gebhart/patrepeval huggingface dataset:
Mass spectrometry and combinatorial chemistry: a short outline (2001)

The rapid evolution of combinatorial chemistry in recent years has led to a dramatic improvement in synthetic capabilities. The goal is to accelerate the discovery of molecules showing affinity against a target, such as an enzyme or a receptor, through the simultaneous synthesis of a great number of structurally diverse compounds. This is done by generating combinatorial libraries containing as many as hundreds or thousands of compounds. The need to test all these compounds led to the development of high-throughput screening (HTS) techniques, and also high-throughput analytical techniques capable of assessing the occurrence, structure and purity of the products. In order to be applied effectively to the characterization of combinatorial libraries, an analytical technique must be adequately sensitive (to analyse samples which are typically produced in nanomole amounts or less), fast, affordable and easy to automate (to minimize analysis time and operator intervention). Although no method alone can meet all the analytical challenges underlying this task, the recent progress in mass spectrometric (MS) instrumentation renders this technique an essential tool for scientists working in this area. We describe here relevant aspects of the use of MS in combinatorial technologies, such as current methods of characterization, purification and screening of libraries. Some examples from our laboratory deal with the analysis of pooled oligomeric libraries containing n x 324(n = 1, 2) compounds, using both on-line high-performance liquid chromatography/MS with an ion trap mass spectrometer, and direct infusion into a triple quadrupole instrument. In the first approach, MS and product ion MS/MS with automatic selection of the precursor were performed in one run, allowing library confirmation and structural elucidation of unexpected by-products. The second approach used MS scans to characterize the entire library and also precursor ion and neutral loss scans to detect selectively components with given structural characteristics.
Wafer scale fabrication of silicon nitride MEMS phase shifters with XeF2 dry vapor release etch process (2022)

Integrated photonic systems require reliable, low power consumption phase shifters in order to scale circuit complexity. Micro-electromechanical systems (MEMS) are a viable candidate to provide low-power phase shifting, without the significant drawbacks of thermo-optic effects (high power usage and cross-talk). Previous works have demonstrated MEMS phase tuning through vertically displaced microbridges. However, these require &gt; 40 V for a π phase shift [1] using gradient electric fields, though lower voltage requirements have been demonstrated for direct electrostatic actuation [2]. Ultra-low voltage (∼ 1 V) designs using horizontal slot waveguides have recently been demonstrated [3–5] although these methods require complex mechanical structures that must be released using vapor-<i>HF</i> or critical point drying post-processing. Here we present low-voltage phase tuning of vertically actuated beams that are released at wafer level with a vapor <i>XeF</i><sub>2</sub> etch completely in-house. Our process is carried out on an i-line photolithography stepper to define the waveguiding, metal, and MEMS structures. We use a sacrificial polysilicon layer between the SiN waveguide and the SiN beam. The <i>XeF</i><sub>2</sub> undercuts the beam, enabling a simple MEMS release process that does not undercut the waveguide. The movable SiN beam on top of the waveguide utilizes a single-sided anchor so that it resembles a wide and short single-clamped cantilever. This enables a phase shifter that is capable of a π phase shift with &lt; 10 V and length &lt; 100 <i>μ</i>m. We measure the optical transmission versus applied voltage for multiple voltage sweeps and extract the phase shift per voltage at various wavelengths. We demonstrate reliable tuning over multiple sweeps with an average voltage of 7 V ± 0.5 V for a π phase shift. This phase shifter is central to the scalability of programmable photonic circuits, including quantum photonics.
Radial Index Tailoring for Reduced Intermodal Coupling in Large-Mode-Area Fiber Lasers and Amplifiers (2007)

Low-order Gaussian index profiles result in increased modal index contrast. Intermodal coupling can be reduced by a factor of 10 to 100, with nonlinear thresholds increased by a factor of 3 to 7 due to larger effective areas.
HIP-based RFID Networking Architecture (2007)

Digital Object Identifier 10.1109/WOCN.2007.4284140
Solid State Fluorination on the Minute Scale: Synthesis of WO3−xFx with Photocatalytic Activity (2020)

