gebhart/patrepeval huggingface dataset:
Role of Axonal NaV1.6 Sodium Channels in Action Potential Initiation of CA1 Pyramidal Neurons (2008)

In many neuron types, the axon initial segment (AIS) has the lowest threshold for action potential generation. Its active properties are determined by the targeted expression of specific voltage-gated channel subunits. We show that the Na+ channel NaV1.6 displays a striking aggregation at the AIS of cortical neurons. To assess the functional role of this subunit, we used Scn8amed mice that are deficient for NaV1.6 subunits but still display prominent Na+ channel aggregation at the AIS. In CA1 pyramidal cells from Scn8amed mice, we found a depolarizing shift in the voltage dependence of activation of the transient Na+ current (INaT), indicating that NaV1.6 subunits activate at more negative voltages than other NaV subunits. Additionally, persistent and resurgent Na+ currents were significantly reduced. Current-clamp recordings revealed a significant elevation of spike threshold in Scn8amed mice as well as a shortening of the estimated delay between spike initiation at the AIS and its arrival at the soma. In combination with simulations using a realistic computer model of a CA1 pyramidal cell, our results imply that a hyperpolarized voltage dependence of activation of AIS NaV1.6 channels is important both in determining spike threshold and localizing spike initiation to the AIS. In addition to altered spike initiation, Scn8amed mice also showed a strongly reduced spike gain as expected with combined changes in persistent and resurgent currents and spike threshold. These results suggest that NaV1.6 subunits at the AIS contribute significantly to its role as spike trigger zone and shape repetitive discharge properties of CA1 neurons.
TGF-β/Smad signaling during hepatic fibro-carcinogenesis (Review) (2014)

After hepatitis virus infection, plasma transforming growth factor (TGF)-β increases in either the acute or chronic inflammatory microenvironment. Although TGF-β is upregulated in patients with hepatocellular carcinoma, it is one of the most potent growth inhibitors for hepatocytes. This cytokine also upregulates extracellular matrix (ECM) production of hepatic stellate cells. Therefore, TGF-β is considered to be the major factor regulating liver carcinogenesis and accelerating liver fibrosis. Smad2 and Smad3 act as the intracellular mediators of TGF-β signal transduction pathway. We have generated numerous antibodies against individual phosphorylation sites in Smad2/3, and identified 3 types of phosphorylated forms (phospho-isoforms): COOH-terminally phosphorylated Smad2/3 (pSmad2C and pSmad3C), linker phosphorylated Smad2/3 (pSmad2L and pSmad3L) and dually phosphorylated Smad2/3 (pSmad2L/C and pSmad3L/C). These Smad phospho-isoforms are categorized into 3 groups: cytostatic pSmad3C signaling, mitogenic pSmad3L signaling and invasive/fibrogenic pSmad2L/C signaling. In this review, we describe differential regulation of TGF-β/Smad signaling after acute or chronic liver injuries. In addition, we consider how chronic inflammation associated with hepatitis virus infection promotes hepatic fibrosis and carcinogenesis (fibro-carcinogenesis), focusing on alteration of Smad phospho-isoform signaling. Finally, we show reversibility of Smad phospho-isoform signaling after therapy against hepatitis virus infection.
Vasculogenic mimicry in small cell lung cancer (2016)

Small cell lung cancer (SCLC) is characterized by prevalent circulating tumour cells (CTCs), early metastasis and poor prognosis. We show that SCLC patients (37/38) have rare CTC subpopulations co-expressing vascular endothelial-cadherin (VE-cadherin) and cytokeratins consistent with vasculogenic mimicry (VM), a process whereby tumour cells form 'endothelial-like' vessels. Single-cell genomic analysis reveals characteristic SCLC genomic changes in both VE-cadherin-positive and -negative CTCs. Higher levels of VM are associated with worse overall survival in 41 limited-stage patients' biopsies (P<0.025). VM vessels are also observed in 9/10 CTC patient-derived explants (CDX), where molecular analysis of fractionated VE-cadherin-positive cells uncovered copy-number alterations and mutated TP53, confirming human tumour origin. VE-cadherin is required for VM in NCI-H446 SCLC xenografts, where VM decreases tumour latency and, despite increased cisplatin intra-tumour delivery, decreases cisplatin efficacy. The functional significance of VM in SCLC suggests VM regulation may provide new targets for therapeutic intervention.
Robust recovery of synthetic aperture radar data from uniformly under-sampled measurements (2011)

