gebhart/patrepeval huggingface dataset:
Receptor-Driven ERK Pulses Reconfigure MAPK Signaling and Enable Persistence of Drug-Adapted BRAF-Mutant Melanoma Cells (2020)

Targeted inhibition of oncogenic pathways can be highly effective in halting the rapid growth of tumors but often leads to the emergence of slowly dividing persister cells, which constitute a reservoir for the selection of drug-resistant clones. In BRAF<sup>V600E</sup> melanomas, RAF and MEK inhibitors efficiently block oncogenic signaling, but persister cells emerge. Here, we show that persister cells escape drug-induced cell-cycle arrest via brief, sporadic ERK pulses generated by transmembrane receptors and growth factors operating in an autocrine/paracrine manner. Quantitative proteomics and computational modeling show that ERK pulsing is enabled by rewiring of mitogen-activated protein kinase (MAPK) signaling: from an oncogenic BRAF<sup>V600E</sup> monomer-driven configuration that is drug sensitive to a receptor-driven configuration that involves Ras-GTP and RAF dimers and is highly resistant to RAF and MEK inhibitors. Altogether, this work shows that pulsatile MAPK activation by factors in the microenvironment generates a persistent population of melanoma cells that rewires MAPK signaling to sustain non-genetic drug resistance.
[Nanosystems and targeted transport of medicinal preparations to the brain]. (2009)

Intense efforts in the last decades have resulted in numerous inventions to improve drug delivery to CNS. Some of them have significant potential for clinical applications. At the same time, the variety of these strategies is in itself indicative of great difficulties inherent in the transfer of therapeutic and imaging agents across the blood-brain barrier. Combination of several approaches, such as encapsulation of drugs in nanocontainers, incorporation in micellar nanostructures, the use of Pluronic "unimers" for inhibition of drug efflux in endothelial cells of brain capillaries, appears to be the most promising modality. The same refers to the methods of intracellular transport of drug suspensions developed recently. All these achievements provide a solid basis for the further improvement of drug pharmacokinetic properties, reduction of systemic toxicity, increase of therapeutic efficacy, and earlier diagnosis of CNS pathology.
Probable fatal cardiac dysrhythmia secondary to diuretic-induced hypokalemia (1981)

This case study describes the investigation of the sudden, unexpected death of a young, slightly hypertensive woman. She had a previous history pf serious hypokalemic-induced cardiac dysrhythmias associated with diuretic usage. Postmortem examination revealed no anatomic cause for her death. Her agonal plasma potassium, 5.4 mmol/L, seemed too low in light of her extreme acidosis, hypoxemia, and emergency treatment. Diuretic analysis indicated surreptitious ingestion of hydrochlorothiazide. Hypokalemia and the control of serum potassium concentration are discussed as are various modifiers of serum potassium.
Evolution of High Build-Rate RSS Changes the Approach to Unconventional Oil and Gas Drilling (2011)

Abstract This paper discusses the development, testing and optimization of a rotary steerable system (RSS) developed specifically to address the challenges around drilling wells in unconventional reservoirs in North America. As with offshore areas, rotary steerable drilling technology has rapidly gained acceptance for onshore use because of its clear advantages in directional control, wellbore placement and lateral reach, while matching or exceeding the drilling performance of conventional systems. The further growth of RSS into the drilling of unconventional reservoirs has been limited by the build-rate (BUR) capabilities of established RSS that prevent operators from successfully drilling curve and lateral sections in one run. In recent years, service companies have worked to improve the capabilities of rotary steerable drilling systems to meet the specific needs of drilling horizontal wells in unconventional oil and gas reservoirs. Due to lease spacing and limited vertical depths to achieve horizontal orientation, greater buildup rates (BUR) are required to maximize the lateral lengths in the reservoir. In addition to developing higher doglegs in the curve, the system should also enable lateral control to minimize tortuosity, facilitate easy casing running and optimize successful multistage fracturing. The authors outline how specific challenges, such as reduction in drilling time, improved wellbore placement, and more efficient completion and fracturing operations are addressed by the introduction of the new system. Included in this paper is a description of how the bottomhole assembly (BHA) and drill-bit properties are matched and optimized to deliver best directional control and drilling performance, according to formation characteristics in the Granite Wash play in the central USA. Explanations detail how the new system capabilities expand the possibilities to develop reservoirs using pad drilling, the use of more complex well profiles and real-time reservoir navigation, leading to increased hydrocarbon production.
Spectral clustering and transductive learning with multiple views (2007)

