gebhart/patrepeval huggingface dataset:
Abstract 16412: Altered Nitroso/Redox Balance in Dystrophic Cardiomyopathy is Associated With NOS1 Uncoupling (2014)

Introduction: Dystrophic cardiomyopathy is the cardiac manifestation of Duchenne muscular dystrophy. Hearts from the mdx mouse, the mouse model of this disease, exhibit increased oxidative stress due to the up-regulation of NADPH oxidase.

Hypothesis: We tested the hypothesis that this oxidative stress disrupts the bioavailability of tetrahydrobiopterin (H4B) leading to defective nitric oxide (NO) production associated with NOS1 uncoupling.

Methods: We used mdx mice with established cardiomyopathy. Real-time PCR was used to evaluate NADPH oxidase -NOX2- and western blots were performed to assess protein expression or phospholamban (PLB) phosphorylation. NO production was assessed by either nitrate + nitrite measurement in heart homogenate or DAF-2 epifluorescence in myocytes. The degree of S-nitrosylation in myocytes was measured using immunofluorescence.

Results: We found a five-fold increased expression of NOX2 as well as increased superoxide production compared to wild type (WT; p<0.05 vs. WT) in mdx hearts. PLB phospho-Serine 16 was decreased (p<0.05 vs. WT) and PLB phospho-Threonine 17 was augmented (p<0.01 vs. WT) in mdx hearts and these changes were restored to normal by specifically inhibiting NOX2 with 20 microM VAS2870. In addition, NOS1 expression was increased eight-fold in mdx hearts compared to WT (p<0.05 vs. WT). Furthermore, cardiac NO production was reduced in mdx (p<0.05 vs. WT) and also was restored by VAS2870 in cardiomyocytes. There was less S-nitrosylation in mdx myocytes, which consistently showed decreased levels of S-nitroscysteines compared to WT. This paradoxical effect could be due to NOS1 uncoupling. To test this possibility, we treated isolated cardiomyocytes with 300 microM H4B and observed that NO production in mdx recovered to WT levels and S-nitrosylation levels were restored toward normal. H4B treatment also increased PLB phospho-Serine 16 but did not affect PLB phospho-Threonine 17.

Conclusions: These results suggest that NOX2-derived oxidative stress results in H4B oxidation, causing NOS1 uncoupling. Diminished NOS1 activity has functional implications for mdx cardiomyocyte performance.
Ion-Irradiation-Induced Cobalt/Cobalt Oxide Heterostructures: Printing 3D Interfaces (2020)

Interfaces separating ferromagnetic (FM) layers from non-ferromagnetic layers offer unique properties due to spin-orbit coupling and symmetry breaking, yielding effects such as exchange bias, perpendicular magnetic anisotropy, spin-pumping, spin-transfer torques, and conversion between charge and spin currents and vice versa. These interfacial phenomena play crucial roles in magnetic data storage and transfer applications, which require the formation of FM nanostructures embedded in non-ferromagnetic matrices. Here, we investigate the possibility of creating such nanostructures by ion irradiation. We study the effect of lateral confinement on the ion-irradiation-induced reduction of nonmagnetic metal oxides (e.g., antiferro- or paramagnetic) to form ferromagnetic metals. Our findings are later exploited to form three-dimensional magnetic interfaces between Co, CoO, and Pt by spatial-selective irradiation of CoO/Pt multilayers. We demonstrate that the mechanical displacement of O atoms plays a crucial role in the reduction from insulating, non-ferromagnetic cobalt oxides to metallic cobalt. Metallic cobalt yields both perpendicular magnetic anisotropy in the generated Co/Pt nanostructures and, at low temperatures, exchange bias at vertical interfaces between Co and CoO. If pushed to the limit of ion-irradiation technology, this approach could, in principle, enable the creation of densely packed, atomic-scale ferromagnetic point-contact spin-torque oscillator (STO) networks or conductive channels for current-confined-path-based current perpendicular-to-plane giant magnetoresistance read heads.
Parameter Estimation in Cellular Radio Systems (1999)

