gebhart/patrepeval huggingface dataset:
Abstract 12530: Tristetraprolin-mediated mRNA Degradation of Mitochondrial Electron Transport Chain Proteins Protects the Heart Against Iron Deficiency (2016)

Introduction: Iron deficiency is the most common nutrient deficiency in the world, and cells respond to iron deficiency by activating iron regulatory proteins (IRP) to increase cellular iron uptake and availability. Although iron overload can cause cardiomyopathy, iron deficiency does not normally lead to cardiac damage. Tristetraprolin (TTP) is a tandem zinc finger protein that binds to the AU-rich elements (AREs) in the 3’ untranslated regions (UTR) of mRNA molecules and causes their degradation. We recently showed that TTP plays a role in iron conservation in the cell by targeting and degrading the mRNA for the iron importer, transferrin receptor 1. However, it is not clear how cells respond to conditions when cellular iron uptake and availability are not sufficient to match the demand. We hypothesized that TTP protects against cardiac dysfunction under iron deficiency by targeting the mRNAs of Fe/S cluster-containing proteins in the mitochondria. Results: To assess the effects of TTP on mitochondria, we first performed an unbiased in silico screen and identified a number of mRNAs that contain the consensus TTP-binding sequence in their 3’ UTR. Of those, steady-state levels of several mRNAs were increased with TTP deletion. However, only the mRNAs of three genes were shown to be bound by and be degraded by TTP protein: NDUFS1 in complex I, UQCRFS1 in complex III and mitochondrial aconitase. Interestingly, these proteins need Fe/S clusters to be active, suggesting that their protein levels are decreased in the absence of Fe/S cluster availability. We also demonstrate that in the absence of TTP and with iron deficiency, complex III gets formed with UQCRFS1, but without the required Fe/S cluster, which leads to the production of reactive oxygen species (ROS) and cellular injury. Finally, mice with systemic deletion of TTP display cardiac dysfunction under iron deficiency, demonstrating a major role for TTP in maintaining normal cellular function under iron deficiency. Conclusions: Our results provide a pathway that is activated in parallel to the IRPs and leads to degradation of mitochondrial mRNAs that require Fe/S clusters. This response to iron deficiency is critical to prevent excessive ROS production and cardiac damage.
A Neural Network Approach to Quantify Blood Flow from Retinal OCT Intensity Time-Series Measurements (2020)

Many diseases of the eye are associated with alterations in the retinal vasculature that are possibly preceded by undetected changes in blood flow. In this work, a robust blood flow quantification framework is presented based on optical coherence tomography (OCT) angiography imaging and deep learning. The analysis used a forward signal model to simulate OCT blood flow data for training of a neural network (NN). The NN was combined with pre- and post-processing steps to create an analysis framework for measuring flow rates from individual blood vessels. The framework's accuracy was validated using both blood flow phantoms and human subject imaging, and across flow speed, vessel angle, hematocrit levels, and signal-to-noise ratio. The reported flow rate of the calibrated NN framework was measured to be largely independent of vessel angle, hematocrit levels, and measurement signal-to-noise ratio. In vivo retinal flow rate measurements were self-consistent across vascular branch points, and approximately followed a predicted power-law dependence on the vessel diameter. The presented OCT-based NN flow rate estimation framework addresses the need for a robust, deployable, and label-free quantitative retinal blood flow mapping technique.
Analytical Solutions for the Flexural Behavior of Metal Beams Strengthened with Prestressed Unbonded CFRP Plates (2018)

Trapezoidal prestressed unbonded retrofit (TPUR) systems have been recently developed and tested. The authors have already developed a comprehensive and accurate analytical solution for the TPUR system that takes many system parameters into account. The main aim of this paper is to develop a simplified analytical solution for predicting the behavior of metal beams that have been strengthened with the TPUR system. The developed analysis method can be useful to engineers because of its simplicity. An energy approach based on Castigliano's theorems is used to study the flexural behavior of a steel beam retrofitted with the TPUR system. A parametric study was performed and the comparative results showed that the results using Castigliano's first theorem are in agreement with the results using the flexibility approach.
Figure S2 from Dual Inhibition of IGF-1R and ErbB3 Enhances the Activity of Gemcitabine and Nab-Paclitaxel in Preclinical Models of Pancreatic Cancer (2023)

&lt;p&gt;Supplemental Figure S2: Istiratumab inhibits growth factor-induced AKT phosphorylation across a pancreatic cancer cell line panel.&lt;/p&gt;
Time domain rf characterisation of a thin-film metamorphic hemt under modulated backside illumination (2005)