In this paper, we propose a novel robust sparse-recovery technique that allows sub-Nyquist uniform under-sampling of wide-bandwidth radar data in real time (single observation). Although much of the information is lost in the received signal due to the low sampling rate, we hypothesize that each wide- bandwidth radar data record can be modeled as a superposition of many backscattered signals from reflective point targets in the scene. In other words, our proposed technique is based on direct sparse recovery via orthogonal matching pursuit using a special dictionary containing many time-delayed versions of the transmitted probing signal. Using data from the U.S. Army Research Laboratory (ARL) Ultra-Wideband (UWB) synthetic aperture radar (SAR), we show that the proposed sparse-recovery model- based (SMB) technique successfully models and synthesizes the returned radar data from real-world scenes using only an analytical waveform that models the transmitted signal and a handful of reflectivity coefficients. More importantly, the reconstructed SAR imagery using the SBM technique with data sampled at only 20% of the original sampling rate has a comparable signal-to-noise ratio (SNR) to the original SAR imagery. For comparison purpose, the paper also presents SAR images recovered from conventional interpolation techniques and the standard random projection based compressed sensing technique, both of which resulted in very poor SAR image quality at the same sub-Nyquist sampling rate (20%).
Identification of Arabidopsis Ethylene-Responsive Element Binding Factors with Distinct Induction Kinetics after Pathogen Infection, (2002)

Ethylene-responsive element binding factors (ERF) proteins are plant-specific transcription factors, many of which have been linked to stress responses. We have identified four Arabidopsis ERF genes whose expression was specifically induced by avirulent and virulent strains of the bacterial pathogen Pseudomonas syringae pv tomato, with overlapping but distinct induction kinetics. However, a delay in ERF mRNA accumulation after infection with the virulent strain was observed when compared with the avirulent strain. The induction of ERF gene expression in most cases preceded the mRNA accumulation of a basic chitinase gene, a potential downstream target for one or more of these ERFs. The expression of the ERF genes was examined among different Arabidopsis tissues, in response to the signaling molecules ethylene, methyl jasmonate, and salicylic acid (SA), and in Arabidopsis mutants with decreased or enhanced susceptibility to pathogens, and significant differences were observed. For example, in seedlings, some of the ERF genes were not induced by SA in the wild-type but were SA responsive in the pad4-1 mutant, suggesting that PAD4-1, which acts upstream of SA accumulation, is also involved in repressing the SA-induced expression of specific ERF genes. The four ERF proteins were shown to contain transcriptional activation domains. These results suggest that transcriptional activation cascades involving ERF proteins may be important for plant defense to pathogen attack and that some ERF family members could be involved in the cross-talk between SA- and jasmonic acid-signaling pathways.
Human cerebral cortical cell lines from patients with unilateral megalencephaly and Rasmussen's encephalitis (1994)

Continuous cerebral cortical cell lines have been developed from two patients, an 11-month-old with unilateral megalencephaly and a seven-year-old with Rasmussen's encephalitis, designated HCN-1 and HCN-2, respectively. The two cell lines stain for neuronal markers such as neurofilament and neuron-specific enolase but not for non-neuronal markers such as glial fibrillary acidic protein and S-100 protein. In the presence of appropriate growth factors, the cells extend long, branched processes resembling neurons. Differentiation of HCN-1 cells can be induced with nerve growth factor, dibutyryl cyclic AMP and isobutylmethylxanthine, while for HCN-2 cells nerve growth factor, isobutylmethylxanthine and the phorbol ester 12-O-tetradecaoylphorbol-13-acetate are most effective. Immunohistochemical staining of both differentiated cell lines reveals intense staining for GABA, glutamate, somatostatin, cholecystokinin-8 and methionine enkephalin. Two human cortical neuronal cell lines have been developed which represent neuronal precursors. These cell lines propagate in culture and are capable of differentiating upon the addition of a variety of growth factors and chemical agents. These cell lines should prove to be useful models for the study of in vitro neuronal processes.
Handbook of Pharmaceutical Analysis (2001)