The problem to track time-varying parameters in cellular radio systems is studied. The focus is on estimation based only on the signals that are readily available. Previous work have demonstrated very good performance relying on analog measurement. In a real system most of the information is lost due to quantization and sampling at a rate that might be as low as 2 Hz (GSM case). Therefore a different approach is required and for that matter a Maximum Likelihood Estimator has been designed and exemplified in the case of GSM. The needed probability functions of the measurements cannot be described analytically. Instead point-mass approximations can be obtained from Monte-Carlo simulations for each point in a grid covering the interesting parameter space. The proposed algorithm can be tuned to track both slowly and fastly varying parameters individually. Since most computations take place in the base stations, the estimator is ready for implementation in a second generation wireless system. No update of the software in the mobile stations is needed.
Toward Application-Aware Security and Reliability (2007)

Clearly, the traditional one-size-fits-all approach to security and reliability is no longer sufficient or acceptable from the user perspective. A potentially much more cost-effective and precise approach is to customize the mechanisms for detecting security attacks and execution errors using knowledge about the expected or allowed program behavior.
Supplementary Methods and Legends from Inhibition of ALK, PI3K/MEK, and HSP90 in Murine Lung Adenocarcinoma Induced by <i>EML4-ALK</i> Fusion Oncogene (2023)

Supplementary Methods and Legends from Inhibition of ALK, PI3K/MEK, and HSP90 in Murine Lung Adenocarcinoma Induced by &lt;i&gt;EML4-ALK&lt;/i&gt; Fusion Oncogene
Using Mass Spectrometry to Detect, Differentiate, and Semiquantitate Closely Related Peptide Hormones in Complex Milieu: Measurement of IGF-II and Vesiculin (2014)

The search for an islet β-cell growth factor has been a key objective in recent diabetes research, because the ability to regenerate and/or protect the functioning β-cell population in patients could result in a great advancement for diabetes treatment. IGF-I and IGF-II are known to play crucial roles in fetal growth and prenatal development, and there is growing evidence that IGF-II increases β-cell proliferation and survival in vitro and in vivo. A search for the source of IGF-II-like immunoreactivity in isolated β-cell secretory granules from the murine cell line βTC6-F7 revealed a novel 2-chain IGF-II-derived peptide, which we named vesiculin and which has been shown to be a full insulin agonist. Here, we present a liquid chromatography-tandem mass spectrometry method that enables selective detection and semiquantitation of the highly related IGF-II and vesiculin molecules. We have used this method to measure these 2 peptides in conditioned media from 2 β-cell lines, produced under increasing glucose concentrations. This technique detected both IGF-II and vesiculin in media conditioned by MIN6 and βTC6-F7 cells at levels in the range of 0 to 6 μM (total insulin, 80-450 μM) and revealed a glucose-stimulated increase in insulin, IGF-II, and vesiculin. IGF-II was detected in adult human and neonatal mouse serum in high levels, but vesiculin was not present. The methodology we present herein has utility for detecting and differentiating active peptides that are highly related and of low abundance.
A Comment on the levels of antipsychotics and their metabolites in urine (2021)

A recent paper regarding development and validation of a liquid chromatography/mass spectrometry mass spectrometry (LC/MSMS) method for the analysis of antipsychotics and their respective metabolites in urine was published in the Journal of Analytical Toxicology. 7 This work by Kim, et al., was focused on assessing adherence of "mentally disordered probationers" to legally required antipsychotics. The authors note that the repercussions of "negative" test results could be severe and thus they have taken a very conservative approach to declaring negative results. This situation is the same as clinical patients who are prescribed antipsychotics and are monitored for their adherence to this paradigm by their physicians. Dosages for these drugs are set by medical practice as well as regulatory approvals. Again, the repercussions of negative test results can be serious. Any improvement in the effective sensitivity of the analytic method would benefit these patients.
Functionalized Mesoporous Silica Nanoparticles for Glucose‐ and pH‐Stimulated Release of Insulin (2014)

