gebhart/patrepeval huggingface dataset:
Opposing Effects of Inhibitors of Aurora-A and EGFR in Autosomal-Dominant Polycystic Kidney Disease (2015)

Aurora-A kinase (AURKA) overexpression in numerous tumors induces aneuploidy, in part because of cytokinetic defects. Alisertib and other small-molecule inhibitors targeting AURKA are effective in some patients as monotherapies or combination therapies. Epidermal growth factor receptor (EGFR) pro-proliferative signaling activity is commonly elevated in cancer, and the EGFR inhibitor erlotinib is commonly used as a standard of care agent for cancer. An erlotinib/alisertib combination therapy is currently under assessment in clinical trials, following pre-clinical studies that indicated synergy of these drugs in cancer. We were interested in further exploring the activity of this drug combination. Beyond well-established functions for AURKA in mitotic progression, additional non-mitotic AURKA functions include control of ciliary stability and calcium signaling. Interestingly, alisertib exacerbates the disease phenotype in mouse models for autosomal-dominant polycystic kidney disease (ADPKD), a common inherited syndrome induced by aberrant signaling from PKD1 and PKD2, cilia-localized proteins that have calcium channel activity. EGFR is also more active in ADPKD, making erlotinib also of potential interest in this disease setting. In this study, we have explored the interaction of alisertib and erlotinib in an ADPKD model. These experiments indicated erlotinib--restrained cystogenesis, opposing alisertib action. Erlotinib also interacted with alisertib to regulate proliferative signaling proteins, albeit in a complicated manner. Results suggest a nuanced role of AURKA signaling in different pathogenic conditions and inform the clinical use of AURKA inhibitors in cancer patients with comorbidities.
Influence of cholesterol on the structural preferences of dioleoylphosphatidylethanolamine-dioleoylphosphatidylcholine systems: a phosphorus-31 and deuterium nuclear magnetic resonance study (1982)

The polymorphic phase behavior of mixtures of synthetic dioleoylphosphatidylethanolamine (DOPE) and dioleoylphosphatidylcholine (DOPC) and the influence of cholesterol on these phase preferences have been investigated by employing nuclear magnetic resonance (NMR) techniques. In particular, 31P NMR procedures are utilized to study the overall phase preferences of these mixed systems, whereas 2H NMR is employed to monitor the structural preferences of individual components of these systems by using versions of DOPE and DOPC which are deuterium (2H) labeled at the C11 position of the acyl chains. The results obtained show that DOPE-DOPC systems containing as little as 20 mol % DOPC initially assume lamellar structure at 40 degrees C, even though DOPE in isolation prefers the hexagonal (HII) organization at this temperature. However, this lamellar organization appears to represent a metastable state, as incubation for extended periods at 40 degrees C results in formation of a structure, possibly the cubic phase, in which the phospholipids experience isotropic motional averaging. The addition of cholesterol induces hexagonal (HII) phase organization. 2H NMR studies of appropriately labeled versions of these systems indicate that cholesterol does not produce such effects by associating preferentially with either DOPE or DOPC. Further, in situations where bilayer, hexagonal, or "isotropic" phases coexist in the same sample, the phospholipids exhibit apparently ideal mixing behavior.
A New Catalyzed Hydrocarbon Trap Control System for ULEV/SULEV Standard (2003)

&lt;div class="htmlview paragraph"&gt;A new catalyzed hydrocarbon (HC) trap control system has been developed to reduce HC emission at cold engine start. The HC trap function changes according to its temperature, so it is important to optimize its temperature profile. To realize the best profile, the engine system was optimized with a thin wall exhaust tube, a thin wall HC trap and a new engine control, which controls ignition timing without engine stability deterioration. In a LA-4 mode test with some trial HC traps, the results showed good performance which met ULEV/SULEV standard.&lt;/div&gt;
Absence of Substrate Channeling between Active Sites in the Agrobacterium tumefaciens IspDF and IspE Enzymes of the Methyl Erythritol Phosphate Pathway (2006)

