited LPL much less than did sera from CE patients. These findings suggest that a circulating substance not dialyzable with cellulosic membranes inhibits LPL in uremic subjects and is removed during dialysis with a PS membrane. Alternatively, the greater biocompatibility of PS may produce less LPL inhibitory cytokines during dialysis. The improvement of lipoprotein profiles in patients receiving dialysis with PS membranes may, in the long term, lead to less morbidity and mortality from atherosclerotic disease.
DNA Polymerase Alpha Subunit B Is a Binding Protein for Erlotinib Resistance in Non-Small Cell Lung Cancer (2020)

Erlotinib inhibits epithelial growth factor receptor (EGFR) kinase activity and is used to treat non-small cell lung cancer (NSCLC). Despite its high efficacy, recurrence can occur in patients who become resistant to the drug. To address the underlying mechanism of Erlotinib resistance, we investigated additional mechanisms related to mode-of-drug-action, by multiple protein-binding interactions, besides EGFR by using drug affinity responsive target stability (DARTS) and liquid chromatography-mass spectrometry (LC-MS/MS) methods with non-labeled Erlotinib. DNA polymerase alpha subunit B (POLA2) was identified as a new Erlotinib binding protein that was validated by the DARTS platform, complemented with cellular thermal shift assays. Genetic knock-down of POLA2 promoted the anti-proliferative effect of the drug in the Erlotinib-resistant cell line H1299 with high POLA2 expression, whereas the overexpression of POLA2 restored anti-proliferative effects in the Erlotinib-sensitive cell line HCC827 with low POLA2 expression. Importantly, POLA2 expression levels in four NSCLC cell lines were positively correlated with anti-proliferative Erlotinib efficacy (Pearson correlation coefficient, R = 0.9886). These results suggest that POLA2 is a novel complementary target protein of Erlotinib, and could clinically provide validity as a surrogate marker for drug resistance in patients with NSCLC.
EVALUATION FRAMEWORK FOR K-BEST SPHERE DECODERS (2010)

While Maximum-Likelihood (ML) is the optimum decoding scheme for most communication scenarios, practical implementation difficulties limit its use, especially for Multiple Input Multiple Output (MIMO) systems with a large number of transmit or receive antennas. Tree-searching type decoder structures such as Sphere decoder and K-best decoder present an interesting trade-off between complexity and performance. Many algorithmic developments and VLSI implementations have been reported in literature with widely varying performance to area and power metrics. In this semi-tutorial paper we present a holistic view of different Sphere decoding techniques and K-best decoding techniques, identifying the key algorithmic and implementation trade-offs. We establish a consistent benchmark framework to investigate and compare the delay cost, power cost, and power-delay-product cost incurred by each method. Finally, using the framework, we propose and analyze a novel architecture and compare that to other published approaches. Our goal is to explicitly elucidate the overall advantages and disadvantages of each proposed algorithms in one coherent framework.
APOBEC3A drives acquired resistance to targeted therapies in non-small cell lung cancer (2021)

Abstract Acquired drug resistance to even the most effective anti-cancer targeted therapies remains an unsolved clinical problem. Although many drivers of acquired drug resistance have been identified 1‒6 , the underlying molecular mechanisms shaping tumor evolution during treatment are incompletely understood. The extent to which therapy actively drives tumor evolution by promoting mutagenic processes 7 or simply provides the selective pressure necessary for the outgrowth of drug-resistant clones 8 remains an open question. Here, we report that lung cancer targeted therapies commonly used in the clinic induce the expression of cytidine deaminase APOBEC3A (A3A), leading to sustained mutagenesis in drug-tolerant cancer cells persisting during therapy. Induction of A3A facilitated the formation of double-strand DNA breaks (DSBs) in cycling drug-treated cells, and fully resistant clones that evolved from drug-tolerant intermediates exhibited an elevated burden of chromosomal aberrations such as copy number alterations and structural variations. Preventing therapy-induced A3A mutagenesis either by gene deletion or RNAi-mediated suppression delayed the emergence of drug resistance. Finally, we observed accumulation of A3A mutations in lung cancer patients who developed drug resistance after treatment with sequential targeted therapies. These data suggest that induction of A3A mutagenesis in response to targeted therapy treatment may facilitate the development of acquired resistance in non-small-cell lung cancer. Thus, suppressing expression or enzymatic activity of A3A may represent a potential therapeutic strategy to prevent or delay acquired resistance to lung cancer targeted therapy.
Bone‐Implant Contact on Machined and Dual Acid‐Etched Surfaces After 2 Months of Healing in the Human Maxilla (2003)