Abstract Multi‐stimuli responsive porous silica nanoparticles for controlled release of insulin were synthesized by tethering insulin molecules onto boronic acid‐functionalized mesoporous silica nanoparticles (BA‐MSNs) and then coating the BA‐MSNs with the bioadhesive and pH‐sensitive polymer polyacrylic acid (PAA). The insulin molecules were conjugated onto the exterior surfaces of BA‐MSNs via gluconic acid linker groups [or by making first the gluconic acid‐modified insulin (Gins)]. The surfaces of the resulting BA‐MSNs containing Gins were coated with PAA, which was used to protect the entrapped insulin from undergoing possible enzymatic degradations in such locations as the gastrointestinal (GI) tract. The PAA, which has excellent dispersibility and adherence to the mucosa, might also allow the permeation of such nanoparticles through the colon, and thereby improve their potential application for insulin delivery. The drug release properties of the resulting nanoparticles, denoted PAA‐Gins‐BA‐MSNs, as well as their control samples were studied in enzyme‐free simulated gastric fluid (SGF) (pH = 2.0), simulated intestinal fluid (SIF) (pH = 6.8), and phosphate buffer saline (PBS) (pH = 7.4). Because of their shrinkage at low pH and swelling at high pH, the PAA‐coated MSNs exhibited pH‐dependent insulin release properties. Besides pH, glucose was shown to trigger the release of insulin from the nanoparticles, which demonstrates the nanoparticles' multi‐stimuli‐responsive properties for controlled release of insulin. Finally, we show that the PAA‐coated MSNs were non‐cytotoxic.
Enhancement of KRS-XE for 50 keV Advanced Mask Making Applications (2002)

KRS-XE, a high performance chemically amplified photoresist designed specifically for e-beam mask making applications, has been enhanced to achieve reduced “footing” on chrome oxide surfaces while still maintaining the original lithographic characteristics that make KRS-XE a promising mask making candidate. These attributes include high resolution, superior bake latitudes, high vacuum stability, coated shelf life of greater than 2 months, and, most notably, the absence of a post exposure bake. In conjunction with the footing reduction the requisite sensitivity requirement of <10uC/cm2 with 50 keV exposure tools has been achieved while retaining the robust process latitude previously reported for this resist. Through a careful study of the photoresist formulation components a route to the ultra-high sensitivity of <2.5uC/cm2 at 50 keV has been elucidated which will further enhance throughput, decrease heating effects, and potentially be a suitable resist for e-beam projection lithography (EPL).
Supplementary Figure 7 from Therapeutic and Prophylactic Antitumor Activity of an Oral Inhibitor of Fucosylation in Spontaneous Mammary Cancers (2023)

&lt;p&gt;Splenocytes from mice provided normal water (open circle, n=8), 20mM 2FF (closed circle, n=8), or 50mM 2FF (triangle, n=7) for tumor prophylaxis showed a mean {plus minus} SEM IFN-ɣ response toward MMC lysate of 41.7 {plus minus} 6.35 (20mM group, p&lt;0.0001) and 47.8 {plus minus}11.1 CSPW (50mM group, p&lt;0.0001), compared to 5.63 {plus minus} 3.16 spots in untreated animals. The response was not dose dependent (p=0.603). No significant difference was observed for the two groups when stimulated with non-specific peptide HIV (20mM p=0.797; 50mM p=0.985) or Cyclin B1 (20mM p=0.984; 50mM p=0.978 ). ****p&lt;0.0001.&lt;/p&gt;
Subcriticality Measurement of Pressurized Water Reactors by the Modified Neutron Source Multiplication Method (2003)

Applicability of the modified Neutron Source Multiplication (NSM) method with extraction of the fundamental mode to subcriticality measurement has been investigated. This concept can be applied to the control rod worth measurement that is performed during reactor physics tests at periodical inspection of commercial PWRs. Following the feasibility verification in the previous study based on numerical analyses, its applicability has been proven in a more realistic situation; Regarding a withdrawal sequence of control rod banks during the PWR startup as a mockup experiment, subcriticalities with various control rod insertion patterns were estimated based on the modified NSM method. The subcriticality could be evaluated with good accuracy even with the mockup experiment where any special treatments for accurate measurement were not taken into account and furthermore the insensitivity of measuring signals by reactivity changes and their large fluctuations were seen. Some vital treatments for accurate estimatio...
Scaling point set registration in 3D across thread counts on multicore and hardware accelerator platforms through autotuning for large scale analysis of scientific point clouds (2017)