The conversion of 2-C-methyl-d-erythritol 4-phosphate (MEP) to 2-C-methyl-d-erythritol 2,4-cyclodiphosphate (cMEDP) in the MEP entry into the isoprenoid biosynthetic pathway occurs in three consecutive steps catalyzed by the IspD, IspE, and IspF enzymes, respectively. In Agrobacterium tumefaciens the ispD and ispF genes are fused to encode a bifunctional enzyme that catalyzes the first (synthesis of 4-diphosphocytidyl-2-C-methyl d-erythritol) and third (synthesis of 2-C-methyl-d-erythritol 2,4-cyclodiphosphate) steps. Sedimentation velocity experiments indicate that the bifunctional IspDF enzyme and the IspE protein associate in solution, raising the possibility of substrate channeling among the active sites in these two proteins. Kinetic evidence for substrate channeling was sought by measuring the time courses for product formation during incubations of MEP, CTP, and ATP with the IspDF and IspE proteins with and without an excess of the inactive IspE(D152A) mutant in the presence or absence of 30% (v/v) glycerol. The time dependencies indicate that the enzyme-generated intermediates are not transferred from the IspD active site in IspDF to the active site of IspE or from the active site in IspE to the active site of the IspF module of IspDF.
Efficiency improvement of InGaN LEDs at elevated temperature with dome-shaped patterned-sapphire substrates (2021)

The efficiency of InGaN LEDs working at elevated temperatures has been improved by introducing patterned-sapphire substrates with dome-shaped nanostructures of the optimized height through the analysis of electroluminescence of devices using an integrating sphere.
Estimation of deflections by interferometry in a cantilever array and its optimization based on a two-scale model (2013)

In this paper, our attention is focused on a two-scale model based algorithm for deflection estimation of array of Atomic force microscopes (AFM) in quasi-static regime by interferometry. In a previous work, an algorithm based on three measurements by cantilever was introduced to compute their displacements in quasi-static regime. Here, we propose an improvement so that two measurements only are required. This is based on a published two-scale model of such array. Numerical simulation results of topographic scan by an array of AFMs on a sample surface are reported. The simulations are carried out with a model calibrated from a device which design optimization is also discussed here.
Measurement of the forward Z boson production cross-section in pp collisions at s = 7 $$ \sqrt{s}=7 $$ TeV (2015)

A measurement of the production cross-section for Z bosons that decay to muons is presented. The data were recorded by the LHCb detector during pp collisions at a centre-of-mass energy of 7 TeV, and correspond to an integrated luminosity of 1.0 fb -1 . The cross-section is measured for muons in the pseudorapidity range 2.0 < < 4.5 with transverse momenta p T > 20 GeV/c. The dimuon mass is restricted to 60 < M + -< 120 GeV/c 2 . The measured cross-section is
On the effects of Gaussian channel estimation errors on the capacity of adaptive transmission with space-time block coding (2006)

In this paper, we derive general closed-form expressions for the Shannon capacity achieved by orthogonal space-time block coding (STBC) over Rayleigh fading channels under adaptive transmission and channel estimation errors. Adaptive transmission can be performed on a frame-by-frame basis provided that a channel state information (CSI), consisting of the SNR level as estimated by the receiver, is fed back to the transmitter, thereby allowing for different compromises between the achievable capacity and the corresponding implementation complexity. The closed-form capacity formulae, derived for different power and rate allocation policies, are expressed in terms of the number of transmit and receive antennas, the code-rate of the STBC mapping, the average SNR per receive antenna, and a single parameter capturing Gaussian channel estimation errors. Numerical results showing the effects of the estimation errors on the capacity of STBC subject to the adaptive transmission policies under consideration are provided.
A Two-Stage Tremor Detection Algorithm for Wearable Inertial Sensors During Normal Daily Activities (2019)

Continuous monitoring of tremor with wearable wrist sensors during normal daily activities is more difficult than in a clinical setting when subjects perform prescribed activities because some normal daily activities resemble tremor, many normal movements contain frequency content that overlaps with the tremor frequency, and the tremor amplitude has a large dynamic range during normal daily activities. We describe a novel two-stage algorithm that offers improvement at discriminating tremor from other activities. Some of this improvement is attained by using prior domain knowledge that tremor occurs over a narrow range of frequencies for an individual, but the mean tremor frequency may vary significantly between individuals in a study population. We validated the algorithm in continuous recordings from people with Parkinson's disease and matched control subjects. The algorithm has good face validity, a low rate of false positives on recordings from control subjects (<; 1.1%), and good correspondence with the constancy of rest tremor as measured by this question on the MDS-UPDRS (ρ = 0.54).
Application of parallel processing to PWR plant predictive simulator. (1990)