We consider spectral clustering and transductive inference for data with multiple views. A typical example is the web, which can be described by either the hyperlinks between web pages or the words occurring in web pages. When each view is represented as a graph, one may convexly combine the weight matrices or the discrete Laplacians for each graph, and then proceed with existing clustering or classification techniques. Such a solution might sound natural, but its underlying principle is not clear. Unlike this kind of methodology, we develop multiview spectral clustering via generalizing the normalized cut from a single view to multiple views. We further build multiview transductive inference on the basis of multiview spectral clustering. Our framework leads to a mixture of Markov chains defined on every graph. The experimental evaluation on real-world web classification demonstrates promising results that validate our method.
Dynamics of spray impingement wall film under cold start conditions (2019)

Fuel film that adhered on engine walls from spray impingement is considered a primary source of harmful combustion emissions. However, the physics of the wall film formation, propagation, and breakup is not fully understood yet because of its multiphase nature. Existing literature has revealed that the mass transportation within the fuel film takes a wave propagation form. This article aims to identify the dynamics of the wall film during spray impingement via high-speed laser diagnostics. In this work, a single-hole injector was used and the spray impinged onto a stage made of sapphire glass for diagnostics purposes. Iso-octane was used as the fuel and 10% ethanol was blended to dope rhodamine 6G as the fluorescent species for laser excitation. Simultaneous optical measurements, such as laser-induced fluorescence and Mie scattering, are performed to obtain the characteristics of the wall film quantitatively. Various aspects of the wall film, including the frequency of the wave, wave speed, and wave height, are inspected. The impact of fuel temperature and wall temperature under typical cold-start conditions are also studied to investigate the temperature dependence of the wall film dynamics. The research is also intended to provide quantitative experimental data for numerical models for impingement prediction and thus help the process of emission reduction and combustion optimization of internal combustion engines.
Multicenter Comparative Study of Conventional Mechanical Gas Ventilation to Tidal Liquid Ventilation in Oleic Acid Injured Sheep (2008)

We performed a multicenter study to test the hypothesis that tidal liquid ventilation (TLV) would improve cardiopulmonary, lung histomorphological, and inflammatory profiles compared with conventional mechanical gas ventilation (CMV). Sheep were studied using the same volume-controlled, pressure-limited ventilator systems, protocols, and treatment strategies in three independent laboratories. Following baseline measurements, oleic acid lung injury was induced and animals were randomized to 4 hours of CMV or TLV targeted to "best PaO2" and PaCO2 35 to 60 mm Hg. The following were significantly higher (p < 0.01) during TLV than CMV: PaO2, venous oxygen saturation, respiratory compliance, cardiac output, stroke volume, oxygen delivery, ventilatory efficiency index; alveolar area, lung % gas exchange space, and expansion index. The following were lower (p < 0.01) during TLV compared with CMV: inspiratory and expiratory pause pressures, mean airway pressure, minute ventilation, physiologic shunt, plasma lactate, lung interleukin-6, interleukin-8, myeloperoxidase, and composite total injury score. No significant laboratories by treatment group interactions were found. In summary, TLV resulted in improved cardiopulmonary physiology at lower ventilatory requirements with more favorable histological and inflammatory profiles than CMV. As such, TLV offers a feasible ventilatory alternative as a lung protective strategy in this model of acute lung injury.
ChemInform Abstract: Synthesis and Evaluation of Geldanamycin‐Estradiol Hybrids. (1999)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Electronic Beam Combination of Fiber Amplifier Arrays (2008)

The first reference beam free phase-locking of a high-power fiber amplifier array is reported. We also present a theoretical model predicting that it is possible to phase over 100 elements using this technique.
The Septin-Binding Protein Anillin Is Overexpressed in Diverse Human Tumors (2005)

