gebhart/patrepeval huggingface dataset:
Identification of new EphA4 inhibitors by virtual screening of FDA-approved drugs (2018)

The receptor tyrosine kinase, erythropoietin-producing hepatocellular A4 (EphA4), was recently identified as a molecular target for Alzheimer's disease (AD). We found that blockade of the interaction of the receptor and its ligands, ephrins, alleviates the disease phenotype in an AD transgenic mouse model, suggesting that targeting EphA4 is a potential approach for developing AD interventions. In this study, we identified five FDA-approved drugs-ergoloid, cyproheptadine, nilotinib, abiraterone, and retapamulin-as potential inhibitors of EphA4 by using an integrated approach combining virtual screening with biochemical and cellular assays. We initially screened a database of FDA-approved drugs using molecular docking against the ligand-binding domain of EphA4. Then, we selected 22 candidate drugs and examined their inhibitory activity towards EphA4. Among them, five drugs inhibited EphA4 clustering induced by ephrin-A in cultured primary neurons. Specifically, nilotinib, a kinase inhibitor, inhibited the binding of EphA4 and ephrin-A at micromolar scale in a dosage-dependent manner. Furthermore, nilotinib inhibited the activation of EphA4 and EphA4-dependent growth cone collapse in cultured hippocampal neurons, demonstrating that the drug exhibits EphA4 inhibitory activity in cellular context. As demonstrated in our combined computational and experimental approaches, repurposing of FDA-approved drugs to inhibit EphA4 may provide an alternative fast-track approach for identifying and developing new treatments for AD.
Surface-Enhanced Raman Scattering of Bacteria in Microwells Constructed from Silver Nanoparticles (2012)

Whole bacterial cell characterization is critically important for fast bacterial identification. Surface-enhanced Raman scattering (SERS) is proven to be powerful technique to serve such a goal. In this study, the characterization of whole bacterial cells in the microwells constructed from colloidal silver nanoparticles (AgNPs) with “convective-assembly” method is reported. The proper size of the microwells for the model bacteria, Escherichia coli and Staphylococcus cohnii , is determined to be 1.2 μ m from their electron microscopy images. A minimum dilution factor of 20 is necessary for the bacterial samples collected from growth media to diminish the bacterial aggregation to place the bacterial cells into the microwells. The constructed microwell structures are tested for their bacterial SERS performance and compared to the SERS spectra obtained from the samples prepared with a simple mixing of bacteria and AgNPs for the same bacteria. The results indicate that microwell structures not only improve the spectral quality but also increase the reproducibility of the SERS spectra.
Experimental Inoculation of Growing Pigs with U.S. Strains of Swine and Human Hepatitis E Viruses (2000)

U.S. strains of swine and human hepatitis E viruses (HEV) are closely related genetically. We found that swine and human HEV differ in virulence and both induce subclinical, but morphologically discernable, hepatitis in experimentally infected SPF pigs. Experimental inoculation of pigs with human HEV may provide a useful model to study the pathogenesis of hepatitis E virus infection and test efficacy of human HEV vaccines.
Regenerating MR Tagged Images Using Harmonic Phase (HARP) Methods (2004)

Magnetic resonance tagging has proven useful in the visualization and quantification of cardiac motion. Traditionally, tags are designed to have crisp geometric profiles in order to enhance both visualization and detection of tags. Recent image acquisition and analysis methods, however, have been designed to exploit sinusoidal tag profiles. This paper presents a method based on harmonic phase (HARP) concepts to synthesize tag lines that have both crisp profiles and alternative orientations from the original sinusoidal patterns. Results are demonstrated on images acquired with SPAMM, CSPAMM, and fast-HARP pulse sequences.
A Mitochondrial Biomarker-Based Study of S-Equol in Alzheimer’s Disease Subjects: Results of a Single-Arm, Pilot Trial (2017)

