gebhart/patrepeval huggingface dataset:
Acalabrutinib (ACP-196): A Covalent Bruton Tyrosine Kinase Inhibitor with a Differentiated Selectivity and In Vivo Potency Profile (2017)

Several small-molecule Bruton tyrosine kinase (BTK) inhibitors are in development for B cell malignancies and autoimmune disorders, each characterized by distinct potency and selectivity patterns. Herein we describe the pharmacologic characterization of BTK inhibitor acalabrutinib [compound 1, ACP-196 (4-[8-amino-3-[(2<i>S</i>)-1-but-2-ynoylpyrrolidin-2-yl]imidazo[1,5-<i>a</i>]pyrazin-1-yl]-<i>N</i>-(2-pyridyl)benzamide)]. Acalabrutinib possesses a reactive butynamide group that binds covalently to Cys481 in BTK. Relative to the other BTK inhibitors described here, the reduced intrinsic reactivity of acalabrutinib helps to limit inhibition of off-target kinases having cysteine-mediated covalent binding potential. Acalabrutinib demonstrated higher biochemical and cellular selectivity than ibrutinib and spebrutinib (compounds 2 and 3, respectively). Importantly, off-target kinases, such as epidermal growth factor receptor (EGFR) and interleukin 2-inducible T cell kinase (ITK), were not inhibited. Determination of the inhibitory potential of anti-immunoglobulin M-induced CD69 expression in human peripheral blood mononuclear cells and whole blood demonstrated that acalabrutinib is a potent functional BTK inhibitor. In vivo evaluation in mice revealed that acalabrutinib is more potent than ibrutinib and spebrutinib. Preclinical and clinical studies showed that the level and duration of BTK occupancy correlates with in vivo efficacy. Evaluation of the pharmacokinetic properties of acalabrutinib in healthy adult volunteers demonstrated rapid absorption and fast elimination. In these healthy individuals, a single oral dose of 100 mg showed approximately 99% median target coverage at 3 and 12 hours and around 90% at 24 hours in peripheral B cells. In conclusion, acalabrutinib is a BTK inhibitor with key pharmacologic differentiators versus ibrutinib and spebrutinib and is currently being evaluated in clinical trials.
On the Mechanism of Uptake of Globular Proteins by Polyelectrolyte Brushes:  A Two-Gradient Self-Consistent Field Analysis (2007)

We present model calculations for the interaction of a protein-like inhomogeneously charged nanoscale object with a layer of densely grafted polyelectrolytes ("polyelectrolyte brush"). The motivation of this work is the recent experimental observation that proteins that carry an overall negative charge are absorbed into negatively charged polyelectrolyte brushes. Two-gradient self-consistent field (2G-SCF) calculations have been performed to unravel the physical mechanism of the uptake of protein thus effected. Our results prove that an overall neutral, protein-like object can electrostatically be attracted and therefore spontaneously driven into a polyelectrolyte brush when the object has two faces (patches, domains), one with a permanent positive charge and the other with a permanent negative charge. Using a 2G-SCF analysis, we evaluate the free energy of insertion, such that the electric dipole of the inclusion is oriented parallel to the brush surface. An electroneutral protein-like object is attracted into the brush because the polyelectrolyte brush interacts asymmetrically with the charged patches of opposite sign. At high ionic strength and low charge density on the patches, the attraction cannot compete with the repulsive excluded-volume interaction. However, for low ionic strengths and sufficiently high charge density on the patches, a gain on the order of k(B)T per charge becomes possible. Hence, the asymmetry of interaction for patches of different charges may result in a total attractive force between the protein and the brush. All results obtained herein are in excellent agreement with recent experimental data.
Satellite Jitter Estimation and Validation Using Parallax Images (2017)

Satellite jitter (SJ) is an important error source that affects the geometric accuracy of high resolution satellite imagery. In this paper, the quantitative relationship between the jitter displacement (image displacement caused by SJ) and relative registration error obtained from parallax images is deduced to be theoretical in detail, and the jitter displacement estimation model is built to estimate the jitter displacement. Then, a simulation experiment is carried out to validate the feasibility of using the built jitter displacement estimation model to estimate the jitter displacement. Finally, experiments with real images in DengFeng (China) including multispectral images of Ziyuan-3 (ZY-3) satellite and high resolution (HR) images of Ziyuan1-02C (ZY1-02C) satellite are used to validate the effectiveness of utilizing the built jitter displacement estimation model to do the jitter estimation. High accuracy ground reference data are further used to evaluate the accuracy of the estimation. Experimental results show that the average estimated error for jitter displacement of ZY-3 is 2.96% and 0.11% in amplitude and frequency respectively, and the estimated error for jitter displacement of ZY1-02C is 8.46% and 0.35% in amplitude and frequency, respectively.
A Lightweight Process for Change Identification and Regression Test Selection in Using COTS Components (2006)