At 2 months, the mean BIC% for the dual acid-etched group increased 39.14% compared to the EBC% value, while the mean BIC% for the machined group decreased 44.70%. Based on the histomorphometric results of this study, sufficient bone for functional loading of the implant exists on a dual acid-etched surface after 2 months of healing in the posterior maxillary arch.
Polynomial-Complexity Optimal Resource Allocation Framework for Uplink SC-FDMA Systems (2011)

In this paper, we study a weighted-sum rate maximization problem in SC-FDMA which is adopted as the multiple access scheme for the uplink in the 3GPP-LTE standard. Unlike OFDMA, in addition to the restriction of allocating a sub-channel to one user at most, the multiple sub-channels allocated to a user in SC-FDMA should be consecutive as well. This renders the resource allocation problem prohibitively difficult and the standard optimization tools (e.g., Lagrange dual approach widely used for OFDMA, etc.) can not help towards its optimal solution. We propose a novel polynomial-complexity optimization framework that is inspired from the recently developed canonical duality theory. We first formulate the resource allocation problem as a binary-integer programming (BIP) problem and then transform the BIP problem into a continuous space canonical dual problem which is a concave maximization problem. Based on the solution of the continuous space dual problem, we propose a resource allocation algorithm that has polynomial complexity. We provide conditions under which the proposed algorithm is optimal. We compare the proposed algorithm with the existing algorithms in the literature to assess its performance. Simulation results show that the proposed algorithm improves the system performance significantly.
Influence of Acidic (H3PO4) and Alkaline (NaOH) Additives on the Catalytic Reductive Fractionation of Lignocellulose (2016)

Reductive catalytic fractionation of lignocellulose is a promising “lignin-first” biorefinery strategy wherein lignin is solvolytically extracted from the cell wall matrix and simultaneously disassembled, resulting in a stable lignin oil and a solid carbohydrate-rich residue. Herein, we report on the different influence of acidic (H3PO4) and alkaline (NaOH) additives on the Pd/C-catalyzed reductive processing of poplar wood in methanol (MeOH). It was found that the addition of small quantities of H3PO4 results in three rather than two product streams, since under acidic conditions both delignification and alcoholysis of hemicellulose are promoted, leaving behind a cellulose-rich pulp. The simultaneous acid-catalyzed fractionation of the carbohydrates into separate cellulose and hemicellulose streams provides opportunities for more efficient downstream conversion, as processing parameters can be tailored to the needs of both streams. Alkaline conditions, on the other hand, also enhance delignification, but additionally cause (i) the formation of lignin products other than those obtained under neutral and acidic conditions, (ii) a hampered degree of lignin depolymerization, and (iii) substantial loss of cellulose from the pulp. Further on, a modified process descriptor (LFFE: lignin first fractionation efficiency) was applied to evaluate the fractionation efficiency of lignocellulose in its three major constituents. According to this new efficiency measure, mildly acidic conditions performed best.
Identification of Catalytic Cysteine, Histidine, and Lysine Residues in Escherichia coli Homoserine Transsuccinylase (2007)

Homoserine transsuccinylase catalyzes the succinylation of homoserine in several bacterial species, the first unique step in methionine biosynthesis in these organisms. The enzyme from Escherichia coli is reported to be a dimer and uses a ping-pong catalytic mechanism involving transfer of succinate from succinyl-CoA to an enzyme nucleophile, followed by transfer to homoserine to form O-succinylhomoserine. Site-directed mutagenesis and steady-state kinetics were used to identify three amino acids that participate in catalysis. Mutation of cysteine-142 to serine or alanine eliminated all measurable activity, suggesting this amino acid acts as the catalytic nucleophile. Cysteine nucleophiles are often deprotonated by histidine residues, and histidine-235 was identified as the sole absolutely conserved histidine residue among family members. This residue was mutated to both alanine and asparagine, and no activity was observed with either mutant. Lysine-47 had been previously identified as an essential residue. Mutation of this amino acid to arginine reduced catalytic activity by greater than 90%, while mutation to alanine yielded an enzyme with <1% of wild-type activity. A pH-rate profile of the K47R mutant demonstrated that this amino acid participates in the first half reaction. The data presented here provide the first detailed description of the homoserine transsuccinylase active site and provide a framework for additional mechanistic characterization of this enzyme.
Numerically exact treatment of dissipation in a driven two-level system (2020)