Anillin is an actin-binding protein that can bind septins and is a component of the cytokinetic ring. We assessed the anillin expression in 7,579 human tissue samples and cell lines by DNA microarray analysis. Anillin is expressed ubiquitously but with variable levels of expression, being highest in the central nervous system. The median level of anillin mRNA expression was higher in tumors than normal tissues (median fold increase 2.58; 95% confidence intervals, 2.19-5.68, P < 0.0001) except in the central nervous system where anillin mRNA levels were lower in tumors. We developed a sensitive reverse transcription-PCR strategy to show that anillin mRNA is expressed in cell lines and in cDNA panels derived from fetal and adult tissues, thus validating the microarray data. We compared anillin with Ki67 mRNA expression and found a significant linear relationship between anillin and Ki67 mRNA expression (Spearmann r approximately 0.6, P < 0.0001). Anillin mRNA expression was analyzed during tumor progression in breast, ovarian, kidney, colorectal, hepatic, lung, endometrial, and pancreatic tumors and in all tissues there was progressive increase in anillin mRNA expression from normal to benign to malignant to metastatic disease. Finally, we used anti-anillin sera and found nuclear anillin immunoreactivity to be widespread in normal tissues, often not correlating with proliferative compartments. These data provide insight into the existence of nonproliferation-associated activities of anillin and roles in interphase nuclei. Thus, anillin is overexpressed in diverse common human tumors, but not simply as a consequence of being a proliferation marker. Anillin may have potential as a novel biomarker.
Title IX as a change strategy for women in science and engineering . . . and what comes next(1) (2008)

What does Title IX have to do with women in science? ‡ Title IX is a mechanism that—when wielded—successfully affects change for women. Americans rightly attribute the Education Amendments of 1972, commonly called Title IX, with the spectacular increase in opportunities for female athletes in schools and colleges, but the law as originally written never mentioned athletics. It stated, “No person in the United States shall, on the basis of sex, be... denied the benefits of... any education program or activity receiving Federal financial assistance.” In analogy with the creative legal strategy that extended Title IX to school sports and led (with time and effort) to women comprising 42 % of today’s collegiate athletes, I argued in 2000 that it was time to apply Title IX as a strategy on behalf of women faculty in chemistry departments.(1) While that suggestion was met with near-universal horror,(2) look at the facts. Twenty percent of the Ph.D.s in chemistry went to women in 1985, increasing to 33 % by 1999. Yet the fraction of women on the tenure-track faculty of the top 50 research departments in chemistry in 2000 was only 10%, rising to 12 % in 2002 and stagnating at that level in 2003 and 2004.(3) Chemistry is not the only discipline with solid Ph.D. numbers: women earn more than 40% of the Ph.D.s in the life sciences, more than 20 % of the Ph.D.s in chemical engineering, more than
Somatostatin receptor imaging in somatotroph and non‐functioning pituitary adenomas: correlation with hormonal and visual responses to octreotide (1997)

In the conditions of the study, in patients with acromegaly, positive somatostatin receptor scintigraphy predicts a hormonal response but the value of somatostatin receptor scintigraphy is limited by its low negative predictive value. In patients with non-functioning pituitary adenomas, negative somatostatin receptor scintigraphy predicts that there will be no visual improvement during octreotide treatment.
Abstract B263: Mechanistic, functional, and in vivo efficacy of inhibiting ETK/BMX in cancer models (2009)

