gebhart/patrepeval huggingface dataset:
Identification of Trk binding sites for SHC and phosphatidylinositol 3'-kinase and formation of a multimeric signaling complex. (1993)

Phosphotyrosine-containing synthetic peptides were used to identify the binding sites for cellular polypeptides involved in nerve growth factor receptor/Trk-mediated signal transduction. In vitro association of SHC and the p85 subunit of phosphatidylinositol 3'-kinase with the Trk tyrosine kinase was prevented only by phosphorylated Y-490- and Y-751-containing peptides, respectively. In spite of the close proximity of the p85 binding site to that of phospholipase C gamma (Y-785), both target proteins are able to interact with the same receptor molecule simultaneously.
Three-Dimensional Numerical Simulations of Circular Cylinders Undergoing Two Degree-of-Freedom Vortex-Induced Vibrations (2006)

In an effort to gain a better understanding of vortex-induced vibrations (VIV), we present three-dimensional numerical simulations of VIV of circular cylinders. We consider operating conditions that correspond to a Reynolds number of 105, low structural mass and damping (m*=1.0, ζ*=0.005), a reduced velocity of U*=6.0, and allow for two degree-of-freedom (X and Y) motion. The numerical implementation makes use of overset (Chimera) grids, in a multiple block environment where the workload associated with the blocks is distributed among multiple processors working in parallel. The three-dimensional grid around the cylinder is allowed to undergo arbitrary motions with respect to fixed background grids, eliminating the need for grid regeneration as the structure moves on the fluid mesh.
774 Use of Formal Pharmacokinetic Analysis to Optimize Therapy in Patients With Secondary Loss of Response to Infliximab (2019)

INTRODUCTION: Infliximab (IFX) exhibits a wide range of inter-individual pharmacokinetic (PK) variability. During maintenance therapy, more than 50% of patients with inflammatory bowel disease have sub-optimal trough concentrations. In the 1 st year of IFX therapy, 40% experience a loss of response (LOR) due to non-immune mediated PK failure from suboptimal drug exposure. Currently, dose optimization relies on dose escalation or reduction by trial and error. Our aim was to formulate a model that maximizes the efficiency of IFX dose optimization using formal PK analysis. METHODS: We analyzed serum IFX levels obtained during the slow-decay portion of the drug concentration-versus-time curves of 30 normal volunteers that received a single standard dose (5 mg/kg) of IFX. 1 Using Prism (GraphPad Software, Seattle, WA), we determined the minimal number of serum IFX levels required to calculate the elimination rate constant (Kel). Volume of distribution (Vd) was determined by estimating blood volume. Peak drug concentration (Peak) was calculated by dividing IFX dose by Vd. Optimal dosing interval (T) was determined by the equation: T = ln (peak/trough) ÷ Kel. The equation was used to calculate T to achieve a specific trough concentration. IFX doses required to achieve a specific trough at a predetermined time interval was also calculated. RESULTS: Data for all patients is shown in Table 1. Five serum levels of IFX were required to accurately determine Kel. To maintain a trough &gt;5 µg/mL, calculated T ranged from 5.6 to 23.2 weeks. Calculated T was 7-9 weeks in 9 subjects, &lt;7 weeks in 11 subjects and &gt;9 weeks in 10 subjects. Conversely, optimum doses required to achieve a trough of ≥5 µg/mL with 8 week infusions ranged from 1.0 to 16.8 mg/kg (Table 2). Our model shows a direct relationship between administered doses and predicted troughs. There is a complex relationship between T and trough such that halving T usually showed a higher trough than a doubled dose (P &lt; 0.0001, Wilcoxon matched-pairs signed-ranks test) (Figure 1). CONCLUSION: Using a PK approach to adjust IFX therapy eliminates the requirement for multiple optimizations, and may reduce the need to switch to different drugs after failed optimizations. Our approach has the potential to reduce costs by decreasing IFX doses in some patients, prevention of premature discontinuation of IFX, and reducing the probability of LOR from low troughs in individual patients.
Lamellar projections in the endolymphatic sac act as a relief valve to regulate inner ear pressure (2018)