It is shown in this paper how the opto-electrical interaction of a microwave device can be characterized by combining a large-signal network analyzer set-up with a modulated laser module. The concept is demonstrated by measuring a "thin film" M(etamorphic) HEMT under modulated optical (1550 nm laser light) illumination. The advantage of this approach is that the time-domain characteristics of the electrical currents, generated by the modulated laser light, can be visualised and analysed.
Peer-to-Peer Protocol (P2PP) (2007)

This document defines the Peer-to-Peer Protocol (P2PP), an
application-layer protocol, for creating and maintaining an overlay of
participant nodes. The overlay can be created using various structured
and unstructured peer-to-peer protocols such as Chord, Pastry,
Kademlia, Gnutella, and Gia.
Erste Ergebnisse der Immunlymphszintigraphie zur Diagnose des axillären Drüsenbefalles bei Mammakarzinom-Patientinnen (1986)

Sixteen patients suffering from breast cancer were investigated by the method of immunolymphoscintigraphy (ILS) to evaluate the axillary lymph node status. Two monoclonal tumour associated antibodies (HMFG-1 and HMFG-2) that are known to react strongly with a wide range of epithelial malignomas were used as tumour seeking agents in our recent study. All patients were operated a few days after the scanning procedure including a radical axillary lymph node dissection. Therefore the scan reports could be correlated in each case with the histology of the surgically removed probes. While HMFG-1 failed to show correct results, HMFG-2 gave accurate results in 9 of 13 cases of questionable lymph node involvement. Among the 4 false results, one turned out to be false positive and three false negative. If better antibodies or their fragments, respectively, are used, we are convinced this noninvasive approach will greatly improve preoperative diagnosis of lymphatic involvement in breast cancer patients.
Elevated O-GlcNAcylation promotes colonic inflammation and tumorigenesis by modulating NF-κB signaling (2015)

O-GlcNAcylation is a reversible post-translational modification. O-GlcNAc addition and removal is catalyzed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. More recent evidence indicates that regulation of O-GlcNAcylation is important for inflammatory diseases and tumorigenesis. In this study, we revealed that O-GlcNAcylation was increased in the colonic tissues of dextran sodium sulfate (DSS)-induced colitis and azoxymethane (AOM)/DSS-induced colitis-associated cancer (CAC) animal models. Moreover, the O-GlcNAcylation level was elevated in human CAC tissues compared with matched normal counterparts. To investigate the functional role of O-GlcNAcylation in colitis, we used OGA heterozygote mice, which have an increased level of O-GlcNAcylation. OGA(+/-) mice have higher susceptibility to DSS-induced colitis than OGA(+/+) mice. OGA(+/-) mice exhibited a higher incidence of colon tumors than OGA(+/+) mice. In molecular studies, elevated O-GlcNAc levels were shown to enhance the activation of NF-κB signaling through increasing the binding of RelA/p65 to its target promoters. We also found that Thr-322 and Thr352 in the p65-O-GlcNAcylation sites are critical for p65 promoter binding. These results suggest that the elevated O-GlcNAcylation level in colonic tissues contributes to the development of colitis and CAC by disrupting regulation of NF-κB-dependent transcriptional activity.
"PROTEOSILICA" A NOVEL NANOCOMPOSITE WITH PEPTIDE ASSEMBLIES IN SILICA NANOSPACE: PHOTOISOMERIZATION OF SPIROPYRAN DOPED IN CHIRAL ENVIRONMENT (2002)

Mesoporous silica composites filling densely peptide assemblies (Proteosilica) were newly synthesized as transparent films. Spiropyran guest was co-doped in the films and photo-isomerization between spiropyran form and merocyanine form was repeated by alternate irradiation of visible and UV lights. Circular dichroism (CD) active spectra were observed only for the spiropyran form in the Proteosilica with hexagonal geometry. However, the CD active behavior was absent for the spiropyran in lamellar Proteosilica. Difference in peptide assembling structures would affect chiral sensitivity of the doped spiropyran guest.
Activity-Monitoring Completion-Detection (AMCD): a new single rail approach to achieve self-timing (2002)

A new method for designing single rail asynchronous circuits is studied. It utilises additional circuitry to monitor the activity of nodes within combinational logic blocks. When all transitions have halted a completion signal is generated. Details of the circuit and design methodology are given and the influence of glitches on the proposed circuit is discussed. Three different levels of granularity are investigated. Experimental physical layout of the circuit with extracted and back-annotated simulation results is provided. The proposed approach results in faster operation than synchronous circuits with minimum circuit overhead incurred.
Post-ROSC electrocardiogram timing in the management of out-of-hospital cardiac arrest: results of an international multicentric study (PEACE study) (2020)

