gebhart/patrepeval huggingface dataset:
Data from Chemogenomic Landscape of <i>RUNX1</i>-mutated AML Reveals Importance of <i>RUNX1</i> Allele Dosage in Genetics and Glucocorticoid Sensitivity (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; &lt;i&gt;RUNX1&lt;/i&gt;-mutated (&lt;i&gt;RUNX1&lt;/i&gt;&lt;sup&gt;mut&lt;/sup&gt;) acute myeloid leukemia (AML) is associated with adverse outcome, highlighting the urgent need for a better genetic characterization of this AML subgroup and for the design of efficient therapeutic strategies for this disease. Toward this goal, we further dissected the mutational spectrum and gene expression profile of &lt;i&gt;RUNX1&lt;/i&gt;&lt;sup&gt;mut&lt;/sup&gt; AML and correlated these results to drug sensitivity to identify novel compounds targeting this AML subgroup.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; RNA-sequencing of 47 &lt;i&gt;RUNX1&lt;/i&gt;&lt;sup&gt;mut&lt;/sup&gt; primary AML specimens was performed and sequencing results were compared to those of &lt;i&gt;RUNX1&lt;/i&gt; wild-type samples. Chemical screens were also conducted using &lt;i&gt;RUNX1&lt;/i&gt;&lt;sup&gt;mut&lt;/sup&gt; specimens to identify compounds selectively affecting the viability of &lt;i&gt;RUNX1&lt;/i&gt;&lt;sup&gt;mut&lt;/sup&gt; AML.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; We show that samples with no remaining &lt;i&gt;RUNX1&lt;/i&gt; wild-type allele are clinically and genetically distinct and display a more homogeneous gene expression profile. Chemical screening revealed that most &lt;i&gt;RUNX1&lt;/i&gt;&lt;sup&gt;mut&lt;/sup&gt; specimens are sensitive to glucocorticoids (GCs) and we confirmed that GCs inhibit AML cell proliferation through their interaction with the glucocorticoid receptor (GR). We observed that specimens harboring &lt;i&gt;RUNX1&lt;/i&gt; mutations expected to result in low residual RUNX1 activity are most sensitive to GCs, and that coassociating mutations as well as GR levels contribute to GC sensitivity. Accordingly, acquired glucocorticoid sensitivity was achieved by negatively regulating &lt;i&gt;RUNX1&lt;/i&gt; expression in human AML cells.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our findings show the profound impact of &lt;i&gt;RUNX1&lt;/i&gt; allele dosage on gene expression profile and glucocorticoid sensitivity in AML, thereby opening opportunities for preclinical testing which may lead to drug repurposing and improved disease characterization. &lt;i&gt;Clin Cancer Res; 23(22); 6969–81. ©2017 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Kernel-based logistic regression model for protein sequence without vectorialization (2014)

Protein sequence data arise more and more often in vaccine and infectious disease research. These types of data are discrete, high-dimensional, and complex. We propose to study the impact of protein sequences on binary outcomes using a kernel-based logistic regression model, which models the effect of protein through a random effect whose variance-covariance matrix is mostly determined by a kernel function. We propose a novel, biologically motivated, profile hidden Markov model (HMM)-based mutual information (MI) kernel. Hypothesis testing can be carried out using the maximum of the score statistics and a parametric bootstrap procedure. To improve the power of testing, we propose intuitive modifications to the test statistic. We show through simulation studies that the profile HMM-based MI kernel can be substantially more powerful than competing kernels, and that the modified test statistics bring incremental gains in power. We use these proposed methods to investigate two problems from HIV-1 vaccine research: (1) identifying segments of HIV-1 envelope (Env) protein that confer resistance to neutralizing antibody and (2) identifying segments of Env that are associated with attenuation of protective vaccine effect by antibodies of isotype A in the RV144 vaccine trial.
The O 2 -independent pathway of ubiquinone biosynthesis is essential for denitrification in Pseudomonas aeruginosa (2020)