The inner ear is a fluid-filled closed-epithelial structure whose function requires maintenance of an internal hydrostatic pressure and fluid composition. The endolymphatic sac (ES) is a dead-end epithelial tube connected to the inner ear whose function is unclear. ES defects can cause distended ear tissue, a pathology often seen in hearing and balance disorders. Using live imaging of zebrafish larvae, we reveal that the ES undergoes cycles of slow pressure-driven inflation followed by rapid deflation. Absence of these cycles in <i>lmx1bb</i> mutants leads to distended ear tissue. Using serial-section electron microscopy and adaptive optics lattice light-sheet microscopy, we find a pressure relief valve in the ES comprised of partially separated apical junctions and dynamic overlapping basal lamellae that separate under pressure to release fluid. We propose that this lmx1-dependent pressure relief valve is required to maintain fluid homeostasis in the inner ear and other fluid-filled cavities.
Sporothriolide-Related Compounds from the Fungus Hypoxylon monticulosum CLL-205 Isolated from a Sphaerocladina Sponge from the Tahiti Coast (2017)

Two sporothriolide-related compounds were obtained from an extract of the fungus Hypoxylon monticulosum CLL-205, isolated from a Sphaerocladina sponge collected from the Tahiti coast. Compound 2 is a deoxy analogue of sporothric acid (4). Compound 3 is a newly reported unusual scaffold combining sporothriolide (1) and trienylfuranol A (5) moieties, through a Diels-Alderase-type reaction. Various experimental and analytical arguments supported the biocatalytic origin of compound 3. The structures of the isolated compounds were elucidated using 1D and 2D NMR, HRMS, and IR data. The structure and the absolute configuration of 3 were unambiguously confirmed by a single-crystal X-ray diffraction analysis.
Antitumor activity of paclitaxel-2'-glycinate conjugated to poly(ethylene glycol): a water-soluble prodrug. (1998)

Synthesis and in vivo antitumor activity evaluation of water-soluble poly(ethylene glycol) (PEG)-conjugated paclitaxel-2'-glycinate (6) are reported. This prodrug demonstrated enhanced antitumor activity and less toxicity in a P388/0 murine leukemia model when compared, on an equimolar basis, with native paclitaxel formulated in Cremophor/ethanol. Employing 6 in the treatment of HT-29, A549 and SKOV3 solid tumor-bearing xenografted mice demonstrated significant antitumor activity. The outstanding performance of 6 may be attributed partly to the tripartate nature of the prodrug.
From Pro-nucleotides to Pro-oligonucleotides (1995)

Abstract Consequences of masking the phosphate functions of nucleic acid derivatives by enzyme labile bioreversible protecting groups are discussed.
Fatal Crashes of Female Drivers Wearing Safety Belts (1996)

&lt;div class="htmlview paragraph"&gt;Fatal crash circumstances for 48 belted female drivers were studied in-depth and compared to those of 83 belted male drivers in a similar population of vehicles. Women had a higher incidence of crashes on slippery roads, during lane changes and passing maneuvers than men who had a higher rate of aggressive driving and speed related crashes (χ&lt;sup&gt;2&lt;/sup&gt; = 10.47, p &amp;lt; 0.001). Driver-side damage was significantly more frequent in female than male crashes (χ&lt;sup&gt;2&lt;/sup&gt; = 5.74, p &amp;lt; 0.025) and women had a higher fraction of side impacts (45.9% v 31.4%) and crashes during daylight (87.0% v 72.3%, χ&lt;sup&gt;2&lt;/sup&gt; = 3.65, p &amp;lt; 0.05) than men. Women also had a higher fraction of potentially avoidable crashes than men (57.5% v 39.0%) and a lower involvement related to aggressive driving (10.6% v 25.6%). These differences were statistically significant (χ&lt;sup&gt;2&lt;/sup&gt; = 5.41, p &amp;lt; 0.025). Thirty percent of the avoidable fatal crashes of women occurred on slippery roads where the driver's reaction and experience in handling a vehicle in an emergency may be a factor.&lt;/div&gt;
Comparison of 2-amino-[3- 11C]isobutyric acid and 2-deoxy-2-[18F]fluoro-D-glucose in nude mice with xenografted tumors and acute inflammation (2012)

[3-11C]AIB accumulates more selectively in tumor tissue than does [18F]FDG and thus has the potential of discriminating between tumors and inflammatory lesions better and of complementing the limitation of [18F]FDG.
Absence of WASp Enhances Hematopoietic and Megakaryocytic Differentiation in a Human Embryonic Stem Cell Model (2015)

The Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency caused by mutations in the WAS gene and characterized by severe thrombocytopenia. Although the role of WASp in terminally differentiated lymphocytes and myeloid cells is well characterized, its role in early hematopoietic differentiation and in platelets (Plts) biology is poorly understood. In the present manuscript, we have used zinc finger nucleases targeted to the WAS locus for the development of two isogenic WAS knockout (WASKO) human embryonic stem cell lines (hESCs). Upon hematopoietic differentiation, hESCs-WASKO generated increased ratios of CD34(+)CD45(+) progenitors with altered responses to stem cell factor compared to hESCs-WT. When differentiated toward the megakaryocytic linage, hESCs-WASKO produced increased numbers of CD34(+)CD41(+) progenitors, megakaryocytes (MKs), and Plts. hESCs-WASKO-derived MKs and Plts showed altered phenotype as well as defective responses to agonist, mimicking WAS patients MKs and Plts defects. Interestingly, the defects were more evident in WASp-deficient MKs than in WASp-deficient Plts. Importantly, ectopic WAS expression using lentiviral vectors restored normal Plts development and MKs responses. These data validate the AND-1_WASKO cell lines as a human cellular model for basic research and for preclinical studies for WAS.
Morphological behavior of A2B2 star block copolymers (1999)

A series of A2B2 four-arm, miktoarm stars of polystyrene and polyisoprene have been synthesized. The morphological behavior of these materials has been characterized using TEM, SAXS, and SANS, and was found to agree in general with the predictions of Milner's theory for miktoarm star morphological behavior. One sample was found to exhibit a cylindrical morphology where lamellae were predicted; this behavior is similar to other discrepancies observed in previous studies of miktoarm star morphological behavior. A second sample, predicted to form a bicontinuous morphology, was found to exhibit hexagonally packed cylinders. The tetrafunctional junction point also results in an increase in spacing for the lamellar sample in this series over that of an AB diblock, but not as great as the increase previously observed for A8B8 16-arm star materials. © 1999 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 37: 3392–3400, 1999
Supplementary Figures 1-4 from Preclinical Pharmacology, Antitumor Activity, and Development of Pharmacodynamic Markers for the Novel, Potent AKT Inhibitor CCT128930 (2023)

Supplementary Figures 1-4 from Preclinical Pharmacology, Antitumor Activity, and Development of Pharmacodynamic Markers for the Novel, Potent AKT Inhibitor CCT128930
<title>Active flexure compensation software for the echellette spectrograph and imager on Keck II</title> (2000)

All Cassegrain spectrographs suffer from gravitationally- induced flexure to some degree. While such flexure can be minimized via careful attention to mechanical design and fabrication, further performance improvements can be achieved if the spectrograph has been designed to minimize hysteresis and has active compensation for any residual flexure. The Echellette Spectrograph and Imager (ESI), built at UCO/Lick Observatory for use at Cassegrain focus on Keck II, compensates for such residual flexure via its collimator mirror. The collimator is driven by three actuators that provide control of collimator focus, tip, and tilt. The ESI control software utilizes a mathematical model of gravitationally-induced flexure to periodically compute and apply flexure corrections by commanding the corresponding tip and tilt motions to the collimator. In addition, the ESI control software provides an optional, manual, closed-loop method for adjusting the collimator position to compensate for any non-repeatable errors. Such errors may result from mechanical hysteresis or from thermally-induced structural deformations of the instrument and are thus not accounted for by the gravitational flexure model. This method relies on measuring the centroid position of fiducial spots within each echellete image. The collimator is adjusted so that the positions of these spots match those in a reference image. These spots are produced by a small round hole in the slit mask located near one end of the slit. We discuss the design and calibration of this flexure compensation system and report on its performance ont he telescope.
Hydroamination of Phenylacetylene with Aniline over Gold Nanoparticles Embedded in the Boron Imidazolate Framework BIF-66 and Zeolitic Imidazolate Framework ZIF-67 (2021)