In this article, we present an autotuning approach applied to systematic performance engineering of the EM-ICP (Expectation-Maximization Iterative Closest Point) algorithm for the point set registration problem. We show how we were able to exceed the performance achieved by the reference code through multiple dependence transformations and automated procedure of generating and evaluating numerous implementation variants. Furthermore, we also managed to exploit code transformations that are not that common during manual optimization but yielded better performance in our tests for the EM-ICP algorithm. Finally, we maintained high levels of performance rate in a portable fashion across a wide range of HPC hardware platforms including multicore, many-core, and GPU-based accelerators. More importantly, the results indicate consistently high performance level and ability to move the task of data analysis through point-set registration to any modern compute platform without the concern of inferior asymptotic efficiency.
Effects of age and hypertension on autonomic nervous regulation during passive head-up tilt. (1994)

To study the effects of age and hypertension on autonomic nervous function with passive postural change, we examined 31 normotensive subjects (25 to 85 years old) and 31 hypertensive patients (21 to 71 years old) without any cardiac disease, diabetes mellitus, or neurological disorders. Subjects were passively placed in a 60 degrees head-up tilting position after 15 minutes in the supine position. Autonomic nervous function was evaluated by frequency domain analysis of heart rate with the autoregressive method. Using low-frequency (0.1 Hz) and high-frequency (0.25 Hz) peaks, the ratio of low- to high-frequency power (L/H) was calculated as an index of sympathetic activity and the ratio of high to total power (%HF) as that of parasympathetic activity. With the patient in the supine position, total power spectral density declined logarithmically with age in normotensive subjects and hypertensive patients, but %HF and L/H showed no changes. In response to passive tilting, L/H was increased and %HF was decreased in the normotensive subjects, and these responses declined with age logarithmically. In contrast, hypertensive patients exhibited less autonomic response to postural change regardless of age. These results suggest that autonomic neural response to tilt is decreased with age; however, attenuation of the response by hypertension is not associated with an increase in age.
Measurement of the distributions of event-by-event flow harmonics in lead-lead collisions at $ \sqrt{{{s_{NN }}}} $ = 2.76 TeV with the ATLAS detector at the LHC (2013)

A bstract The distributions of event-by-event harmonic flow coefficients v n for n = 2- 4 are measured in $ \sqrt{{{s_{NN }}}} $ = 2 . 76 TeV Pb + Pb collisions using the ATLAS detector at the LHC. The measurements are performed using charged particles with transverse momentum p T &gt; 0 . 5 GeV and in the pseudorapidity range | η | &lt; 2 . 5 in a dataset of approximately 7 μ b −1 recorded in 2010. The shapes of the v n distributions suggest that the associated flow vectors are described by a two-dimensional Gaussian function in central collisions for v 2 and over most of the measured centrality range for v 3 and v 4 . Significant deviations from this function are observed for v 2 in mid-central and peripheral collisions, and a small deviation is observed for v 3 in mid-central collisions. In order to be sensitive to these deviations, it is shown that the commonly used multi-particle cumulants, involving four particles or more, need to be measured with a precision better than a few percent. The v n distributions are also measured independently for charged particles with 0 . 5 &lt; p T &lt; 1 GeV and p T &gt; 1 GeV. When these distributions are rescaled to the same mean values, the adjusted shapes are found to be nearly the same for these two p T ranges. The v n distributions are compared with the eccentricity distributions from two models for the initial collision geometry: a Glauber model and a model that includes corrections to the initial geometry due to gluon saturation effects. Both models fail to describe the experimental data consistently over most of the measured centrality range.
Integrative Analysis Reveals Multiple Alterations of p53 Signaling Pathway Components In Primary Diffuse Large B-Cell Lymphomas (2010)