Form Selection of Pharmaceutical Compounds, A.W. Newman and G.P. Stahly Preparation of Drug Samples for Analysis, D.E. Nadig High-Performance Liquid Chromatography, T.H. Stout and J.G. Dorsey Mass Spectrometry in Pharmaceutical Analysis, F.J. Belas and I.A. Blair Ultraviolet-Visible Spectroscopy, J.H. Miyawa and S.G. Schulman Immunoassay Techniques, J.W. Lee and W.A. Colburn Applications of Capillary Electrophoresis Technology in the Pharmaceutical Industry, C.J. Shaw and N.A. Guzman Atomic Spectroscopy, H.E. Taylor and S.G. Schulman Luminescence Spectroscopy, J.H. Miyawa and S.G. Schulman Solid-State Nuclear Magnetic Resonance Spectroscopy, D.E. Bugay Vibrational Spectroscopy, D.E. Bugay and W.P. Findlay Statistical Considerations in Pharmaceutical Process Development and Validation, G.J. Mergen Drug Index Subject Index
Therapy through chaperones: Sense or antisense? Cystic fibrosis as a model disease (2006)

Massive production and accumulation of a single abnormal protein may constitute a major toxic burden for the cell and even compromise the organism's long-term viability. Consequently, adaptation and survival have forced evolution to create 'quality control' mechanisms that detect, monitor, and often degrade such abnormally folded gene products, in which molecular chaperones are key players. Notwithstanding this, there are numerous examples of misfolded proteins which, in spite of being recognized as aberrant and efficiently discarded by cellular quality control, still retain some of the functional properties of their wild-type counterparts, so that their maintenance in the cell would be beneficial for the organism. Herein are described the cellular roles of molecular chaperones and some new insights on the mechanisms by which they influence the development of human diseases caused by mutations that lead to protein misfolding. A special emphasis is given to cystic fibrosis, a classical genetic disorder resulting from the retention and degradation of a mutant, albeit functional, protein by the endoplasmic reticulum quality control. This particular system has been a good example to describe the mechanisms that are likely to be shared by a number of protein substrates, to define the common characteristics of the mutants, as well as to identify the mechanistic intervenients in their retention and degradation. Finally, new approaches aimed at correcting protein folding defects are discussed, including the potential of molecular chaperones (e.g., through RNA interference) as novel therapeutic targets, and the usage of chemical or pharmacological chaperones as new therapeutic agents.
DFT Calculations Indicate that 1,4‐Dihydropyridine Is a Promising Lead Antioxidant (2004)

Abstract By density‐functional‐theory (DFT) calculations, 1,4‐dihydropyridine ( 1 ) was found to be a powerful lead antioxidant with high H‐atom‐donating ability and relatively low pro‐oxidant activity. Moreover, two ethoxycarbonyl (EtOCO) substituents at C(2) and C(6) should further enhance its H‐atom‐donating ability due to resonance effects.
Collecting and Analyzing Data from Smart Device Users with Local Differential Privacy (2016)

Organizations with a large user base, such as Samsung and Google, can potentially benefit from collecting and mining users' data. However, doing so raises privacy concerns, and risks accidental privacy breaches with serious consequences. Local differential privacy (LDP) techniques address this problem by only collecting randomized answers from each user, with guarantees of plausible deniability; meanwhile, the aggregator can still build accurate models and predictors by analyzing large amounts of such randomized data. So far, existing LDP solutions either have severely restricted functionality, or focus mainly on theoretical aspects such as asymptotical bounds rather than practical usability and performance. Motivated by this, we propose Harmony, a practical, accurate and efficient system for collecting and analyzing data from smart device users, while satisfying LDP. Harmony applies to multi-dimensional data containing both numerical and categorical attributes, and supports both basic statistics (e.g., mean and frequency estimates), and complex machine learning tasks (e.g., linear regression, logistic regression and SVM classification). Experiments using real data confirm Harmony's effectiveness.
Role of NF-kappaB-mediated interleukin-8 expression in intraocular neovascularization. (1998)

These results suggest that IL-8 induced by hypoxia and mediated by NF-kappaB may contribute to the pathogenesis of intraocular neovascularization.
Effect of Wideband Beam Squint on Codebook Design in Phased-Array Wireless Systems (2016)