The hydroamination of alkynes is an atom-economy process in the organic synthesis for the C-N bond formation, thereby allowing the production of fine chemicals and intermediates. However, direct interaction between alkynes and amines is complicated due to the electron enrichment of both compounds. Therefore, efficient hydroamination catalysts, especially heterogeneous ones, are in great demand. This work aimed at the development of novel heterogeneous catalysts based on zeolite-like metal-organic frameworks for phenylacetylene hydroamination. The sodalite (SOD) type zeolitic imidazolate framework ZIF-67 (Co(meim)<sub>2</sub>, meim = 2-methylimidazolate) and boron imidazolate framework BIF-66 ({Co[B(im)<sub>4</sub>]<sub>2</sub>}<sub>n</sub>, im = imidazolate) were studied as the carriers for the gold nanoparticles (Au-NPs). Au-NPs were embedded in the ZIF-67 and BIF-66 matrices by incipient wetness impregnation. Au@ZIF-67 and Au@BIF-66 hybrids were studied for the first time in the liquid phase hydroamination of phenylacetylene with aniline in an air atmosphere and have shown high activity and selectivity in respect to imine in this process. The pronounced impact of the nature of the metal-organic carrier, Au source, and reducing agent on the catalytic performance of the synthesized nanomaterials was found. To the best of our knowledge, it is the first example of using the zeolitic imidazolate framework and boron-imidazolate framework as the components of the gold-containing catalytic systems for the alkyne hydroamination.
Efficient octave-spanning frequency comb generation in normal dispersion regime (2018)

In this paper, we present a stable dark soliton with its spectrum spanning about one octave generated in the silicon nitride microring resonator with normal dispersion. The dark soliton can be generated straightforwardly from noise. Then, we investigate the dependence of bandwidth and power level on pump power, the second-order dispersion, the ratio of coupling and intracavity loss coefficient and free spectral range.
Binary decomposable codes over N×N-PSK constellations (2002)

A new class of group codes suitable for N/spl times/M-PSK constellations is introduced. We describe a low complexity bounded distance decoding algorithm and a simple implementation of a differential encoder for these codes. Furthermore some relations for the evaluation of their performance are derived.
Invited Paper: Lessons from HotStuff (2023)

This article will take you on a journey to the core of blockchains, their Byzantine consensus engine, where HotStuff emerged as a new algorithmic foundation for the classical Byzantine generals consensus problem. The first part of the article underscores the theoretical advances HotStuff enabled, including several models in which HotStuff-based solutions closed problems which were opened for decades. The second part focuses on HotStuff performance in real life setting, where its simplicity drove adoption of HotStuff as the golden standard for blockchain design, and many variants and improvements built on top of it. Both parts of this document are meant to describe lessons drawn from HotStuff as well as dispel certain myths.
Advanced techniques for lithologic and fracture analysis utilizing thematic mapper and topographic data (1985)

Under the LIDQA program, the Pacific Northwest Laboratory has been evaluating selected energy-related applications of the Landsat Thematic Mapper (TM) data from a user-agency perspective. This paper describes techniques that have been developed to correct for topographic-induced shading on TM surface relfectance and to perform topographic analysis to define crustal fracture zones as aids to geologic studies. These techniques require the use of only digital terrain and TM data. The analysis techniques have been successfully applied to the Paiute Ridge Quadrangle in Nevada, demonstrating the utility of the techniques for geologic studies. 13 refs., 4 figs.
Evaluation of the potent anti-hepatitis B virus agent (-) cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine in a novel in vivo model (1994)

A murine model was developed to investigate the in vivo activity of anti-hepatitis B virus (HBV) agents. Mice with subcutaneous tumors of HBV-producing 2.2.15 cells showed reductions in levels of HBV in serum and in intracellular levels of HBV when the mice were orally dosed with (-) cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine (FTC). No effects on tumor size or alpha-fetoprotein levels were observed. FTC can selectively inhibit HBV replication at nontoxic doses.
Data from Amplification of Oncolytic Vaccinia Virus Widespread Tumor Cell Killing by Sunitinib through Multiple Mechanisms (2023)