Reductions in bioenergetic fluxes, mitochondrial enzyme activities, and mitochondrial number are observed in Alzheimer's disease (AD). Preclinical work indicates estrogen pathway signaling by either estrogen or selective β estrogen receptor (ERβ) agonists benefits these parameters. To assess whether an ERβ agonist could improve mitochondrial function in actual AD subjects, we administered S-equol (10 mg twice daily) to 15 women with AD and determined the platelet mitochondria cytochrome oxidase (COX) activity before initiating S-equol (lead-in), after two weeks of S-equol (active treatment), and two weeks after stopping S-equol (wash-out). Because the intra-individual variation of this enzyme across samples taken at different times was unknown we used a nonparametric, single-arm, dichotomous endpoint that classified subjects whose active treatment COX activity exceeded the average of their lead-in and wash-out measures as positive responders. Eleven positive responses were observed (p < 0.06). The implications of this finding on our null hypothesis (that S-equol does not influence platelet mitochondria COX activity) are discussed. To our knowledge, this is the first time a direct mitochondrial target engagement biomarker has been utilized in an AD clinical study.
An organic transistor-based system for reference-less electrophysiological monitoring of excitable cells (2015)

In the last four decades, substantial advances have been done in the understanding of the electrical behavior of excitable cells. From the introduction in the early 70's of the Ion Sensitive Field Effect Transistor (ISFET), a lot of effort has been put in the development of more and more performing transistor-based devices to reliably interface electrogenic cells such as, for example, cardiac myocytes and neurons. However, depending on the type of application, the electronic devices used to this aim face several problems like the intrinsic rigidity of the materials (associated with foreign body rejection reactions), lack of transparency and the presence of a reference electrode. Here, an innovative system based on a novel kind of organic thin film transistor (OTFT), called organic charge modulated FET (OCMFET), is proposed as a flexible, transparent, reference-less transducer of the electrical activity of electrogenic cells. The exploitation of organic electronics in interfacing the living matters will open up new perspectives in the electrophysiological field allowing us to head toward a modern era of flexible, reference-less, and low cost probes with high-spatial and high-temporal resolution for a new generation of in-vitro and in-vivo monitoring platforms.
Above room temperature ferromagnetism in Mn-ion implanted Si (2005)

Above room temperature ferromagnetic behavior is achieved in Si through Mn ion implantation. Three-hundred-keV ${\mathrm{Mn}}^{+}$ ions were implanted to 0.1% and 0.8% peak atomic concentrations, yielding a saturation magnetization of $0.3\phantom{\rule{0.3em}{0ex}}\mathrm{emu}∕\mathrm{g}$ at $300\phantom{\rule{0.3em}{0ex}}\mathrm{K}$ for the highest concentration as measured using a SQUID magnetometer. The saturation magnetization increased by $\ensuremath{\sim}2\ifmmode\times\else\texttimes\fi{}$ after annealing at $800\phantom{\rule{0.2em}{0ex}}\ifmmode^\circ\else\textdegree\fi{}\mathrm{C}$ for $5\phantom{\rule{0.3em}{0ex}}\mathrm{min}$. The Curie temperature for all samples was found to be greater than $400\phantom{\rule{0.3em}{0ex}}\mathrm{K}$. A significant difference in the temperature-dependent remnant magnetization between the implanted p-type and n-type Si is observed, giving strong evidence that a Si-based diluted magnetic semiconductor can be achieved.
A Mixed‐Extractor Strategy for Efficient Sorting of Semiconducting Single‐Walled Carbon Nanotubes (2016)

A general strategy for sorting semiconducting single-walled carbon nanotubes (s-SWNTs) with high efficiency using a mixed-extractor is reported. When the two extractors have a sufficient difference in binding energy with s-SWNTs, and skeleton flexibility, the mixture shows enhanced yield for sorting s-SWNTs. The strategy could be effective when applied to increase the sorting yield of other selective dispersion systems.
Abstract 61: Use of two-color fluorometric real-time PCR to develop molecular diagnostic tests with intrinsic quality control that augment cytomorphologic diagnosis of lung cancer. (2013)