ABSTRACT Many proteobacteria, such as Escherichia coli , contain two main types of quinones, benzoquinones represented by ubiquinone (UQ) and naphthoquinones such as menaquinone (MK) and dimethyl-menaquinone (DMK). MK and DMK function predominantly in anaerobic respiratory chains, whereas UQ is the major electron carrier used for reduction of dioxygen. However, this division of labor is probably not so stric. Indeed, a pathway that produces UQ under anaerobic conditions in an UbiU-, UbiV- and UbiT-dependent manner has been recently discovered in E. coli while its physiological relevance is not yet understood because of the presence of MK and DMK in this bacterium. In the present study, we established that UQ 9 is the single quinone of P. aeruginosa and that is required for growth under anaerobic respiration (denitrification). We demonstrated that ORFs PA3911, PA3912 and PA3913 , which are homologues to the E. coli ubiT, ubiV and ubiU genes, respectively, were essential for UQ 9 biosynthesis and thus for denitrification in P. aeruginosa . These three genes were hereafter called ubiT Pa , ubiV Pa and ubiU Pa . We showed that UbiV Pa accommodates a [4Fe-4S] cluster. Moreover, we demonstrated that UbiU Pa and UbiT Pa were able to bind UQ and that the isoprenoid tail of UQ was the structural determinant for the recognition by these Ubi proteins. Since the denitrification metabolism of P. aeruginosa is believed to be important for pathogenicity in cystic fibrosis patients, our results highlight the O 2 -independent UQ biosynthesis pathway as a new possible target to develop innovative antibiotics.
Detecting the Interaction of Peptide Ligands with Plant Membrane Receptors (2017)

Abstract The field of plant receptor biology has rapidly expanded in recent years, however the demonstration of direct interaction between receptor‐ligand pairs remains a challenge. Click chemistry has revolutionized small molecule research but lacks popularity in plant research. Here we describe a method that tests for the direct physical interaction of a candidate receptor protein and a peptide ligand. This protocol describes the generation of the ligand probe, transient expression of a receptor protein, enrichment of membrane‐bound receptors, photo‐crosslinking and click chemistry‐mediated reporter addition, and detection of the receptor‐ligand complex. Copper‐based click chemistry confers several advantages, including the versatility to use almost any azide‐containing reporter molecule for detection or visualization of the complex and enables addition of the reporter molecule after receptor‐ligand binding which reduces the need for bulky ligand modifications that could interfere with the interaction. © 2017 by John Wiley &amp; Sons, Inc.
Capacity Improvement of Wireless Ad Hoc Networks with Directional Antennae (2006)

This paper investigates the scale law of network capacity of wireless ad hoc networks with phased array antennae and demonstrates its dramatic improvement over that with omni-directional antennae. The contributions of this paper are three-fold. First, we establish a general interference model for directional antennae of generic antenna patterns. Second, we argue that an arbitrary directional antenna pattern can be approximated by that of a phased array antenna. We investigate wireless networks with phased array antennae and derive the impact of nulls and null width in the antenna pattern on the scalability of network capacity. Third, we introduce a novel analytical approach that gives rise to a new set of network-capacity upper and lower bounds when directional antennae are used. We believe that this is the first work that shows that Theta(n) scalability in network capacity is achievable provided the dimension of the antenna array is sufficiently large
Kindlins, Integrin Activation and the Regulation of Talin Recruitment to αIIbβ3 (2012)

Talins and kindlins bind to the integrin β3 cytoplasmic tail and both are required for effective activation of integrin αIIbβ3 and resulting high-affinity ligand binding in platelets. However, binding of the talin head domain alone to β3 is sufficient to activate purified integrin αIIbβ3 in vitro. Since talin is localized to the cytoplasm of unstimulated platelets, its re-localization to the plasma membrane and to the integrin is required for activation. Here we explored the mechanism whereby kindlins function as integrin co-activators. To test whether kindlins regulate talin recruitment to plasma membranes and to αIIbβ3, full-length talin and kindlin recruitment to β3 was studied using a reconstructed CHO cell model system that recapitulates agonist-induced αIIbβ3 activation. Over-expression of kindlin-2, the endogenous kindlin isoform in CHO cells, promoted PAR1-mediated and talin-dependent ligand binding. In contrast, shRNA knockdown of kindlin-2 inhibited ligand binding. However, depletion of kindlin-2 by shRNA did not affect talin recruitment to the plasma membrane, as assessed by sub-cellular fractionation, and neither over-expression of kindlins nor depletion of kindlin-2 affected talin interaction with αIIbβ3 in living cells, as monitored by bimolecular fluorescence complementation. Furthermore, talin failed to promote kindlin-2 association with αIIbβ3 in CHO cells. In addition, purified talin and kindlin-3, the kindlin isoform expressed in platelets, failed to promote each other's binding to the β3 cytoplasmic tail in vitro. Thus, kindlins do not promote initial talin recruitment to αIIbβ3, suggesting that they co-activate integrin through a mechanism independent of recruitment.
High p16 expression and heterozygous RB1 loss are biomarkers for CDK4/6 inhibitor resistance in ER+ breast cancer (2022)