Various regression test selection techniques have been developed and have shown fault detection effectiveness. The majority of these test selection techniques rely on access to source code for change identification. However, when new releases of COTS components are made available for integration and testing, source code is often not available. In this paper, we present a lightweight integrated-black-box approach for component change identification (I-BACCI) process for selection of regression tests for user/glue code that uses COTS components. I-BACCI is applicable when component licensing agreements do not preclude analysis of the binary files. A case study of the process was conducted on an ABB product that uses a medium-scale internal ABB software component. Five releases of the component were examined to evaluate the efficacy of the proposed process. The result of the case study indicates this process can reduce the required number of regression tests by 54% on average.
Poly (&epsilon;-caprolactone) nanofibrous ring surrounding a polyvinyl alcohol hydrogel for the development of a biocompatible two-part artificial cornea (2011)

The study aimed to fabricate and characterize a 2-part artificial cornea as a substitute for penetrating keratoplasty in patients with corneal blindness. The peripheral part of the artificial cornea consisted of plasma-treated electrospun poly (ɛ-caprolactone) (PCL) nanofibers, which were attached to a hydrogel disc of polyvinyl alcohol (PVA) as a central optical part. The physical properties of the prepared artificial cornea, including morphology, mechanical properties, light transmittance, and contact angle, were assessed. Cell attachment and proliferation studies were performed on rabbit limbal stem cells. The SEM image of the polymeric system showed that the peripheral part formed a highly porous scaffold that could facilitate tissue biointegration. Assessment of the mechanical properties of the peripheral nanofibrous part and the hydrogel optical part showed suitable elasticity. Young's modulus values of the electrospun PCL skirt and PVA hydrogel core were 7.5 and 5.3 MPa, respectively, which is in line with the elasticity range of natural human cornea (0.3-7 MPa). The light transmittance of the central part was >85% when measured in the 400-800 nm wavelength range. The plasma-treated PCL nanofibrous scaffold promoted limbal stem cell adhesion and proliferation within 10 days. These results confirmed that the polymeric artificial cornea showed suitable physical properties and good biocompatibility and epithelialization ability.
Incomplete Information, Heterogeneity, and Asset Pricing (2005)

We consider a pure exchange economy where the drift of aggregate consumption is unobservable. Agents with heterogeneous beliefs and preferences act competitively on financial and goods markets. We discuss how equilibrium market prices of risk differ across agents, and in particular we discuss the properties of the market price of risk under the physical (objective) probability measure. We propose a number of specifications of risk aversions and beliefs where the market price of risk is much higher, and the riskless rate of return lower, than in the equivalent full information economy (homogeneous and heterogeneous preferences) and thus can provide an(other) answer to the equity premium and risk-free rate puzzles. We also derive a representation of the equilibrium volatility and numerically assess the role of heterogeneity in beliefs. We show that a high level of stock volatility can be obtained with a low level of aggregate consumption volatility when beliefs are heterogeneous. Finally, we discuss how incomplete information may explain the apparent predictability in stock returns and show that in-sample predictability cannot be exploited by the agents, as it is in fact a result of their learning processes. Copyright 2006, Oxford University Press.
Transverse mode electrostatic microactuator for MEMS-based HDD slider (2002)

In this paper, we propose a new head slider concept for hard disk drives (HDDs) which will be completely batch-fabricated on a sacrificial layer together with a transverse mode electrostatic microactuator using MEMS-based technology. We present the design, fabrication, and testing of a prototype electrostatic microactuator in transverse mode without a slider body just to determine the basic characteristics. Test results showed a stroke of 0.55 /spl mu/m and a very high mechanical resonant frequency of 34 kHz due to the low moving mass of 0.85 /spl mu/g and the large force, estimated to be 23.5 /spl mu/N, generated by the actuator.
Cole–Cole parameters for the dielectric properties of porcine tissues as a function of age at microwave frequencies (2010)

We have applied the Cole-Cole expression to the dielectric properties of tissues in the frequency range 0.4-10 GHz. The data underpinning the model relate to pig tissue as a function of age. Altogether, we provide the Cole-Cole parameters for 14 tissue types at three developmental stages.
Coupled Subspaces Analysis (2004)