Abstract Quantitative RT-PCR tests that measure transcript abundance of selected genes in clinical specimens promise to improve cancer diagnostic accuracy and enable “personalized medicine” through selection of the most effective treatment for each cancer. However, most clinical samples are Formalin-Fixed, Paraffin-Embedded (FFPE) and these yield sub-optimal RNA integrity. Thus, there is a need for qPCR tests with increased robustness that also have intrinsic quality control and low cost. To address this need, we developed qPCR methods that enable simultaneous measurement of each target gene and reference gene transcript relative to a known number of gene-specific internal standard (IS) molecules using two-color fluorometric analysis on real-time platform. For each gene, a competitive template IS was synthesized containing 4-6 nucleotide changes relative to the native template (NT). During PCR, NT or IS signal was quantified with sequence-specific FAM-labeled probe or Quasar 670-labeled probe, respectively. To optimize measurement sensitivity for analysis of highly degraded FFPE samples; a) each RNA sample was reverse transcribed (RT) with gene-specific primer and b) cDNA was pre-amplified with 18 PCR cycles in the presence of internal standards. Results obtained with pre-amp or no pre-amp conditions were highly correspondent. We conducted a validation study of this assay in 38 samples (10 malignant and 10 benign surgical FFPE tissues and 13 malignant and 5 benign fine needle aspirate (FNA) samples. Consistent with previous results in fresh frozen surgical samples, the lung cancer diagnostic test (LCDT) optimal cut-off value discriminated malignant from non-malignant tissues (p = 0.0009), had 92.9% specificity and 75.0% sensitivity, and a receiver operator characteristic area under the curve of 0.87 (95% confidence interval 0.74-0.99). Based on these data, we expect that this quality-controlled two color fluorometric qPCR approach will enable reliable analysis of the LCDT and other promising qPCR-based molecular diagnostic tests in small degraded RNA extracted from clinical FFPE and FNA cell block FFPE samples. Citation Format: Jiyoun Yeo, Erin L. Crawford, Thomas M. Blomquist, Lauren M. Stanoszek, Rachel E. Dannemiller, Laura Jordan, Jill Zyrek, Luis de la Casas, James C. Willey. Use of two-color fluorometric real-time PCR to develop molecular diagnostic tests with intrinsic quality control that augment cytomorphologic diagnosis of lung cancer. [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 61. doi:10.1158/1538-7445.AM2013-61
Solid acid catalyzed depolymerization of lignin into value added aromatic monomers (2014)

Depolymerization of lignin to produce value-added aromatic monomers has attracted a lot of attention since these monomers can potentially be used as fuel additives (octane enhancers) and in turn can improve the prospects of cellulosic ethanol technology to become economically feasible. Here we show that solid acid catalysts could efficiently convert lignin into value added aromatic monomers with 60% yields and ca. 95% mass balance when depolymerization reactions were carried out at 250 °C for 30–120 minutes. We found that the reaction parameters have a remarkable effect on improving the yields.
Integrated Ultrasound Imaging Systems Based on Capacitive Micromachined Ultrasonic Transducer Arrays (2006)

Capacitive micromachined ultrasonic transducers (CMUTs) overcome many limitations of existing ultrasound transducer technologies enabling new applications of ultrasound, especially for medical imaging and treatment. Some of the most important of these advancements are the ability to fabricate transducer arrays with two dimensional geometries and high operating frequencies. Over the past decade, extensive research has been conducted on the fabrication, characterization, and modelling of CMUTs. Current research efforts focus on the integration of CMUTs in systems for new medical imaging tools. This paper briefly reviews CMUT technology and presents imaging results from two CMUT-based imaging systems. The first system is designed for use within a 5-mm endoscopic channel and is based on a two dimensional, 16-element /spl times/ 16-element, 5-MHz CMUT array. To provide a means of integrating the CMUT array with electronics, each element of the array is connected to a flip-chip bond pad on the back side of the array via a through-wafer interconnect. The array is flip-chip bonded to a custom-designed integrated circuit (IC) that comprises the frontend circuitry for the transducer elements. The array and IC are connected to an FPGA-based data acquisition system that can acquire volumetric imaging data in real time. Volumetric pulse-echo and photoacoustic images obtained with this system are presented. The second system is based on a 64-element, 20-MHz, 2-mm diameter CMUT ring array. This array is also designed for use in catheter-based imaging applications. Ring arrays have the advantage of providing space in the center for a guidewire or other catheter-based instrument. Volumetric images obtained with the ring-array system are also presented.
Single sideband encoder for music coding in cochlear implants (2008)