Abstract Epithelial and endothelial tyrosine kinase (ETK), also known as bone marrow tyrosine kinase gene in chromosome X (BMX), belongs to the Burton's Tyrosine Kinase (BTK) family. ETK is a nonreceptor tyrosine kinases involved in tumorigenicity, adhesion, motility, angiogenesis, proliferation, and differentiation. It is overexpressed in metastatic breast and prostate cancers and is implicated in the neuroendocrine transformation of prostate cells. Significant oncogenes such as Src, focal adhesion kinase (FAK), and phosphatidyl-inositol (PI)-3 kinase are upstream regulators of ETK while several hub proteins, also critical for cancer development and progression, such as AKT, STAT3, and p21 activated kinase 1 (PAK1), are downstream of ETK. Cell-based validation studies also demonstrate that inhibition of ETK diminishes cellular transformation, proliferation, and migration. Such evidence provides substantial reasoning for developing new small molecule inhibitors against ETK. Applying SuperGen's proprietary small molecule drug discovery process, CLIMB™ a series of lead compounds were effectively developed to potently and selectively inhibit ETK. Biochemical data from kinase screens against ETK demonstrated nanomolar potency of SuperGen's inhibitors and good selectivity toward ETK from a panel of 75 kinases. To mechanistically demonstrate ETK inhibition in cell-based models, immunoprecipitations were carried out and phospho-ETK levels were detected. These compounds exhibited a dose-dependent response against phospho-ETK. Functionally, the inhibition of ETK will produce changes in phospho-AKT (S473) levels as well as phospho-STAT3 (Y705) levels downstream of EGF stimulation. Using Luminex bead-based technology and western blot techniques respectively, SuperGen's lead ETK compounds also yielded concentration-dependent responses with EC50 values in the nanomolar region. Given ETK's reported angiogenic role in endothelial cell migration and proliferation, these compounds were evaluated in an in vitro tube formation assay. Likewise, these ETK inhibitors demonstrated potent nanomolar inhibition of endothelial tube formation. Finally, having shown mechanistically and functionally the efficacy of ETK inhibitors through in vitro assays, the compounds were tested with in vivo solid tumor efficacy models in nude mice. All five lead inhibitors effectively decreased tumor burden volume relative to the vehicle treatment group in an AN3CA xenograft model. Taken together, these data suggest SuperGen's small molecule ETK inhibitors represent a potentially new therapeutic avenue for treating patients with solid tumor malignancies in the future. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B263.
Guidelines for Working Groups on Intellectual Property Issues (2004)

This memo lays out a conceptual framework and rules of thumb useful for working groups dealing with Intellectual Property Rights (IPR) issues. It documents specific examples of how IPR issues have been dealt with in the IETF.
Receptor for calcitonin gene-related peptide: binding to exocrine pancreas mediates biological actions (1985)

In the present study we demonstrate by immunohistochemical techniques that calcitonin gene-related peptide (CGRP) is present in nerve terminals in the islets of Langerhans. Furthermore, binding studies with 125I-CGRP indicate that dispersed acini from guinea pig pancreas contain a single class of high-affinity binding sites for CGRP with an apparent dissociation constant of 18 nM. Vasoactive intestinal peptide (VIP), rat growth hormone-releasing factor (rGRF), cholecystokinin octapeptide (CCK-OP), and bombesin do not interact with these receptors. Interaction of CGRP with these receptors leads to release of amylase from the acinar cells. Amylase release is half maximal at 0.3 nM CGRP and maximal at 3 nM CGRP. Maximal amylase release with CGRP is one-third of that observed with VIP. CGRP-induced amylase release is dependent on theophylline in the incubation medium. CGRP potentiates the amylase release stimulated by bombesin and CCK-OP but has no effect on amylase release stimulated by VIP, rGRF, and natural glucagon. CGRP stimulates a 25% increase in basal cellular cAMP. These results indicate that guinea pig pancreatic acinar cells contain a novel receptor for CGRP and that interaction of CGRP with this receptor leads to digestive enzyme secretion through a cAMP-mediated pathway. The presence of CGRP in the islets of Langerhans suggests a pathway for CGRP to reach the exocrine pancreas through an insuloacinar portal system.
Force-Sensor-Based Walking-Environment Recognition of Biped Robots (2020)