Abstract Solid state reactions are notoriously slow, because the rate‐limiting step is diffusion of atoms or ions through reactant, intermediate, and product crystalline phases. This requires days or even weeks of high temperature treatment, consuming large amounts of energy. Metal oxides are particularly difficult to react, because they have high melting points. The study reports a high‐speed solid state fluorination of WO 3 with Teflon to the oxyfluorides WO 3– x F x on a minute (&lt;10 min) scale by spark plasma sintering, a technique that is used typically for a high‐speed consolidation of powders. Automated electron diffraction analysis reveals an orthorhombic ReO 3 ‐type structure of WO 3– x F x with F atom disorder as demonstrated by 19 F magic angle spinning nuclear magnetic resonance spectroscopy. The potential of this new approach is demonstrated by the following results. i) Mixed‐ valent tungsten oxide fluorides WO 3– x F x with high F content (0 &lt; x &lt; 0.65) are obtained as metastable products in copious amounts within minutes. ii) The spark plasma sintering technique yields WO 3– x F x nanoparticles with high photocatalytic activity, whereas the corresponding bulk phases obtained by conventional solid‐state (ampoule) reactions have no photocatalytic activity. iii) The catalytic activity is caused by the microstructure originating from the processing by spark plasma sintering.
TopicPanorama: A Full Picture of Relevant Topics (2016)

This paper presents a visual analytics approach to analyzing a full picture of relevant topics discussed in multiple sources, such as news, blogs, or micro-blogs. The full picture consists of a number of common topics covered by multiple sources, as well as distinctive topics from each source. Our approach models each textual corpus as a topic graph. These graphs are then matched using a consistent graph matching method. Next, we develop a level-of-detail (LOD) visualization that balances both readability and stability. Accordingly, the resulting visualization enhances the ability of users to understand and analyze the matched graph from multiple perspectives. By incorporating metric learning and feature selection into the graph matching algorithm, we allow users to interactively modify the graph matching result based on their information needs. We have applied our approach to various types of data, including news articles, tweets, and blog data. Quantitative evaluation and real-world case studies demonstrate the promise of our approach, especially in support of examining a topic-graph-based full picture at different levels of detail.
High power, 60MHz, cryogenically cooled, mode-locked, Yb:YAG oscillator (2011)

We demonstrate a 60MHz, cryogenically cooled, mode-locked Yb:YAG oscillator with up to 12W average output power. Mode-locking is achieved via a SESAM, an intracavity SHG crystal, and an iris near focus for spatial mode filtering.
GeoMol: Torsional Geometric Generation of Molecular 3D Conformer Ensembles (2021)

Prediction of a molecule's 3D conformer ensemble from the molecular graph holds a key role in areas of cheminformatics and drug discovery. Existing generative models have several drawbacks including lack of modeling important molecular geometry elements (e.g. torsion angles), separate optimization stages prone to error accumulation, and the need for structure fine-tuning based on approximate classical force-fields or computationally expensive methods such as metadynamics with approximate quantum mechanics calculations at each geometry. We propose GeoMol--an end-to-end, non-autoregressive and SE(3)-invariant machine learning approach to generate distributions of low-energy molecular 3D conformers. Leveraging the power of message passing neural networks (MPNNs) to capture local and global graph information, we predict local atomic 3D structures and torsion angles, avoiding unnecessary over-parameterization of the geometric degrees of freedom (e.g. one angle per non-terminal bond). Such local predictions suffice both for the training loss computation, as well as for the full deterministic conformer assembly (at test time). We devise a non-adversarial optimal transport based loss function to promote diverse conformer generation. GeoMol predominantly outperforms popular open-source, commercial, or state-of-the-art machine learning (ML) models, while achieving significant speed-ups. We expect such differentiable 3D structure generators to significantly impact molecular modeling and related applications.
ChemInform Abstract: NICHTKLASSISCHE KONDENSIERTE THIOPHENE 2. MITT. TETRAPHENYLTHIENO(3,4‐C)THIOPHEN (1973)

Abstract Die Titelverbindung (IV) wird ausgehend vorn Tetrabenzoyläthan (I) dargestellt, dessen Reaktion mit P‐pentasulfid ein Gemisch zweier Isomeren liefert, aus dem das überwiegend gebildete cis‐Isomere (II) isoliert und oxidiert wird.
A Monoclonal Antibody Combination against both Serotypes A and B Botulinum Toxin Prevents Inhalational Botulism in a Guinea Pig Model (2021)