CDK4/6 inhibitors combined with endocrine therapy have demonstrated higher antitumor activity than endocrine therapy alone for the treatment of advanced estrogen receptor-positive breast cancer. Some of these tumors are de novo resistant to CDK4/6 inhibitors and others develop acquired resistance. Here, we show that p16 overexpression is associated with reduced antitumor activity of CDK4/6 inhibitors in patient-derived xenografts (n = 37) and estrogen receptor-positive breast cancer cell lines, as well as reduced response of early and advanced breast cancer patients to CDK4/6 inhibitors (n = 89). We also identified heterozygous RB1 loss as biomarker of acquired resistance and poor clinical outcome. Combination of the CDK4/6 inhibitor ribociclib with the PI3K inhibitor alpelisib showed antitumor activity in estrogen receptor-positive non-basal-like breast cancer patient-derived xenografts, independently of PIK3CA, ESR1 or RB1 mutation, also in drug de-escalation experiments or omitting endocrine therapy. Our results offer insights into predicting primary/acquired resistance to CDK4/6 inhibitors and post-progression therapeutic strategies.
Abstract 416: IL-33 Reduces Cardiac Remodeling, Inhibits Myocardial Apoptosis and Improves Survival After Experimental Myocardial Infarction (2007)

ST2 is an IL-1 receptor family protein with membrane-bound (ST2L) and soluble (sST2; extracellular portion of ST2L) isoforms. We have previously reported that serum sST2 predicts mortality in myoca...
NQR Line Broadening Due to Crystal Lattice Imperfections and Its Relationship to Shock Sensitivity (2004)

The hydrodynamic hot spot model is used to explain the difference between shock sensitive and shock insensitive explosives. Among the major factors that influence the shock sensitivity of energetic compounds are the quality and particle size of the energetic crystals used to formulate the cast plastic bonded explosive. As do all energetic compounds, RDX and HMX exhibit internal crystal defects the magnitude and type of which depend on the manufacturing process used to synthesize and re‐crystallize the energetic compound. Nuclear Quadrupole Resonance (NQR) spectroscopy was used to determine the crystal quality of RDX, HMX and CL‐20 obtained from various manufacturers. The NQR experimental results are discussed. Cast plastic bonded explosives were made using the RDX and HMX obtained from the various manufacturers and subsequently subjected to the NOL large‐scale gap test (LSGT). The results of the LSGT are discussed and correlated with the NQR results. A relationship between the crystal defect density and shock initiation pressure of the plastic bonded explosive is developed and discussed.
Experimental Characterization of Nonlinearity Mitigation by Digital Back Propagation and Nonlinear Polarization Crosstalk Canceller under High PMD condition (2011)

Impact of PMD is evaluated on nonlinear mitigation algorithm. While the backpropagation showed consistent improvement regardless of PMD, the best performance was found under different PMD conditions depending on fiber input power and channel spacing.
Sequential Testing for Sparse Recovery (2014)

This chapter contains sections titled: 1 Sequential Signal Sensing, 2 A Fundamental Problem—Sparse Support Recovery, 3 Motivation, 4 A Brief Historical Account of Sequential Analysis, 5 Sequential Probability Ratio Test, 6 SPRT In High Dimensions, 7 Sequential Thresholding for Sparse Support Recovery, 8 Conclusion, References
P31. CONTROL OF THE MINERALOCORTICOID RECEPTOR ENHANCES WOUND HEALING AND MITIGATE FIBROSIS AFTER THERMAL INJURY (2022)