Usability of biped robots in real applications depends on the robot capability of stable and robust walking with high efficiency. To cope with the various practical challenges, the robot must therefore be able to recognize its environment properties. We report a system for indoor-surface detection based on force sensors attached below the feet of the robot. To verify the recognition performance, indoor evaluation surfaces with 5 different properties are used. The capability of fast surface-property recognition is realized by processing the stream of force-sensor data according to the method of overlapping sliding windows, in order to generate 4 different features in a dynamic way. A k-nearest-neighbor (kNN) classifier with multiple classes is applied for real-time high- accuracy recognition of the surface-specific robot-walking characteristics. In particular, recognition performance can be increased by combining the studied features into a single feature descriptor, instead of using each feature separately. Achievability of an overall accuracy of 90.4% and an average precision of 91.49% is verified. Thus, a favorable trade-off between cost and performance is realized. The developed method is useful for optimized dynamic robot-body balancing and walking-speed adjustment, according to the recognized surface properties.
"Limit on cross section 2" of "Search for supersymmetry in events with $b$-tagged jets and missing transverse momentum in $pp$ collisions at $\sqrt{s}=13$ TeV with the ATLAS detector" (2018)

Cross section excluded at 95% CL for b0L-SRA350 as a function of the sbottom and neutralino masses, for a pair produced sbottom with symmetric decay into a bottom and a neutralino.
Limiting Corrosion Problems Related to Dust-Control Agents (2014)

A wide variety of materials have typically been available to prevent the production of dust from unpaved surfaces. Dust-control agents mixed with fine soil can remain on metal surfaces on and under vehicles and aircraft and in some cases can greatly accelerate corrosion. Tests with potassium lactobionate (K-LB) solutions showed that the compound was an effective retardant and could reduce the rate of corrosion to ~25% of the corrosion rate of the water-soil control, reducing corrosion rates below that seen with lactobionic acid. Research indicates that effective dust control can be produced with far less corrosion if organic humectants are used.
The Roles of Lipoproteins, Diet, and Peripheral Macrophages in Atherosclerotic Disease (2015)

We consider lipid accumulation in atherosclerosis, with emphasis on mechanisms mediating atheroma growth at peripheral sites. Macrophages normally recycle all dead cell components, including membranes. Membrane lipids are exported, as cholesterol or cholesterol esters, by lipoproteins for disposal by the liver or, as triglycerides or phospholipids, for lipid storage or re-use. Membranes of somatic cells, such as red blood cells, incorporate fatty acids that reflect dietary intake. When excessive saturated and trans-unsaturated fats are incorporated in cells, and the cells die, macrophages cannot fully recycle the membrane lipids, setting up a vicious cycle of lipid overload, cell death, recruitment of macrophages, and cell proliferation. Semi-liquid masses of partially oxidized fatty acids and cholesterol, foamy macrophages, and proliferating stromal cells accumulate in arterial walls. The dramatic increase of atherosclerotic disease since 1920 reflects superabundant nutrition and altered dietary composition, along with reduced exercise and smoking. The dietary changes included increased saturated and trans-unsaturated fats. The biochemical basis of epidemic atherosclerosis includes a partial metabolic block in β-oxidation caused by unsaturated fatty acid intermediates. Responses of cells to un-degraded saturated and trans-fatty acids include production of inflammatory cytokines, alteration of macrophage signaling pathways, and altered lipid-handling enzymes. Prevention of disease is an ideal approach, but pharmacological inhibitors including statins, PCSK9 inhibitors, or limiting macrophage catabolism of lipids by reducing carnitine availability, may limit progression of atherosclerosis.
Photochemical Generation of Cyclopentadienyliron Dicarbonyl Anion by a Nicotinamide Adenine Dinucleotide Dimer Analogue (2001)

Irradiation of the absorption band of an NAD (nicotinamide adenine dinucleotide) dimer analogue, 1-benzyl-1,4-dihydronicotinamide dimer, (BNA)(2), in acetonitrile containing a cyclopentadienyliron dicarbonyl dimer, [CpFe(CO)(2)](2), results in generation of 2 equiv of the cyclopentadienyliron dicarbonyl anion, [CpFe(CO)(2)](-), accompanied by the oxidation of (BNA)(2) to yield 2 equiv of BNA(+). The studies on the quantum yields, the electrochemistry, and the transient absorption spectra have revealed that the photochemical generation of [CpFe(CO)(2)](-) by (BNA)(2) proceeds via photoinduced electron transfer from the triplet excited state of (BNA)(2) to [CpFe(CO)(2)](2).