Abstract Background Electrocardiogram (ECG) is a key tool to triage out-of-hospital cardiac arrest (OHCA) patients after achieving a sustained return of spontaneous circulation (ROSC). According to current guidelines, an immediate coronary angiography is indicated only when the post-ROSC ECG discloses a ST-elevation myocardial Infarction (STEMI). Moreover, the 12-lead ECG should be recorded as soon as possible after ROSC, although it is reasonable that in the early post-ROSC stages ECG could reflect the ischemia secondary to cardiac arrest besides that of coronary origin possibly causing an overdiagnosis of STEMI (false positive). Purpose To assess whether the time from ROSC to ECG acquisition could affect the percentage of false positive ECG for STEMI. Methods We performed a retrospective, international, multicenter study (PEACE Study - NCT04096079). We included all patients over 18 years of age hospitalized after an OHCA due to medical cause at one of the three participating high-volume hospitals of three different European countries between 2015, 1st January and 2018, 31st December. We considered for the present study only patients who underwent coronary angiography and in whom a post-ROSC ECG was available. For the electrocardiographic diagnosis of STEMI the criteria established by the ESC 2017 guidelines were used, while the execution of a percutaneous coronary angioplasty (PTCA) was evaluated as an angiographic endpoint. We used logistic regression to evaluate the association of time to acquisition and the endpoint. We computed odds ratios and 95% confidence intervals (OR, 95% CI). Results Population consisted of 370 patients (77.6% male, mean age 61±13 years, median ROSC-ECG time 15 minutes). Post-ROSC ECG was positive for STEMI in 198 patients and in 39 of them (10.5%) a PTCA was not performed during urgent coronary angiography, representing the false positive (FP) ECG. Dividing the population in three tertiles according to the time from ROSC to ECG (≤7 mins; 8–33 mins; &amp;gt;33 mins), the percentage of FP-ECG in the first tertile (18.5%) was statistically significantly higher than in the second (7.2%, OR 2.9 (95% CI 1.1–7.5) p=0.025) and third (5.8%, OR 3.7 (95% CI 2.2–6.5) p&amp;lt;0.001) as also shown in the Figure. These differences remained significant when adjusting for sex, age, number of segments involved at ECG (anterior, lateral, posterior, inferior and right), QRS duration &amp;gt;120 msec, ECG heart rate &amp;gt;100 bpm and adrenaline administered &amp;gt;1 mg. Conclusion Our study offers the first demonstration that the acquisition of the 12-leads ECG too early after ROSC can misleadingly lead to the diagnosis of STEMI. Despite further validation are required, our data suggest that it may be reasonable to delay the acquisition of the ECG at least 8 minutes after ROSC or to repeat the acquisition if the first ECG, resulting diagnostic for STEMI, was performed very early. Figure 1 Funding Acknowledgement Type of funding source: None
Application of Combinatorial Methods for the Identifi cation of Synthetic Hair-Conditioning Polymers. (2022)

Cationic conditioning polymers have a role as deposition aids for depositing benefit agents such as silicone polymers and are used in shampoo formulations to provide improved combing properties, feel, and look. The objective of this work was to develop synthetic high-performance polymeric conditioning agents that exhibit conditioning performance as good as, or better than, the current commercially available polymers. We describe the application of high throughput methods to identify high-performance synthetic hair-conditioning polymers through using high throughput combinatorial methods for polymer synthesis and screening to prepare several hundred cationic polymer candidates. Shampoo formulations were then formulated with these polymers; hair tresses were treated with these formulations and tested <i>via</i> a parallel automated wet combing method. Three high-performing polymer candidates were selected for further evaluation, prepared on a larger scale and evaluated <i>via</i> a panel study. A (<i>3</i>-acrylamidopropyl)trimethylammonium chloride-vinyl monomer-based cationic copolymer is shown to exhibit hair conditioning efficiency equal to or greater than that of a high-performance cellulose ether-based polymer, SOFTCAT™ SL-5 (Polyquaternium-67) in a shampoo formulation.
A Gnutella inspired ubiquitous service discovery framework for pervasive computing environment (2008)

Pervasive computing, the new distributed computing paradigm aiming at providing services anywhere anytime, poses unique challenges on service management and discovery. In this paper, we propose a new pervasive computing framework named USDM-PerComp by using a Web Service Server/Directory Server (WSS/DS) based two-level hierarchical topology to address the challenges involved. DSs within USDM-PerComp autonomously form a peer-to-peer (P2P) overlay. We present a Gnutella inspired distributed algorithm to support service discovery over the resulted P2P overlay, and further implement a service crawler using mobile agent techniques to perform the discovery and invocation. With the service crawler, service composition could be done automatically and spontaneously without any user concern. Besides, we develop a distributed JPEG encoding application to verify the practicability of our proposal. Our experience confirms the scalability and flexibility of USDM-PerComp. The pervasive applications could be easily as well as efficiently created under USDM-PerComp environment.
Accelerating Frank-Wolfe with Weighted Average Gradients (2021)