A parallelism analysis integrated system (PARIS) with an MIMD multiprocessor scheme has been developed to analyze a simulation program which can execute anomaly effect prediction in nuclear power plants and to make the simulation program for parallel processing. The PARIS system analyzes task parallelism and processing time of each task when a user divides a program developed for a single processor into many tasks that are the elementary assignment units. Next, this system assigns tasks to processors using the static scheduling algorithm CP/ MISF to minimize the overall processing time, and makes a parallel execution program which can be executed with a tightly coupled multiprocessor.
Modeling bacterial UDP-HexNAc: polyprenol-P HexNAc-1-P transferases (2005)

Protein N-glycosylation in eukaryotes and peptidoglycan biosynthesis in bacteria are both initiated by the transfer of a D-N-acetylhexosamine 1-phosphate to a membrane-bound polyprenol phosphate. These reactions are catalyzed by a family of transmembrane proteins known as the UDP-D-N-acetylhexosamine: polyprenol phosphate D-N-acetylhexosamine 1-phosphate transferases. The sole eukaryotic member of this family, the d-N-acetylglucosamine 1-phosphate transferase (GPT), is specific for UDP-GlcNAc as the donor substrate and uses dolichol phosphate as the membrane-bound acceptor. The bacterial translocases, MraY, WecA, and WbpL, utilize undecaprenol phosphate as the acceptor substrate, but differ in their specificity for the UDP-sugar donor substrate. The structural basis of this sugar nucleotide specificity is uncertain. However, potential carbohydrate recognition (CR) domains have been identified within the C-terminal cytoplasmic loops of MraY, WecA, and WbpL that are highly conserved in family members with the same UDP-N-acetylhexosamine specificity. This review focuses on the catalytic mechanism and substrate specificity of these bacterial UDP-D-N-acetylhexosamine: polyprenol phosphate D-N-acetylhexosamine 1-P transferases and may provide insights for the development of selective inhibitors of cell wall biosynthesis.
AN ALL-OPTICAL HOPFIELD NETWORK: THEORY AND EXPERIMENT (1991)

The implementation of an all-optical Hopfield-type neural network is made possible by eliminating the need for subtracting light intensities. This implementation is achieved without significantly degrading the network's performance, when only inhibitory connections (i.e., J ij &lt;0) are used. The theoretical analysis of such a network, and its experimental implementation, exploiting a liquid crystal light valve for the neurons and an array of subholograms for the interconnections, are presented.
Tubulin and FtsZ structures: functional and therapeutic implications (1998)

The microtubule cytoskeleton has lagged nearly a decade behind the actin cytoskeleton with respect to structural information on the basic polymer subunit. This structural inferiority complex has finally been lifted by two recent papers describing the structures of the alpha beta tubulin dimer and FtsZ, a protein similar to tubulin that is essential for cell division in prokaryotes.
Application of a Homogenous Assay for the Detection of 2,4,6-Trinitrotoluene to Environmental Water Samples (2005)

A homogeneous assay was used to detect 2,4,6-trinitrotoluene (TNT) spiked into environmental water samples. This assay is based on changes in fluorescence emission intensity when TNT competitively displaces a fluorescently labeled, TNT analog bound to an anti-TNT antibody. The effectiveness of the assay was highly dependent on the source of the sample being tested. As no correlation between pH and assay performance was observed, ionic strength was assumed to be the reason for variation in assay results. Addition of 10 phosphate-buffered saline to samples to increase their ionic strength to that of our standard laboratory buffer (about 0.17 M) significantly improved the range over which the assay functioned in several river water samples.
Perception Based Hardcopy Banding Metric (2005)

Printer banding artifacts have been studied and analyzed by many researchers. However, banding reduction still remains an important image quality topic in the printing industry. A knowledge of how banding is perceived by human observers is vital information in designing improved new products.In this paper we develop an analytical tool for modeling perceived banding based on human perception. We describe new Crossplatform experiments using 10 different laser printers having different imaging characteristics, and we analyze banding of the ten printers with line screen patterns. We employ pulse width modulation capability to match the absorptance of the printers, and to also generate extrinsic banding signals.The experimental results identify the points of subjective equality of the ten printers relative to the banding of a reference printer, and provide the basis of a method of computing banding power by considering a contrast sensitivity function. Our results show that regardless of different banding spectral characteristics, the contrast banding power of a given printer can be mapped to the contrast banding power of one reference printer with added extrinsic banding. This implies that using our technique, we can reliably estimate the perceived amount of banding in a printer.
Acceleration of Spectral Domain Immitance Approach for Generalized Multilayered Shielded Microstrips Using the Levin’s Transformation (2014)