Botulinum neurotoxins (BoNT) are extremely potent and can induce respiratory failure, requiring long-term intensive care to prevent death. Recombinant monoclonal antibodies (mAbs) hold considerable promise as BoNT therapeutics and prophylactics. In contrast, equine antitoxin cannot be used prophylactically and has a short half-life. Two three-mAb combinations are in development that specifically neutralize BoNT serotype A (BoNT/A) and B (BoNT/B). The three-mAb combinations addressing a single serotype provided pre-exposure prophylaxis in the guinea pig inhalation model. A lyophilized co-formulation of six mAbs, designated G03-52-01, that addresses both A and B serotypes is in development. Here, we investigated the efficacy of G03-52-01 to protect guinea pigs against an aerosol exposure challenge of BoNT/A1 or BoNT/B1. Previously, it was found that each antibody demonstrated a dose-dependent exposure and reached maximum circulating concentrations within 48 h after intramuscular (IM) or intravenous (IV) injection. Here we show that G03-52-01, in a single IM injection of G03-52-01 administered 48 h pre-exposure, protected guinea pigs against an aerosol challenge of up to 238 LD<sub>50</sub>s of BoNT/A1 and 191 LD<sub>50</sub>s of BoNT/B1. These data suggest that a single IM administration of G03-52-01 provides pre-exposure prophylaxis against botulism from an aerosol exposure of BoNT/A1 or BoNT/B1.
Electrospray mass spectra of protein cations formed in basic solutions (1994)

Abstract The electrospray mass spectra of gramicidin S cations that originated from 0.2 M solutions of 18 nitrogen‐containing bases were examined. The relative abundances of the [M + 2H] 2+ to the [M + H] + ion were found to correlate not with the solution pH but with the proton affinities of the bases. It is postulated that some of the [M + 2H] 2+ and the [M + H] + ions exist as adducts with the nitrogen bases in solution, these adducts being desorbed into the gas phase during electrospray and dissociated in the lens region via collision‐induced dissociations to yield apparent proton attachment spectra. Some of these adducts were observed under nominally zero collision energy conditions.
Modeling and transport simulations of F - theta pumping in the RFP (1986)

The necessity of m=1 modes for current drive has been shown in cylindrical geometry by using Faraday's and Ohm's laws and regularity conditions on the magnetic axis. An m=1 tearing mode that generates poloidal flux (necessary for current drive) has been identified in the form of an unstable off-axis parallel current peak. A 1-D analytical model based on the Kadomtsev reconnection model has been developed to describe the effects of this instability. A scoping of the F - theta space has been performed using a polynomial expansion for the parallel current profile, a linear resistive stability code and the 1-D reconnection model to find where this mode is unstable, the relative increase of poloidal flux and the size of the reconnecting region. A comparison between 1-D plasma transport simulations and the results from the F - theta pumping experiment, currently under way on ZT-40M at Los Alamos, will be presented.
Dextrose solution for priming and rinsing the extracorporeal circuit in hemodialysis patients: A prospective pilot study (2021)

Identifier NCT01168947 (ClinicalTrials.gov).
Abstract 4681: Inhibition of poly (ADP-ribose) polymerase-1 (PARP-1) as a strategy for targeted therapy in Ewing's sarcoma (2012)

Abstract The Ewing's sarcoma family of tumors (ESFTs) are aggressive malignancies which frequently harbor EWS-FLI1 or EWS-ERG genomic fusions. Here, we demonstrate that these fusion products interact with, and depend on, poly (ADP-ribose) polymerase 1 (PARP1), a DNA damage response protein and transcriptional co-regulator. This interaction occurs in a DNA-independent manner. ESFT cell lines and xenografts are preferentially sensitive to PARP1 inhibition, and the addition of a PARP1 inhibitor to the second-line chemotherapeutic agent temozolamide resulted in complete response of all treated tumors in an EWS-FLI1 ESFT xenograft model. PARP inhibition blocked Ewing's cell line, but not control osteosarcoma or rhabdomyosarcoma cell line invasion, as well as the formation of lung metastasis in a xenograft model of ESFT. Mechanistically, the EWS-FLI1 and EWS-ERG fusions induce DNA damage, which is potentiated by PARP1 inhibition in ESFT cell lines. In a positive feedback loop, EWS-FLI1 fusions maintain the expression of PARP1 by direct regulation of the PARP1 promoter. This regulation is independently supported by a gene expression array data set of 20 ESFT patient tumors (Spearman r = 0.8165). Finally, because front-line therapy for this disease includes an intense regimen of five cytotoxic chemotherapy agents from which patients can quickly relapse with even more aggressive disease, we studied the effect of PARP inhibition in two Ewing's sarcoma cell line models derived after patient relapse. Importantly, these two cell lines maintained a preferential sensitivity to PARP1 inhibition despite their general chemoresistance. These findings suggest that targeting the EWS-FLI1: PARP1 interaction axis is a promising therapeutic strategy for the Ewing's sarcoma family of tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4681. doi:1538-7445.AM2012-4681
PGE2-mediated podosome loss in dendritic cells is dependent on actomyosin contraction downstream of the RhoA–Rho-kinase axis (2008)