Subspace learning is a fundamental approach for face recognition and facial expression analysis. In this paper, we propose a novel subspace analysis scheme for the two applications. Unlike the traditional subspace algorithms, such as PCA and LDA, in which an image is treated as a vector; in our scheme, an image is directly treated as a 2D matrix, and a new criterion is proposed to infer two low dimensional coupled subspaces that optimally reconstruct the original matrices from row and column directions collaboratively. An efficient approach, namely Coupled Subspace Analysis (CSA), is applied to learn these two subspaces in an iterative manner. Then we reveal the essence of each step in CSA and propose an approach to select the dimension numbers for these two subspaces with the given rate of information lost. Moreover, we prove that PCA and the recently proposed 2DPCA are just simplified special cases of CSA and answer the unsolved theoretical problems in 2DPCA. The main contributions of this paper include: 1) for both face recognition and facial expression analysis, we propose a novel image matrix based scheme, and obtain a much lower dimensional face representation for subsequent discriminant analysis; 2) CSA effectively alleviates the curse of dimensionality dilemma and small sample size problem existed in face recognition problem; and 3) CSA clarifies the essence of 2DPCA and explains the superiority of 2DPCA compared with PCA. The extensive experiments on both face recognition and facial expression analysis demonstrate that CSA is superior to the classical algorithms.
Solution-Phase Parallel Synthesis and SAR of Homopiperazinyl Analogs as Positive Allosteric Modulators of mGlu<sub>4</sub> (2011)

Using a functional high-throughput screening (HTS) and subsequent solution-phase parallel synthesis approach, we have discovered a novel series of positive allosteric modulators for mGlu₄, a G-protein coupled receptor. This series is comprised of a homopiperazine central core. The solution-phase parallel synthesis and SAR of analogs derived from this series will be presented. This series of positive allosteric modulators of mGlu₄ provide critical research tools to further probe the mGlu₄-mediated effects in Parkinson's disease.
Cognitive activities and support in debugging (2002)

Features of debugging aids have been currently developed to facilitate the debugging process at times without explicit cognitive considerations. We investigate the design rationale for developing debugging aids and analyze the role of debugging tools available today. By investigating the programmers' debugging process, we analyze the process of debugging and how debugging aids can help programmers. Debugging is performed mainly through the comprehension and isolation strategies along with abstractions. While debugging tools including tracing memory viewing, control flow graphs, and visualizations support the comprehension strategy, functions such as backtracking and breakpoints facilitate the isolation strategy. Debugging aids should help programmers enhance their understanding of the program and facilitate the process of gathering clues and searching for, and identifying the bug. Finally, we provide some suggestions on building more sophisticated debugging aids.
Rhodium Complexes with the New Anionic Diphosphine [7,8-(PPh<sub>2</sub>)<sub>2</sub>-7,8-C<sub>2</sub>B<sub>9</sub>H<sub>10</sub>]<sup>-</sup>Ligand (1996)

New rhodium complexes with the eclipsed anionic diphosphine [7,8-(PPh2)2-7,8-C2B9H10]- are described. These were prepared from the neutral cod complex [Rh{7,8-(PPh2)2-7,8-C2B9H10}(cod)] either directly or via the complex [Rh{7,8-(PPh2)2-7,8-C2B9H10}(CO)2], which was obtained by bubbling CO through a suspension of [Rh{7,8-(PPh2)2-7,8-C2B9H10}(cod)] in deoxygenated methanol. The CO ligands may be readily replaced by monophosphines, chelating diphosphines, monoamines, and chelating diamines. CO substitution by monophosphines depends on the phosphine cone angle more than the phosphine basicity. Both CO ligands can be replaced in [Rh{7,8-(PPh2)2-7,8-C2B9H10}(CO)2] by monophosphines with small cone angles, while monophosphines with large cone angles are only able to displace one CO ligand. Thus [Rh{7,8-(PPh2)2-7,8-C2B9H10}(CO)(phosphine)] and [Rh{7,8-(PPh2)2-7,8-C2B9H10}(phosphine)2] can be obtained. By contrast, with chelating diamines, carbamoyl complexes have been obtained.
Rhodium-Catalyzed Asymmetric 1,4-Addition of Aryltitanium Reagents Generating Chiral Titanium Enolates:  Isolation as Silyl Enol Ethers (2002)