This letter reports on the acceleration of the infinite series summation in the multilayered shielded microstrip with multiple strips by using the spectral domain immitance approach (SDIA) and the Levin's transformation. This technique does not need the asymptotic expansion for the Green's functions and the basis functions by recasting the matrix elements into the form that is evaluated by the Levin's transformation. It greatly saves the work for finding the asymptotic expansion coefficients. Using only the first leading term extraction, the overall acceleration performance is further improved. Convergence properties of SDIA by using this method match with or are even better than other acceleration techniques with high order leading term extraction.
SQL, the complete reference (1999)

From the Publisher:
SQL: The Complete Reference provides an in-depth discussion of SQL fundamentals, modern SQL products, and SQLs role in trends such as data warehousing, thinclient architectures, and Internet-based e-commerce. This book is your one-stop resource for all you need to know about SQL.
Abstract 3712: The C-terminal HSP90 inhibitor, a novel deguelin derivative, exerts anti-metastatic effects in triple-negative breast cancer by targeting cancer stem-like properties (2022)

Abstract Purpose: Triple-negative breast cancer (TNBC) still relies on non-selective cytotoxic anticancer agents due to the absence of established molecular targets for the phenotype. The heat shock protein 90 (HSP90) is a promising therapeutic target because it affects the overall progression of cancer, including cell proliferation, angiogenesis and metastasis. A variety of N-terminal HSP90 inhibitors have been tried several times in clinical trials, but none have been approved for clinical use to date due to issues including heat shock response (HSR) induction, undesirable effects, and clinical toxicity. In this study, we sought to investigate whether a novel C-terminal HSP90 inhibitor SL-145 could resolve metastasis in TNBC through inhibition of cancer stem-like properties. Experimental Design: The effects of SL-145 on TNBC cell lines in vitro were evaluated in terms of cell proliferation, apoptosis, caspase-3 activity, breast cancer stem cell (BCSC)-like properties and heat shock response. An orthotopic allograft model with 4T1 mammospheres was used to examine the effect of SL-145 on tumor growth and metastasis in vivo. Results: SL-145 induces apoptosis without triggering the HSR and simultaneously inhibits several oncogenic signaling pathways including AKT, MEK/ERK and JAK2/STAT3. SL-145 effectively targets BCSC-like properties with significant reductions in CD44, CD49f and ALDH1 expression as well as impairment of mammosphere-forming ability. To confirm the physiological relevance of our in vitro observations, we investigated the effects of SL-145 on tumor growth, angiogenesis and metastasis in mammosphere-derived allograft tumors with self-renewal capacity. SL-145 administration reduced tumor burden and angiogenesis, which were enriched in BCSCs, and it resulted in significant reductions in lung and liver metastases. In addition, no toxic effects of inhibitors on markers of liver or renal function were observed. Conclusion: Our findings suggest that SL-145 may represent an effective therapeutic approach for targeting cancer stem cells and simultaneous inhibition of the HSP90 client oncoprotein to treat TNBC with a heterogeneous and aggressive nature. Citation Format: Minsu Park, Tae-Min Cho, Soeun Park, Jung Min Park, Juyeon Seo, Dongmi Ko, Seongjae Kim, So Ra Seuk, Yong Gu Kang, Kee Dal Nam, Yoon-Jae Kim, Ji Young Kim, Jae Hong Seo. The C-terminal HSP90 inhibitor, a novel deguelin derivative, exerts anti-metastatic effects in triple-negative breast cancer by targeting cancer stem-like properties [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3712.
Abstract P3-03-01: Double PIK3CA mutations in cis drive oncogene addiction and enhance sensitivity to PI3K alpha inhibitors in breast cancer (2020)