Analog beamforming with phased arrays is a promising technique for 5G wireless communication at millimeter wave frequencies. Using a discrete codebook consisting of multiple analog beams, each beam focuses on a certain range of angles of arrival or departure and corresponds to a set of fixed phase shifts across frequency due to practical hardware considerations. However, for sufficiently large bandwidth, the gain provided by the phased array is actually frequency dependent, which is an effect called beam squint, and this effect occurs even if the radiation pattern of the antenna elements is frequency independent. This paper examines the nature of beam squint for a uniform linear array (ULA) and analyzes its impact on codebook design as a function of the number of antennas and system bandwidth normalized by the carrier frequency. The criterion for codebook design is to guarantee that each beam's minimum gain for a range of angles and for all frequencies in the wideband system exceeds a target threshold, for example 3 dB below the array's maximum gain. Analysis and numerical examples suggest that a denser codebook is required to compensate for beam squint. For example, 54% more beams are needed compared to a codebook design that ignores beam squint for a ULA with 32 antennas operating at a carrier frequency of 73 GHz and bandwidth of 2.5 GHz. Furthermore, beam squint with this design criterion limits the bandwidth or the number of antennas of the array if the other one is fixed.
An Efficient Algorithm for Mining Association Rules in Large Databases (1995)

Mining for a.ssociation rules between items in a large database of sales transactions has been described as an important database mining problem. In this paper we present an effi-cient algorithm for mining association rules that is fundamentally different from known al-gorithms. Compared to previous algorithms, our algorithm not only reduces the I/O over-head significantly but also has lower CPU overhead for most cases. We have performed extensive experiments and compared the per-formance of our algorithm with one of the best existing algorithms. It was found that for large databases, the CPU overhead was re-duced by as much as a factor of four and I/O was reduced by almost an order of magnitude. Hence this algorithm is especially suitable for very large size databases. 1
Phase I/II trial of IMMU-132 (isactuzumab govitecan), an anti-Trop-2-SN-38 antibody drug conjugate (ADC): Results in patients with metastatic gastrointestinal (GI) cancers. (2015)

703 Background: Trop-2 is a tumor-associated glycoprotein highly expressed in many epithelial cancers. Elevated expression has been linked to more aggressive disease and a poorer prognosis. IMMU-132 is an ADC comprising a humanized mAb binding to Trop-2 and conjugated to SN-38 (drug: Ab ratio = 7.6), the active metabolite of irinotecan. After finding potent activity in human tumor xenografts, a phase I/II trial was undertaken (NCT01631552). Methods: Pts with relapsed/refractory metastatic cancers were enrolled, starting at a dose of 8 mg/kg given on days 1 and 8 of a 3-week cycle. Dose levels of 8 and 10 mg/kg were chosen for phase II (N=47). Results: Sixty pts with advanced GI cancers were enrolled in phase I/II. Neutropenia was the principal dose-limiting toxicity, with fatigue, diarrhea, nausea, and vomiting as other reported toxicities. In the phase II pts with median prior therapies of 3 (range 1-7), the following moderate/severe drug-related toxicities occurred: neutropenia (Gr 3, 18.8%; Gr 4, 10.4%); fatigue (Gr 3, 14.6%; Gr 4, 0%), anemia (Gr 3, 10.4%; Gr 4, 0%); diarrhea (Gr 3, 4.2%; Gr 4, 0%). Of 29 CRC pts (10 mg/kg [N=9], 8 mg/kg [N=20]), 1 had a PR and 14 had SD as the best response by RECIST, with a time to progression (TTP) of 11.5+ months (mo) for the PR (65% shrinkage) and a median of 4.8+ mo for the SD pts (5 ongoing). This is a disease control rate (DCR) of 51.7%. Thirteen CRC pts had KRAS mutations, 7 with SD (median TTP = 4.4+ mo [range, 2.8-7.8 mo; 3 ongoing]). Of 15 pts with pancreatic ca, 8 had SD as best RECIST response (median TTP = 3.4 mo); DCR=53.3%. Among 11 pts with esophageal ca, 7 had CT assessments with 1 PR (TTP, 6.9+ mo), and 4 SD (TTP, 4.0+, 5.0, 6.0, and 6.9 mo) as best response; DCR=62.5%. Of 5 gastric ca pts, only 3 had post-baseline CT assessments, all with SD (1 with 19% target lesion reduction and an ongoing TTP of 6.7+ mo). Conclusions: IMMU-132 is a novel anti-cancer therapeutic, conjugating a topoisomerase I inhibitor to an internalizing, cancer-selective mAb. This ADC can be given safely and repeatedly over many months to heavily pretreated patients. Encouraging activity in pts with several metastatic gastrointestinal tumors has been observed. Clinical trial information: NCT01631552.
Novel microfluidic platform for automated lab-on-chip testing of hypercoagulability panel (2012)