The restoration of melody perception is a key remaining challenge in cochlear implants. We propose a new sound coding strategy that converts an audio signal into time-varying electrically stimulating pulse trains. A sound is first split into several frequency subbands and each subband signal is coherently downward shifted to a low-frequency base band, similar to demodulation used in single sideband (SSB) radios. These resulting coherent envelope signals have Hermitian symmetric frequency spectrums and are thus real-valued. A peak detector in each subband further converts the coherent envelopes into rate-varying and interleaved pulse trains. Acoustic simulations of cochlear implants with normal hearing listeners showed significant improvement in melody recognition over the most common stimulation approach used in cochlear implants.
Direct in-situ single-shot measurements of the absolute carrier-envelope phases of ultrashort pulses (2019)

Many important physical processes such as nonlinear optics and coherent control are highly sensitive to the absolute carrier-envelope phase (CEP) of driving ultrashort laser pulses. This makes the measurement of CEP immensely important in relevant fields. Even though relative CEPs can be measured with a few existing technologies, the estimate of the absolute CEP is not straightforward and always requires theoretical inputs. Here, we demonstrate a novel in-situ technique based on angular streaking that can achieve such a goal without complicated calibration procedures. Single-shot measurements of the absolute CEP have been achieved with an estimated precision of 0.19 radians.
A Cu/low-κ dual damascene interconnect for high performance and low cost integrated circuits (2002)

Copper and a low dielectric constant (low-/spl kappa/) material have been successfully integrated in a dual damascene interconnect architecture. The low-/spl kappa/ material (/spl kappa/=2.2) was used as intra-level dielectric and inter-level dielectric, which has led to significant reduction in both intra-level and inter-level capacitance. In addition, low Cu wiring resistance and low Cu via resistance have been achieved in the dual damascene interconnect which offers process simplification and low cost.
ChemInform Abstract: Reactivity of Hypervalent Silicon Derivatives. One‐Step Synthesis of Mono‐ and Dihydrogenosilanes. (1989)

Abstract The anionic silicon complexes (I) and (IV) react with the primary alkyl Grignard compounds (II), activated by titanocene dichloride, to form the monohydrogenosilanes (III) and (V) as the main products.
Automating network node behavior characterization by mining communication patterns (2017)

Enterprise networks of scale are complex, dynamic computing environments that respond to evolving business objectives and requirements. Characterizing system behaviors in these environments is essential for network management and cybersecurity operations. Characterization of system's communication is typical and is supported using network flow information (Net-Flow). Related work has characterized behavior using theoretical graph metrics; results are often difficult to interpret by enterprise staff. We propose a different approach, where flow information is mapped to sets of tags that contextualize the data in terms of network principals and enterprise concepts. Frequent patterns are then extracted and are expressed as behaviors. Behaviors can be compared, identifying systems expressing similar behaviors. We evaluate the approach using two case studies.
Barista: A Technique for Recording, Encoding, and Running Platform Independent Android Tests (2017)

Because mobile apps are extremely popular and often mission critical nowadays, companies invest a great deal of resources in testing the apps they provide to their customers. Testing is particularly important for Android apps, which must run on a multitude of devices and operating system versions. Unfortunately, as we confirmed in many interviews with quality assurance professionals, app testing is today a very human intensive, and therefore tedious and error prone, activity. To address this problem, and better support testing of Android apps, we propose a new technique that allows testers to easily create platform independent test scripts for an app and automatically run the generated test scripts on multiple devices and operating system versions. The technique does so without modifying the app under test or the runtime system, by (1) intercepting the interactions of the tester with the app and (2) providing the tester with an intuitive way to specify expected results that it then encode as test oracles. We implemented our technique in a tool named Barista and used the tool to evaluate the practical usefulness and applicability of our approach. Our results show that Barista (1) can faithfully encode user defined test cases as test scripts with built-in oracles that can run on multiple platforms and (2) outperforms two popular tools with similar functionality. Barista and our experimental infrastructure are publicly available.
Molecular analysis of the gene encoding the major surface antigen of <i>Toxoplasma gondii</i>. (1988)