Abstract Activating mutations in PIK3CA, the gene coding for the catalytic subunit (p110α) of phosphoinositide-3-kinase (PI3K), are the most frequent oncogenic alterations in estrogen receptor-positive (ER+) breast cancer and are also prevalent in other tumor types. PI3Kα inhibitors including alpelisib have recently been shown to be clinically active in ER+ PIK3CA mutant breast cancer. To characterize determinants of sensitivity to these agents, we undertook a comprehensive analysis of PIK3CA mutant cancer genomes and observed the presence of double PIK3CA mutations in 12-15% of breast cancer and other tumor types. These double PIK3CA mutations are clonal, located in cis on the same allele, and are composed of a single hotspot mutation combined with a recurrent second-site mutation. Double PIK3CA mutations in cis result in increased PI3K activity and downstream signaling together with enhanced cell proliferation and tumor growth compared to single hotspot mutations. The biochemical mechanisms underlying this increased oncogenicity include increased disruption of p110α binding to the inhibitory subunit p85α, which relieves its catalytic inhibition, and increased membrane lipid binding. Finally, these double PIK3CA mutations predict for increased sensitivity to PI3Kα inhibitors compared to single hotspot mutations (e.g. E545K or H1047R) in experimental models and in patients with ER+ PIK3CA mutant metastatic breast cancer from the SANDPIPER randomized phase III clinical trial. These findings implicate double PIK3CA mutations in cis as a novel mechanism of oncogene addiction relative to single hotspot mutations, providing a rationale to develop PI3Kα inhibitors for the therapy of double PIK3CA mutant cancers. Citation Format: Neil Vasan, Pedram Razavi, Jared L Johnson, Hong Shao, Timothy Wilson, Frauke Schimmoller, Hardik Shah, Alesia Antoine, Erik Ladewig, Alexander Gorelick, Ting-Yu Lin, Eneda Toska, Guotai Xu, Abiha Kazmi, Matthew T Chang, Barry S. Taylor, Maura N. Dickler, Komal Jhaveri, Sarat Chandarlapaty, Raul Rabadan, Ed Reznik, Melissa L Smith, Robert Sebra, Lori Friedman, Lewis C Cantley, Maurizio Scaltriti, José Baselga. Double PIK3CA mutations in cis drive oncogene addiction and enhance sensitivity to PI3K alpha inhibitors in breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-03-01.
Supplementary Figure S7 from Adiponectin Receptor Signaling on Dendritic Cells Blunts Antitumor Immunity (2023)

&lt;p&gt;Over-expression of AdipoR1/R2 promotes T cell anergy at physiological level of APN.&lt;/p&gt;
Transcriptomic and proteomic regulation through abundant, dynamic, and independent arginine methylation by Type I and Type II PRMTs (2020)

Abstract Arginine methylation is essential for both cellular viability and development and is also dysregulated in cancer. PRMTs catalyze the post translational monomethylation (Rme1/MMA, catalyzed by Type I-III), asymmetric (Rme2a/ADMA, Type I enzymes)-, or symmetric (Rme2s/SDMA, Type II enzymes) dimethylation of arginine. Despite many studies, a thorough integration of PRMT enzyme substrate determination and proteomic and transcriptomic consequences of inhibiting Type I and II PRMTs is lacking. To characterize cellular substrates for Type I (Rme2a) and Type II (Rme2s) PRMTs, human A549 lung adenocarcinoma cells were treated with either Type I (MS023) or Type II (GSK591) inhibitors. Using total proteome hydrolysis, we developed a new mass spectrometry approach to analyze total arginine and lysine content. We showed that Rme1 was a minor population (∼0.1% of total arginine), Rme2a was highly abundant (∼1.1%), and Rme2s was intermediate (∼0.4%). While Rme2s was mostly eliminated by GSK591 treatment, total Rme1 and Rme2a were more resistant to perturbation. To quantitatively characterize substrate preferences of the major enzymes PRMT1, PRMT4(CARM1), and PRMT5, we used oriented peptide array libraries (OPAL) in methyltransferase assays. We demonstrated that while PRMT5 tolerates aspartic acid residues in the substrate, PRMT1 does not. Importantly, PRMT4 methylated previously uncharacterized hydrophobic motifs. To integrate our studies, we performed PTMScan on PRMT-inhibited A549 cells and enriched for methylated arginine containing tryptic peptides. For detection of highly charged peptides, a method to analyze the samples using electron transfer dissociation was developed. Proteomic analysis revealed distinct methylated species enriched in nuclear function, RNA-binding, intrinsically disordered domains, and liquid-liquid phase separation. Parallel studies with proteomics and RNA-Seq revealed distinct, but ontologically overlapping, consequences to PRMT inhibition. Overall, we demonstrate a wider PRMT substrate diversity and methylarginine functional consequence than previously shown.