PURPOSE: Adhesion, contracture, and the formation of disfiguring, hypertrophic scars remain some of the most recalcitrant problems in care of the burned patient. The central pathology driving fibrosis is an imbalance of extracellular matrix (ECM). The mineralocorticoid receptor (MR) is a nuclear receptor with shared ligand-activity from both its primary activator, aldosterone, and glucocorticoids and has cell specific effects on proliferation, migration, and ECM production in fibroblasts and keratinocytes. Here we demonstrate that MR-inhibition with FDA approved spironolactone enhances epithelialization healing and mitigates hypertrophic collagen deposition after burns in mice. METHODS: Female athymic mice sustained bilateral 1 cm full-thickness thermal injury and were stratified into either a) vehicle, b) spironolactone, c) aldosterone, or d) aldosterone + spironolactone. Aldosterone applied via subcutaneous pump (Alzet) spironolactone delivered intraperitoneally. Mice followed photographically for 4-to-6-weeks. At sacrifice wound biopsies were collected for H&E, Trichrome, and protein. RESULTS: Histologic evaluation of healing wounds from burned mice demonstrated persistence of inflammation, wound edema, and immature ECM. In mice treated with spironolactone this effect if alleviated by 4-weeks post-injury concurrent with gross findings of rapid wound epithelialization. Spironolactone treatment additionally enhanced gross and histologic evidence of scar resolution and resulted in a decreased in collagen staining vs. controls. CONCLUSION: We found a significant early improvement in wound epithelialization with spironolactone therapy. This suggests a potentially distinct effect from the proposed ECM-modifying strategy hypothesized. More analysis is needed but this data supports that MR-inhibition may be a valuable new therapeutic in treatment of burn scars.
Learning to fly (2019)

Hybrid unmanned aerial vehicles (UAV) combine advantages of multicopters and fixed-wing planes: vertical take-off, landing, and low energy use. However, hybrid UAVs are rarely used because controller design is challenging due to its complex, mixed dynamics. In this paper, we propose a method to automate this design process by training a mode-free, model-agnostic neural network controller for hybrid UAVs. We present a neural network controller design with a novel error convolution input trained by reinforcement learning. Our controller exhibits two key features: First, it does not distinguish among flying modes, and the same controller structure can be used for copters with various dynamics. Second, our controller works for real models without any additional parameter tuning process, closing the gap between virtual simulation and real fabrication. We demonstrate the efficacy of the proposed controller both in simulation and in our custom-built hybrid UAVs (Figure 1, 8). The experiments show that the controller is robust to exploit the complex dynamics when both rotors and wings are active in flight tests.
US tissue characterization workstation: applications and design. (1994)

This article discusses the purpose, design, and uses of an ultrasonographic tissue characterization workstation. The distinguishing characteristic of a tissue characterization workstation is its ability to analyze and classify image textures. Texture is defined as regularly or randomly repeating patterns. Small texture differences in an image are difficult to observe in the presence of noise. Therefore, it is necessary to analyze the image quantitatively. Quantitative measurements include run-length statistics, fractal dimension, and correlation statistics. The workstation is designed so that a radiologist can analyze the patient's images through an easy-to-use graphical user interface. The workstation software is based on standards, so that it can be run on a variety of different hardware platforms. The workstation can be used in a research environment to distinguish between images of malignant and benign breast lesions, which are difficult to diagnose visually. Further work is being done to make the workstation software into a useful clinical tool.
An evaluation of feature sets and sampling techniques for de-identification of medical records (2010)

De-identification of text medical records is of critical importance in any health informatics system in order to facilitate research and sharing of medical records. While statistical learning based techniques have shown promising results for de-identification purposes, few such systems are publicly available. It remains a challenge for practitioners to build an accurate and efficient system as it involves a significant amount of feature engineering, i.e. creation and examination of new features used in the system. A comprehensive evaluation is needed to thoroughly understand the effects of different feature sets and potential impacts of sampling and their trade-offs between the often conflicting goals of precision (or positive predictive value), recall (or sensitivity), and efficiency.
Surface Adsorption in Nonpolarizable Atomic Models (2014)