The complete sequence of P30, the major surface Ag of the protozoan parasite, Toxoplasma gondii, has been deduced through the cloning and analysis of its gene. Using polyclonal serum specific for P30, we have isolated a P30 cDNA clone from a lambda gt11 cDNA expression library derived from tachyzoites of T. gondii (RH strain). This clone produces a beta-galactosidase fusion protein which reacts with several anti-P30 mAb. In addition, polyclonal anti-serum raised to the fusion protein reacts with purified P30 protein and exclusively with P30 in a whole cell lysate of T. gondii. This cDNA clone was used to isolate near full-length cDNA molecules and a cosmid clone containing the P30 gene. Sequence analysis of the cDNA reveals a single open reading frame with coding capacity for 34.7 kDa of primary translation product (consistent with the apparent Mr of P30 on SDS-acrylamide gels) including a presumptive hydrophobic signal sequence. The P30 primary translation product also has a carboxy-terminal hydrophobic tail which is predictive of a posttranslational cleavage and modification with a glycolipid anchor. We have identified the apparent 5' and 3' ends of the P30 mRNA transcript which is extremely abundant, 1500 nucleotides in length, and polyadenylated. The P30 gene is single copy and contains no introns.
Guaiacol Hydrodeoxygenation over Platinum Catalyst: Reaction Pathways and Kinetics (2015)

Guaiacol represents a large fraction of lignin derived pyrolysis bio-oils. It was shown in our prior work that Pt has higher activity and stability for guaiacol hydrodeoxygenation as compared to other noble metal catalysts. In the present study, further theoretical and experimental investigations were conducted to reveal the reaction pathways and kinetics. For Pt/C catalyst in a fixed-bed reactor, the main liquid phase reaction products were phenol, catechol and cyclopentanone. Because cyclopentanone was typically not observed in the prior literature, a pathway for its formation was proposed and supported by density functional theory (DFT) calculations. By varying the space velocity, kinetic data was acquired in the temperature range 275 to 325 °C. The rate constants and activation energies for each subreaction in the network were obtained based on the power-law model.
Truncation artifact correction by support recovery (2013)

Truncation artifacts arise when the object being imaged extends past the scanned field of view (SFOV). The line integrals which lie beyond the SFOV are unmeasured, and reconstruction with traditional filtered backprojection (FBP) produces bright signal artifacts at the edge of the SFOV and little useful information outside the SFOV. A variety of techniques have been proposed to correct for truncation artifacts by estimating the unmeasured rays. We explore an alternative, iterative correction technique that reduces the artifacts and recovers the support (or outline) of the object that is consistent with the measured rays. We assume that the support is filled uniformly with tissue of a given CT number (for example, water-equivalent soft tissue) and segment the region outside the SFOV in a dichotomous fashion into tissue and air. In general, any choice for the object support will not be consistent with the measured rays in that a forward projection of the image containing the proposed support will not match the measured rays. The proposed algorithm reduces this inconsistency by deforming the object support to better match the measured rays. We initialize the reconstruction using the water cylinder extrapolation algorithm, an existing truncation artifact correction technique, but other starting algorithms can be used. The estimate of the object support is then iteratively deformed to reduce the inconsistency with the measured rays. After several iterations, forward projection is used to estimate the missing rays. Preliminary results indicate that this iterative, support recovery technique is able to produce superior reconstructions in the case of significant truncation compared to water cylinder extrapolation.
Stabilized Liner Implosions Driven by Axially-Moving Free-Pistons. (1977)

The use of axially-moving free-pistons to drive rotating liquid liners is described. The advantages of this approach include simple synchronism of piston motion to avoid low frequency Rayleigh-Taylor instability, a great reduction in the number of moving parts, and excellent azimuthal symmetry. Initial experimental results are presented which demonstrate stable, repetitive implosion-reexpansion cycles using a hydrodynamic scale-model. Further developments are also indicated. (Author)