The addition of aryltitanium triisopropoxide (ArTi(OPr-i )3) to alpha,beta-unsaturated ketones proceeded with high enantioselectivity (94-99.8% ee) in the presence of 3 mol % of [Rh(OH)((S )-binap)]2 in THF at 20 degrees C to give high yields of the titanium enolates as 1,4-addition products. The titanium enolates were converted into silyl enol ethers by treatment with chlorotrimethylsilane and lithium isopropoxide.
A phase II, open-label study evaluating the safety and efficacy of ramucirumab combined with mFOLFOX-6 as first-line therapy in patients (pts) with metastatic colorectal cancer (mCRC): CP12-0709/NCT00862784. (2012)

533^ Background: Vascular endothelial growth factor (VEGF) and the VEGF receptor-2 (VEGFR-2) are overexpressed in CRC and mediate angiogenesis. Ramucirumab (RAM; IMC-1121B) is a fully human IgG1 MAb that inhibits binding of VEGF ligands to VEGFR-2 and inhibits VEGFR-2 activation and signaling. In preclinical CRC models VEGFR-2 inhibition confers antitumor activity. RAM was administered with mFOLFOX-6 as 1st-line therapy (rx) in mCRC. Methods: Eligible pts had mCRC with no prior chemo Rx (prior adjuvant rx was allowed), at least 1 measurable target lesion by RECIST v1.0, ECOG PS 0-1, and adequate organ function. Pts received RAM (8 mg/kg IV on D1), oxaliplatin (85 mg/m² IV on D1), folinic acid (400 mg/m² IV on D1), fluorouracil (5-FU, 400 mg/m² bolus followed by 2400 mg/m² continuous infusion over 46 hours on D1). Rx cycles were q2w and tumor assessments were q8w. Endpoints included progression-free survival (PFS), objective response rate (ORR), overall survival (OS), safety, and pharmacokinetics/immunogenicity. Sample size was based on an improved median (medn) PFS from 8 to 11 months (m). Results: 48 pts received therapy. All were white; 25 M/23 F; median age 60.5 y. ECOG PS was 0/1 in 30/18 pts. 42 pts (88%) had metastatic disease, with liver (79%) and lung (35%) as most frequent sites. 13 (27%) pts had liver-only mCRC. The most frequently observed RAM-related adverse events (AEs) included hypertension 46% (15% Grade [G] ≥3); diarrhea 31% (2% G≥3); and nausea and infusion-related reactions, each 19% (0% G≥3). 2 pts died on study due to acute MI or cardiopulmonary arrest. Medn PFS was 11.5 m (9-13 m 95% CI) with 1-yr PFS of 48% (32-62% 95% CI). ORR: 67% (52-80% 95% CI); disease control rate (DCR: CR+PR+SD): 94% (83-99% 95% CI; 5 pts had CR, 27 had PR and 13 had SD). Medn duration of response was 11.0 m (7-12 m 95% CI). One-year OS was 85% (72-93% 95% CI). As of 4/15/2011, 2 pts continued to receive rx, 20 had died and 28 (58.3%) remained alive. Conclusions: RAM combined with mFOLFOX-6 was reasonably tolerated in pts with mCRC. Median PFS exceeds 11 m. PFS, ORR, and DCR are encouraging and favor investigation of this regimen and of RAM in mCRC.
The Glioma-associated Protein SETA Interacts with AIP1/Alix and ALG-2 and Modulates Apoptosis in Astrocytes (2000)

Expression of the src homology 3 (SH3) domain-containing expressed in tumorigenic astrocytes (SETA) gene is associated with the tumorigenic state in astrocytes. SETA encodes a variety of adapter proteins containing either one or two SH3 domains, as suggested by the sequence heterogeneity of isolated cDNAs. Using both SH3 domains in a yeast two-hybrid screen of a glial progenitor cell cDNA library, we isolated the rat homolog of the ALG-2-interacting protein 1 or ALG-2-interacting protein X (AIP1/Alix). In vitro confrontation experiments showed that the SH3-N domain of SETA interacted with the proline-rich C terminus of AIP1. In co-immunoprecipitation experiments, SETA and AIP1 interacted and could form a complex with apoptosis-linked gene 2 protein. Endogenous SETA and AIP1 proteins showed similar patterns of staining in primary rat astrocytes. Misexpression of a variety of SETA protein isoforms in these astrocytes revealed that they localized to the actin cytoskeleton. Furthermore, SETA proteins containing the SH3-N domain were able to sensitize astrocytes to apoptosis induced by UV irradiation. Expression of the isolated SH3-N domain had the greatest effect in these experiments, indicating that interference in the interaction between endogenous SETA and AIP1 sensitizes astrocytes to apoptosis in response to DNA damage.
Standard Test To Characterize Alfalfa Cultivar Tolerance To Intensive Grazing With Continuous Stocking (1998)