Recent progress in the experimental implementations of controlled quantum systems and especially of tunable dissipation for them provides an ideal starting point for precision studies of open quantum systems and their models. However, typically the standard weak-coupling approximations are very accurate in describing the dynamics of the simplest and most easily experimentally approachable system, the qubit, since it is challenging to engineer dissipation that is strong relative to the qubit frequency while preserving a high level of control. In this paper, we propose to overcome such challenges by studying a driven qubit, for which the weak-coupling approaches may fail at dissipation rates comparable to the Rabi frequency of the drive which is typically much lower than the qubit frequency. Consequently, we observe such failure of the temporally local Lindblad master equation, the induced dynamics of which are compared with a numerically exact method. To this end, we propose a metric that may be used in experiments to verify our predictions. In addition, we study the well-known Mollow triplet and observe its meltdown owing to dissipation in an experimentally feasible parameter regime. Thus we expect our results to inspire future experimental research on open quantum systems and expand the understanding on this intriguing field of physics.
DNA in nanochannels—directly visualizing genomic information (2010)

The power of nanofluidic channels to analyze DNA is described along with practical experimental hints. As an introduction, a general overview is given on conventional DNA analysis tools, as well as tools under development towards the $1000 genome. The focus of this tutorial review is the stretching of DNA in nanoscale channels for coarse-grained mapping of DNA. To understand the behavior of the DNA, basic theory is discussed. Experimental details are revealed so that the reader, with the proper equipment, should be able to perform experiments. Basic approaches to the analysis of the data are discussed. Finally, potential future directions are discussed including the application of melting mapping as a simple barcode for the DNA.
Protein Kinase C &#950; Drives Sphingomyelin Metabolism in the Nucleus During Cell Proliferation (2013)

Nuclear sphingomyelin is mainly localized in specific lipid microdomains of the inner nuclear membrane in which the active chromatin is attached. Evidence of the presence of PKC ζ in cell nucleus, where it acts on the chromatin remodeling, phosphorylation of histones, formation of the mitotic spindle is increasing. Although the pathway of the sphingomyelin in the cells was described as target of PKC ζ or vice versa the PKC ζ as target of sphingomyelin pathway, the relationship between the two molecules in cell nucleus has not been studied. Here, the possible nuclear PKC ζ / sphingomyelin metabolism enzymes interaction was investigated during liver regeneration. We found that the phosphoPKC ζ and sphingomyelin-synthase increase during the S phase of the cell cycle, while the sphingomyelinase is activated later. The incubation of H35 hepatoma cells with D45262, a compound with 87% PKC ζ inhibitory activity at 10 microM concentration, increases specifically sphingomyelinase and inhibits sphingomyelin-synthase with the reduction of DNA and RNA synthesis as index of the delay of hepatoma cell growth. Current results indicate for the first time the presence of PKC ζ isoform in the nucleus of hepatocytes and hepatoma cells and its relationship with the sphingomyelin metabolism during the S-phase of the cell cycle. Keywords: Hepatoma cells, liver regeneration, nucleus, protein kinase C zeta, neutral-sphingomyelinase, sphingomyelin; sphingomyelin-synthase.
Audio information access from meeting rooms (2004)

We investigate approaches to accessing information from the streams of audio data that result from multi-channel recordings of meetings. The methods investigated use word-level transcriptions, and information derived from models of speaker activity and speaker turn patterns. Our experiments include spoken document retrieval for meetings, automatic structuring of meetings based on self-similarity matrices of speaker turn patterns and a simple model of speaker activity. Meeting recordings are rich in both lexical and non-lexical information; our results illustrate some novel kinds of analysis made possible by a transcribed corpus of natural meetings.
Transcriptional regulation of the lactase-phlorizin hydrolase gene by polymorphisms associated with adult-type hypolactasia (2003)

Expression of LPH mRNA in the intestinal mucosa in individuals with T(-13910) A(-22018) alleles is several times higher than that found in individuals with C(-13910), G(-22018) alleles. These findings suggest that the two SNPs, C/T(-13910) and G/A(-22018), associated with adult-type hypolactasia, are associated with the transcriptional regulation of the LPH gene. The presence of the T(-13910) A(-22018) allele also shows significant elevation of the L/S ratio.
Active control of lateral leakage in thin-ridge SOI waveguide structures (2011)

We report on the design and simulation of a novel Silicon-On-Insulator waveguide structures which when excited with TM guided light, emit TE polarized radiation with controlled radiation characteristics[1]. The structures utilize parallel leaky waveguides of specific separations. The structures are simulated using a full-vector mode-matching approach which allows visualisation of the evolution of the propagating and radiating fields over the length of the waveguide structure. It is shown that radiation can be resonantly enhanced or suppressed in different directions depending on the choice of the phase of the excitation of the waveguide components. Steps toward practical demonstration are identified.