Podosomes are dynamic adhesion structures found in dendritic cells (DCs) and other cells of the myeloid lineage. We previously showed that prostaglandin E2 (PGE2), an important proinflammatory mediator produced during DC maturation, induces podosome disassembly within minutes after stimulation. Here, we demonstrate that this response is mediated by cAMP elevation, occurs downstream of Rho kinase and is dependent on myosin II. Whereas PGE2 stimulation leads to activation of the small GTPase RhoA, decreased levels of Rac1-GTP and Cdc42-GTP are observed. These results show that PGE2 stimulation leads to activation of the RhoA-Rho-kinase axis to promote actomyosin-based contraction and subsequent podosome dissolution. Because podosome disassembly is accompanied by de novo formation of focal adhesions, we propose that the disassembly/formation of these two different adhesion structures is oppositely regulated by actomyosin contractility and relative activities of RhoA, Rac1 and Cdc42.
Progression of coronary artery disease in young male post-infarction patients is linked to disturbances of carbohydrate and lipoprotein metabolism and to impaired fibrinolytic function (1998)

Disturbances in carbohydrate and lipoprotein metabolism and impaired fibrinolytic function are associated with progression of coronary artery disease in young male post-infarction patients.
EncapsulatedStreptococcus suisInhibits Activation of Signaling Pathways Involved in Phagocytosis (2004)

Streptococcus suis capsular type 2 is an important zoonotic agent of meningitis. Previous studies reported that, in contrast to nonencapsulated mutants, encapsulated S. suis is able to resist phagocytosis. However, the mechanisms by which S. suis avoids phagocytosis are unknown. To elucidate the signaling pathway(s) involved in S. suis antiphagocytosis, we compared the ability of an encapsulated strain and its nonencapsulated mutant to induce the activation of Akt and protein kinase C (PKC), which are downstream kinases of the phosphatidylinositol 3-kinase (PI-3K) pathway, known to be involved in the phagocytosis processes. The results demonstrated high levels of Akt and PKCalpha phosphorylation after infection of J774 macrophages with the nonencapsulated mutant, whereas the encapsulated strain showed reduced activation of PI-3K/Akt/PKCalpha signaling pathway, as well as several protein tyrosine events. These results correlated with the number of intracellular bacteria. Macrophages pretreated with specific PI-3K or PKC inhibitors showed reduced levels of Akt and PKCalpha phosphorylation, resulting in 50% reduction of phagocytosis. The role of phosphatases in the antiphagocytic mechanisms was evaluated by using phosphatase inhibitors, as well as SHP-1-deficient macrophages. Only in the absence of SHP-1 did the phagocytosis of encapsulated S. suis significantly increase, leading to Akt phosphorylation levels similar to those observed with the nonencapsulated strain, indicating activation of this important SH2 domain-containing tyrosine phosphatase by encapsulated S. suis. Finally, when purified S. suis capsular polysaccharide (CPS) was added to macrophages, no phosphorylation events were observed. In addition, CPS and encapsulated S. suis were able to inhibit the uptake of the nonencapsulated mutant. These results suggest the importance of CPS in the mechanisms, whereby S. suis downmodulates phagocytosis.
Adhesion of spray droplets to foliage: The role of dynamic surface tension and advantages of organosilicone surfactants (1993)