Abstract Abstract 635 Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease with infrequent alterations of multiple apoptotic, developmental and signaling pathways. Inactivating somatic mutations of the p53 tumor suppressor are uncommon in DLBCL, prompting speculation regarding alternative mechanisms of modulating p53 activity in this disease. As part of a comprehensive analysis of genetic alterations in DLBCL, we recently integrated high-resolution copy number data and transcription profiles in a series of 81 newly diagnosed previously untreated DLBCLs. Copy number (CN) alterations were evaluated using Affymetrix SNP Array 6.0 data on over 1.8 million genomic loci (906,000 SNP probe sets and 946,000 copy number probes) and a data-processing pipeline incorporating the normalization, calibration, and segmentation of the CN profiles and their analysis by the GISTIC algorithm. The genes within the peak and region of each GISTIC-identified alteration were tested for association with the corresponding transcripts' expression and significance values were corrected for multiple hypothesis testing by the false discovery rate (FDR) procedure, with the correction accounting for both the multiple genes within each peak and the multiple peaks. The signature for a given copy number alteration was then defined as the set of within-peak and -region transcripts with FDR q-values &lt; 0.25. The alteration signatures thus defined were then tested for pathway/gene set enrichment based on the hypergeometric distribution, using a compendium of gene sets from the MSigDB repository (Broad Institute). This analysis highlighted a genome-wide pattern whereby: i) individual pathways are targeted by multiple alterations at different loci (with different genes of the same pathway located within distinct CN alteration peaks or regions); and ii) members of multiple pathways are targeted by the same alteration (with genes co-located within a single CN alteration belonging to different pathways). The most highly significant enriched pathways (FDR &lt; .05) included apoptotic, p53 signaling, and ARF pathways and identified multiple modulators and effectors of normal p53 activity. These include: deletion of the MDM2-inhibitor, ARF; amplification of the p53 E3 ligases, MDM2 and COP1; deletion of p53 itself; deletion of the ribosomal protein that enhances p53 translation following DNA damage, RPL26; and deletion of p53 effectors including BNIP3L and DFFB. Of note, the deletion of 17p13.1 encompasses both p53 and its positive modulator, RPL26. In all cases, the observed alterations in p53 pathway components would decrease functionally active p53 protein and p53 apoptotic effectors in primary DLBCLs. Taken together, these data identify alternative genetic mechanisms for reducing p53 activity in DLBCL and highlight the value of an integrated comprehensive analysis of genetic alterations in this disease. Disclosures: No relevant conflicts of interest to declare.
Eph-ephrin signaling modulated by polymerization and condensation of receptors (2017)

Eph receptor signaling plays key roles in vertebrate tissue boundary formation, axonal pathfinding, and stem cell regeneration by steering cells to positions defined by its ligand ephrin. Some of the key events in Eph-ephrin signaling are understood: ephrin binding triggers the clustering of the Eph receptor, fostering transphosphorylation and signal transduction into the cell. However, a quantitative and mechanistic understanding of how the signal is processed by the recipient cell into precise and proportional responses is largely lacking. Studying Eph activation kinetics requires spatiotemporal data on the number and distribution of receptor oligomers, which is beyond the quantitative power offered by prevalent imaging methods. Here we describe an enhanced fluorescence fluctuation imaging analysis, which employs statistical resampling to measure the Eph receptor aggregation distribution within each pixel of an image. By performing this analysis over time courses extending tens of minutes, the information-rich 4D space (<i>x</i>, <i>y</i>, oligomerization, time) results were coupled to straightforward biophysical models of protein aggregation. This analysis reveals that Eph clustering can be explained by the combined contribution of polymerization of receptors into clusters, followed by their condensation into far larger aggregates. The modeling reveals that these two competing oligomerization mechanisms play distinct roles: polymerization mediates the activation of the receptor by assembling monomers into 6- to 8-mer oligomers; condensation of the preassembled oligomers into large clusters containing hundreds of monomers dampens the signaling. We propose that the polymerization-condensation dynamics creates mechanistic explanation for how cells properly respond to variable ligand concentrations and gradients.
Performance analysis of integrated voice/data multiplexing systems with local and remote data sources (2003)

Defines a discrete state continuous time Markov model for a range of integrated voice/data multiplexer (IVDM) systems. The system model is stated, and a method for exact analysis is given. Numerical results corresponding to a T1 rate are presented for three systems. Results are obtained for data sources that are local (high-speed access) or remote (DS0 voice channel rate access) to the multiplexer. It is shown that delays for remote data sources are higher than those for local sources, yet exhibit less variance. Furthermore, remote data sources allow optimal queuing power operation at efficiencies greater than that for local data sources.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Halogen bonding and other noncovalent interactions involving halogens: a terminology issue (2006)

Among the various intermolecular interactions involving halogens, halogen bonding refers to those in which halogens behave as acceptors of electron density.