Current methods for hypercoagulability panel testing require large blood volumes and long turn-around testing times. A novel microfluidic platform has been designed to perform automated multiplexed hypercoagulability panel testing at near patient, utilizing only a single droplet of blood sample. We test the hypothesis that this novel platform could be utilized to perform specific multiplexed ELISA-based hypercoagulability panel testing for antithrombin III, protein C, protein S and factor VIII antigens, as well as anticardiolipin/human anti-β2-glycoprotein-1 IgG antibodies--on blood samples. Sandwich ELISA was modified by utilizing magnetic beads coated with specific antibodies as the solid phase using fluorescence readout. Percentage recovery was calculated using four-parameter logistic curves. On-chip ELISA with single factors was compared with multiplex factor ELISA for known concentrations of sample. Blood samples were analyzed on-chip and compared with traditional bench-top assays. Time for multiplexed performance of hypercoagulability panel ELISA on-chip with controls is 72 min. Recovery rates (range 80-120%) for known concentrations of specific factors was not significantly different when assays were performed using a single factor vs. multiplex factor analysis. Assay results were not significantly different between individual assays performed either on bench-top or on-chip with patient blood and/or plasma. Utilizing a novel digital microfluidic platform, we demonstrate the feasibility of automated hypercoagulability panel testing on small volume of plasma and whole blood patient samples with high fidelity. Further investigation is required to test the application of this novel technology at point-of-care clinical settings.
TAS-MRAM based Non-volatile FPGA logic circuit (2007)

As one of the most promising spintronics applications, MRAM combines the advantages of high writing and reading speed, limitless endurance and non-volatility. The integration of MRAM in FPGA allows the logic circuit to rapidly configure the algorithm, the routing and logic functions, easily realize the dynamical reconfiguration and multi-context configuration. However, the conventional MRAM technology based on field induced magnetic switching (FIMS) writing approach consumes very high power and large circuit surface, and produces high disturbance between memory cells. These drawbacks prevent FIMS-MRAM's further development in memory and logic circuit. Thermally assisted switching (TAS) based MRAM is then evaluated to address these issues and some design techniques for FPGA logic circuits based on TAS-MRAM technology are presented. By using STMicroelectronics CMOS 90 nm technology, some chip characteristic results have been calculated to demonstrate the expected performance of TAS-MRAM based FPGA logic circuits.
Processing and characterization of ultralow-dielectric constant organosilicate (2001)

A class of nanoporous organosilicate has been developed that can reach an ultralow-dielectric constant (k⩽2). In this approach a series of triblock polymers, poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) (PEO-b-PPO-b-PEO), are used as sacrificial materials in silicon based spin-on matrices, poly(methylsilsesquioxane) (MSQ) to generate pores when heated above 400 °C. To improve the electrical and mechanical properties, different parameters, such as temperatures, heating rates, polymer molecular weights, copolymer compositions, and the molecular weight of MSQ prepolymers, were studied. Heating temperatures and ramping rates have no large effect on dielectric constants and dielectric breakdown strength. However, at a higher temperature, 500 °C, the mechanical properties are found stronger than those from 400 °C. A higher molecular weight of MSQ prepolymer will also lead to higher mechanical properties of the final porous MSQ, while no temperature effect is observed. Block copolymers with different molecular weights and compositions give similar dielectric constants depending on the polymer loading in MSQ and no substantial change in the dielectric strength of the films with different compositions.
Delaunay Meshing of Piecewise Smooth Complexes without Expensive Predicates (2009)

Recently a Delaunay refinement algorithm has been proposed that can mesh piecewise smooth complexes which include polyhedra, smooth and piecewise smooth surfaces, and non-manifolds. However, this algorithm employs domain dependent numerical predicates, some of which could be computationally expensive and hard to implement. In this paper we develop a refinement strategy that eliminates these complicated domain dependent predicates. As a result we obtain a meshing algorithm that is practical and implementation-friendly.
Waveguide Panel Display Using Electromechanical Spatial Modulators (1998)

Abstract A novel micro‐electro‐mechanical system (MEMS) approach in waveguide panel displays (WPD) is described. High efficiency electromechanical spatial modulators, based on the use of frustrated total internal reflection, were demonstrated. Potential applications of the new display in HDTV using solid‐state light emitting diode (LED) as a light source are discussed.