Abstract Measurements of the dynamic surface tension of seven surfactants (four organosilicones, two ‚conventional’︁ hydrocarbon‐based surfactants and an organosilicone + hydrocarbon‐based blend; 0.5 to 5.0 g litre −1 ) have been combined with data on the adhesion of their spray droplets to pea leaf. The latter were determined by a method enabling the surface age, and thus surface tension of the droplets at impact, to be calculated. Adhesion was directly related to the dynamic reduction in surface tension (2 to 50 mN m −1 ) prior to impact. The organosilicone surfactants and the blend reduced surface tension more rapidly and to lower values than did the organic surfactants. Adhesion was also inversely related to droplet size (110 to 880 μm diameter), droplet velocity (0.3 to 2.8 m s −1 ) and angle of incidence on the leaf (0 to 67.5 degrees). These physical factors were of less importance than surface tension in controlling adhesion. Relative adhesion varied among the surfactants both with their concentration and with surface tension. These findings are discussed with respect to their implications for the possible involvement of surface viscosity in the spray impaction process.
Aminoglycoside uptake and mode of action—with special reference to streptomycin and gentamicin (1981)

Journal Article Aminoglycoside uptake and mode of action—with special reference to streptomycin and gentamicin: II. Effects of aminoglycosides on cells Get access Robert E. W. Hancock Robert E. W. Hancock Department of Microbiology, University of British ColumbiaVancouver, B.C., Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Antimicrobial Chemotherapy, Volume 8, Issue 6, December 1981, Pages 429–445, https://doi.org/10.1093/jac/8.6.429 Published: 01 December 1981
Prevention of influenza by targeting host receptors using engineered proteins (2014)

There is a need for new approaches for the control of influenza given the burden caused by annual seasonal outbreaks, the emergence of viruses with pandemic potential, and the development of resistance to current antiviral drugs. We show that multivalent biologics, engineered using carbohydrate-binding modules specific for sialic acid, mask the cell-surface receptor recognized by the influenza virus and protect mice from a lethal challenge with 2009 pandemic H1N1 influenza virus. The most promising biologic protects mice when given as a single 1-μg intranasal dose 7 d in advance of viral challenge. There also is sufficient virus replication to establish an immune response, potentially protecting the animal from future exposure to the virus. Furthermore, the biologics appear to stimulate inflammatory mediators, and this stimulation may contribute to their protective ability. Our results suggest that this host-targeted approach could provide a front-line prophylactic that has the potential to protect against any current and future influenza virus and possibly against other respiratory pathogens that use sialic acid as a receptor.
Enhanced Air Stability of Polymer Solar Cells with a Nanofibril-Based Photoactive Layer (2014)

In spite of the rapid increase in the power conversion efficiency (PCE) of polymer solar cells (PSCs), the poor stability of the photoactive layer in air under sunlight is a critical problem blocking commercialization of PSCs. This study investigates the photo-oxidation behavior of a bulk-heterojunction (BHJ) photoactive film made of single-crystalline poly(3-hexlythiophene) (P3HT) nanofibrils and fullerene derivatives [phenyl-C61-butyric methyl ester (PCBM), indene-C 60 bisadduct (ICBA)]. Because the single-crystalline P3HT nanofibrils had tightly packed π-π stacking, the permeation of oxygen and water into the nanofibrils was significantly reduced. Chemical changes in P3HT were not apparent in the nanofibrils, and hence the air stability of the nanofibril-based BHJ film was considerably enhanced as compared with conventional BHJ films. The chemical changes were monitored by Fourier-transform infrared (FT-IR) spectroscopy, Raman spectroscopy, and UV-vis absorbance. Inverted PSCs made of the nanofibril-based BHJ layer also showed significantly enhanced air stability under sunlight. The nanofibril-based solar cell maintained more than 80% of its initial PCE after 30 days of continuous exposure to sunlight (AM 1.5G, 100 mW/cm(2)), whereas the PCE of the conventional BHJ solar cell decreased to 20% of its initial PCE under the same experimental conditions.
MAPkinaseQuest: novel roadway to αIIbβ3 activation (2006)

Comment on Li et al, page [965][1]

In this issue, Li and colleagues delineate a novel signaling pathway, in which 2 MAPK kinases are shown to regulate the activation of integrin αIIbβ3 on platelets.

Platelet stimulation begins with the binding of agonists, such as thrombin and von Willebrand