Many ionic solutions exhibit species-dependent properties, including surface tension and the salting-out of proteins. These effects may be loosely quantified in terms of the Hofmeister series, first identified in the context of protein solubility. Here, our interest is to develop atomistic models capable of capturing Hofmeister effects rigorously. Importantly, we aim to capture this dependence in computationally cheap "hard" ionic models, which do not exhibit dynamic polarization. To do this, we have performed an investigation detailing the effects of the water model on these properties. Though incredibly important, the role of water models in simulation of ionic solutions and biological systems is essentially unexplored. We quantify this via the ion-dependent surface attraction of the halide series (Cl, Br, I) and, in so doing, determine the relative importance of various hypothesized contributions to ionic surface free energies. Importantly, we demonstrate surface adsorption can result in hard ionic models combined with a thermodynamically accurate representation of the water molecule (TIP4Q). The effect observed in simulations of iodide is commensurate with previous calculations of the surface potential of mean force in rigid molecular dynamics and polarizable density-functional models. Our calculations are direct simulation evidence of the subtle but sensitive role of water thermodynamics in atomistic simulations.
Picosecond-petawatt laser-block ignition for avalanche fusion of boron by ultrahigh acceleration and ultrahigh magnetic fields (2016)

Fusion energy from reacting hydrogen (protons) with the boron isotope 11 (HB11) resulting in three stable helium nuclei, is without problem of nuclear radiation in contrast to DT fusion. But the HB11 reaction driven by nanosecond laser pulses with thermal compression and ignition by lasers is extremely difficult. This changed radically when irradiation with picosecond laser pulses produces a non-thermal plasma block ignition with ultrahigh acceleration. This uses the nonlinear (ponderomotive) force to surprizingly resulting in same thresholds as DT fusion even under pessimistic assumption of binary reactions. After evaluation of reactions trapped cylindrically by kilotesla magnetic fields and using the measured highly increased HB11 fusion gains for the proof of an avalanche of the three alphas in secondary reactions, possibilities for an absolutely clean energy source at comptitive costs were concluded.
H2O Vapor Transmission Rate through Polyethylene Naphthalate Polymer Using the Electrical Ca Test (2013)

The electrical Ca test was used to measure H2O vapor transmission through polyethylene naphthalate (PEN) polymer with a thickness of 200 μm. On the basis of the time required for the normalized conductance of the Ca film to reach zero, the H2O vapor transmission rate was determined versus H2O flux, temperature, and saturation of the PEN polymer with H2O. The H2O vapor transmission rate was proportional to the H2O flux and only weakly dependent on temperature at constant H2O flux. The transmission coefficient, Γ, for H2O through the PEN polymer at 70 °C was Γ ∼ 3.2 × 10(-10). The corresponding water vapor transmission rate (WVTR) at 70 °C/80% RH was 0.65 g/(m(2) day). The temperature dependence of the H2O vapor transmission rate through PEN at constant H2O flux yielded an activation barrier of E = 12.4 kJ/mol. There was no observable reservoir effect for H2O in the PEN polymer. The H2O vapor transmission rates for initially dry or H2O-saturated PEN polymer substrates were nearly identical at various temperatures. Although the time required for the normalized conductance of the Ca film to reach zero was inversely proportional to the H2O flux, the Ca film conductance did not decrease linearly versus H2O exposure. The Ca film conductance changed very little during initial H2O exposure. This behavior may be caused by the nonlinear oxidation kinetics of the Ca film.
Novel packaging of parallel-optical interconnects for high-end servers (2005)

A novel packaging concept is demonstrated where parallel-optical subassemblies are mounted on the same substrate as processor chips for processor-to-processor communication within a high-end server. A single-channel bit-error ratio <1.5/spl times/10/sup -15/ was measured at 8 Gbit/s.
Synthesis of azulitriphyrin(2.1.1) (2019)

A ring-contracted carbaporphyrin, azulitriphyrin(2.1.1), was synthesized via intramolecular McMurry coupling reaction. Absorption, NMR spectra and NICS calculations of protonated azulitriphyrin(2.1.1) revealed its Hückel aromatic character as a 14[Formula: see text] porphyrinoid.
Boron carbide fiber reinforced articles (2023)

Methods of producing continuous (or discontinuous) boron carbide fibers. The method comprises reacting a continuous or discontinuous carbon fiber material and a boron oxide gas within a temperature range of from approximately 1400.degree. C. to approximately 2200.degree. C. Articles including such partially or fully converted fibers may be provided, including such reinforcing fibers in a matrix of ceramic (a CMC), in metal (a MMC), or other matrix (e.g., polymer, etc.).