Establishment: Land preparation, liming, fertilization, and pest control for establishment and maintenance are the same as those used for any alfalfa yield or performance trial. All entries to be tested, plus a grazing tolerant and intolerant check, are sown at the normal planting date for alfalfa in replicated sward plots (simulate planting with a cultipak seeder) at 15-20 kg ha-1 within a grazing paddock (range 0.5 to 1.5 ha). A minimum of 1.5 X 4.5 m plots with 6 replications is recommended. The actual test should be surrounded on all sides by at least 7.5 m of a border area between the test and any fence used to confine the animals. Drinking water, mineral boxes, supplement feeders, and any shade for the animals should all be located on the same end of the paddock and away from the actual plots.
Picosecond spectral coherent anti-Stokes Raman scattering imaging with principal component analysis of meibomian glands (2011)

The lipid distribution in the mouse meibomian gland was examined with picosecond spectral anti-Stokes Raman scattering (CARS) imaging. Spectral CARS data sets were generated by imaging specific localized regions of the gland within tissue sections at consecutive Raman shifts in the CH(2) stretching vibrational range. Spectral differences between the location specific CARS spectra obtained in the lipid-rich regions of the acinus and the central duct were observed, which were confirmed with a Raman microspectroscopic analysis, and attributed to meibum lipid modifications within the gland. A principal component analysis of the spectral data set reveals changes in the CARS spectrum when transitioning from the acini to the central duct. These results demonstrate the utility of picosecond spectral CARS imaging combined with multivariate analysis for assessing differences in the distribution and composition of lipids in tissues.
Mutational Analysis of Intervening Sequences Connecting the Binding Sites for Integration Host Factor, PepA, PurR, and RNA Polymerase in the Control Region of the <i>Escherichia coli carAB</i> Operon, Encoding Carbamoylphosphate Synthase (2006)

Transcription of the carAB operon encoding the unique carbamoylphosphate synthase of Escherichia coli reflects the dual function of carbamoylphosphate in the biosynthesis of arginine and pyrimidine nucleotides. The tandem pair of promoters is regulated by various mechanisms depending on the needs of both pathways and the maintenance of a pyrimidine/purine nucleotide balance. Here we focus on the linker regions that impose the distribution of target sites for DNA-binding proteins involved in pyrimidine- and purine-specific repression of the upstream promoter P1. We introduced deletions and insertions, and combinations thereof, in four linkers connecting the binding sites for integration host factor (IHF), PepA, PurR, and RNA polymerase and studied the importance of phasing and spacing of the targets and the importance of the nucleotide sequence of the linkers. The two PepA binding sites must be properly aligned and separated with respect to each other and to the promoter for both pyrimidine- and purine-mediated repression. Similarly, the phasing and spacing of the IHF and PEPA2 sites are strictly constrained but only for pyrimidine-specific repression. The IHF target is even dispensable for purine-mediated regulation. Thus, a correct localization of PepA within the higher-order nucleoprotein complex is a prerequisite for the establishment of pyrimidine-mediated repression and for the coupling between purine- and pyrimidine-dependent regulation. Our data also suggest the existence of a novel cis-acting pyrimidine-specific regulatory target located around position -60. Finally, the analysis of a P1 derivative devoid of its control region has led to a reappraisal of the effect of excess adenine on P1 and has revealed that P1 has no need for a UP element.
VLSI for OFDM (1998)

This article discusses the VLSI implications of high-speed coded orthogonal frequency-division multiplexing modulation. This is achieved by looking at practical examples of the computational blocks that constitute a COFDM modem and then examining examples of COFDM chips.
High-resolution scanning microdensitometer (1997)

A technique has been developed to enhance the resolution of an optical scanning microdensitometer. Phase shifting optics are used to obtain a signal with high resolution, but with a complex structure. This signal is subtracted from a reference signal to produce the equivalent of an isolated, very narrow, bright line. This line is then scanned across the specimen. Improvements in resolution of about a factor of 2, compared to a conventional optical system, have been observed at numerical apertures up to 0.55, without sacrificing either the working distance or the depth of focus.