&lt;div&gt;Abstract&lt;p&gt;Oncolytic viruses pose many questions in their use in cancer therapy. In this study, we assessed the potential of mpJX-594 (mouse-prototype JX-594), a replication-competent vaccinia virus administered by intravenous injection, to target the tumor vasculature, produce immune activation and tumor cell killing more widespread than the infection, and suppress invasion and metastasis. These actions were examined in RIP-Tag2 transgenic mice with pancreatic neuroendocrine tumors that developed spontaneously and progressed as in humans. mpJX-594 initially infected tumor vascular endothelial cells, leading to vascular pruning and prolonged leakage in tumors but not in normal organs; parallel effects were observed in U87 gliomas. Viral infection spread to tumor cells, where tumor cell killing was much more widespread than the infection. Widespread tumor cell killing at 5 days was prevented by depletion of CD8&lt;sup&gt;+&lt;/sup&gt; T lymphocytes and did not require GM-CSF, as mpJX-594 variants that expressed human, mouse, or no GM-CSF produced equivalent amounts of killing. The antivascular, antitumor, and antimetastatic effects of mpJX-594 were amplified by concurrent or sequential administration of sunitinib, a multitargeted receptor tyrosine kinase inhibitor. These effects were not mimicked by selective inhibition of VEGFR2 despite equivalent vascular pruning, but were accompanied by suppression of regulatory T cells and greater influx of activated CD8&lt;sup&gt;+&lt;/sup&gt; T cells. Together, our results showed that mpJX-594 targets tumor blood vessels, spreads secondarily to tumor cells, and produces widespread CD8&lt;sup&gt;+&lt;/sup&gt; T-cell–dependent tumor cell killing in primary tumors and metastases, and that these effects can be amplified by coadministration of sunitinib.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Significance:&lt;/b&gt; These findings reveal multiple unrecognized features of the antitumor properties of oncolytic vaccinia viruses, all of which can be amplified by the multitargeted kinase inhibitor sunitinib. &lt;i&gt;Cancer Res; 78(4); 922–37. ©2017 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Abstract 2403: Biopsy-free comprehensive tumor profiling of 1,000+ consecutive cancer patients using CLIA-certified commercial test and its clinical utility (2015)

Abstract Background: Genomic alterations of metastatic cancers may be discordant with alterations in primary tumors due to continuous evolution of disease and tumor heterogeneity. Current NGS approaches based on tissue biopsies can fail to capture a complete picture of the real-time cancer profile. Biopsy-free genomic profiling of circulating tumor DNA (ctDNA) can provide deep insights into the disease when biopsies are not an option. Methods: We developed Guardant360 for comprehensive profiling of ctDNA with high sensitivity (detection in 90%+ of advanced cancer pts) and ultra-high specificity (&amp;gt;99.9999%). Guardant360 has been validated to analyze a 69-oncogene panel covering over 120,000 bases and detects SNVs, gene amplifications, indels and genomic rearrangements, including all NCCN-guidelines recommended biomarkers. We previously reported high concordance of ctDNA profiles with concurrent matched biopsies. Results: In our first 1,000 clinical tests (77% across breast, colorectal and lung and 23% distributed over many other indications), we successfully processed 99.8% of samples. In 3 cases, we canceled the test as we detected secondary genome carry-over (confirmed to be pregnancy or liver transplant cases). Despite the wider range of clinical stages in commercial samples, we detected ctDNA in 78%. Additionally, we identified actionable mutations with associated treatments in 74% of those cases. Clinical benefit of the test was shown in many patients. Examples: A refractory IBC patient with Her2 status change, showed strong response to Her2 TKI. Patients with quantity-not-sufficient biopsy sequencing, showed strong actionable alterations (ERBB2 amplification, BRAF mutation, EGFR activating and resistance mutations, etc) Conclusion: Comprehensive sequencing of a patient's cancer in real -time through a simple blood test can empower oncologists to make better informed treatment decisions, especially when repeat tissue biopsy is not a desirable or viable option. Citation Format: Eric Collisson, Stefanie Mortimer, Dragan Sebisanovic, Reza Mokhtari, Somayeh Bakhtiari, Rene Lopez, Devi M. Gadde, Maria M. Vidamo, Heena Patel, Bahram G. Kermani, Helmy Eltoukhy, Richard B. Lanman, AmirAli Talasaz. Biopsy-free comprehensive tumor profiling of 1,000+ consecutive cancer patients using CLIA-certified commercial test and its clinical utility. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2403. doi:10.1158/1538-7445.AM2015-2403
Thin‐Film PECVD (AKT) (2018)

Plasma-enhanced chemical vapor deposition (PECVD) method is widely used for thin-film deposition of insulating and semiconducting layers in thin-film transistors (TFT) for active-matrix liquid-crystal display (AMLCD) and active-matrix organic light-emitting diode (AMOLED) displays. The basic guideline for scaling up PECVD processes generation to generation has been to maintain the same intensive deposition parameters, such as substrate temperature, deposition pressure, and electrode spacing, while somewhat proportionally increasing the extensive deposition parameters such as radio frequency (RF) power and gas flow rate. All modern PECVD chambers are also equipped with in situ dry cleaning capability in the form of a remote plasma source cleaning (RPSC) unit. RPSC technology created a second productivity revolution in mass production PECVD tools due to further improvements in particles and yield performance, as well as enabling a longer lifetime of process chamber components such as diffusers and susceptors.