Relying on a conditional gradient based iteration, the Frank-Wolfe (FW) algorithm has been a popular solver of constrained convex optimization problems in signal processing and machine learning, thanks to its low complexity. The present contribution broadens its scope by replacing the gradient per FW subproblem with a weighted average of gradients. This generalization speeds up the convergence of FW by alleviating its zigzag behavior. A geometric interpretation for the averaged gradients is provided, and convergence guarantees are established for three different weight combinations. Numerical comparison shows the effectiveness of the proposed methods.
Improved electron backscattering representation using a new class of distribution: application to EUV masks (2012)

Proximity Effects in electron beam lithography impact feature dimensions, pattern fidelity and uniformity. These effects are addressed using a mathematical model representing the radial exposure intensity distribution induced by a point electron source, commonly named Point Spread Function (PSF). PSF is generally approximated as a sum of Gaussian distributions. Recent works have emphasized that the Gaussian approximation was not perfectly suited in the case of Extreme UV mask substrates. In this case, an increase of backscattered energy is observed in the mid-range due to the high Z material used as an absorber in EUV mask substrates. A novel class of functions, namely Gamma probability distribution, is introduced as a new PSF model. In this work it is shown that the proposed model fits Monte-Carlo simulation data better than the conventional Gaussian model. Moreover, the analytic expression of the cumulative distribution function makes that the new model does not lead to an increase in computation complexity. Therefore, it is well suited for electron beam lithography simulation. We also show that it can be successfully implemented in Proximity Effect Correction algorithms.g
Understanding and Removal of False Contour in HEVC Compressed Images (2016)

A contour-like artifact called false contour is often observed in large smooth areas of decoded images and video. Without loss of generality, we focus on detection and removal of false contours resulting from the state-of-the-art High Efficiency Video Coding codec. First, we identify the cause of false contours by explaining the human perceptual experiences on them with specific experiments. Next, we propose a precise pixel-based false contour detection method based on the evolution of a false contour candidate (FCC) map. The number of points in the FCC map becomes fewer by imposing more constraints step by step. Special attention is paid to separating false contours from real contours such as edges and textures in the video source. Then, a decontour method is designed to remove false contours in the exact contour position while preserving edge/texture details. Extensive experimental results are provided to demonstrate the superior performance of the proposed false contour detection and removal method in both compressed images and videos.
A Direct-to-Biology High-Throughput Chemistry Approach to Reactive Fragment Screening (2021)

&lt;p&gt;Methods for rapid identification of chemical tools are essential for the validation of emerging targets and to provide medicinal chemistry starting points for the development of &lt;a&gt;new medicines. Here, we report a screening platform that combines ‘direct-to-biology’ high-throughput chemistry (D2B-HTC) with photoreactive covalent fragments. The platform enabled the rapid synthesis of &gt;1000 PhotoAffinity Bits (HTC-PhABits) in 384-well plates. Screening the HTC-PhABit library with &lt;/a&gt;carbonic anhydrase I (CAI) afforded 7 hits (0.7% hit rate), which were found to covalently crosslink in the Zn&lt;sup&gt;2+&lt;/sup&gt; binding pocket. A powerful advantage of the D2B-HTC screening platform is the ability to rapidly perform iterative design-make-test cycles, accelerating the development and optimisation of chemical tools and medicinal chemistry starting points with little investment of resource.&lt;/p&gt;
IMGN779, a CD33-Targeted Antibody-Drug Conjugate (ADC) with a Novel DNA-Alkylating Effector Molecule, Induces DNA Damage, Cell Cycle Arrest, and Apoptosis in AML Cells (2015)

Abstract IMGN779 is a CD33-targeting ADC consisting of a humanized anti-CD33 antibody, Z4681A, conjugated to DGN462, a novel DNA-alkylating agent, through a cleavable disulfide linker, sulfo-SPDB. CD33 is broadly expressed on leukemic blasts of patients with AML, making it a promising target for AML therapy. DGN462 is a member of the novel IGN class of DNA-acting cytotoxic agents, that consists of an indolino-benzodiazepine dimer containing a mono-imine moiety. Potent killing of AML tumor cells by DGN462 and IMGN779 has previously been demonstrated in vitro (K. Whiteman et. al, ASH 2014 #2321). Here we describe studies elucidating the mechanism of action of this novel payload in the AML cell lines: MV4-11, HL60, and EOL-1. The ability of DGN462 to alkylate DNA was demonstrated in an AML cell line by isolation and analysis of the genomic DNA from cells. DGN462 was found to co-purify with DNA, demonstrating that it covalently reacts with cellular DNA. A comet assay was performed confirming that DGN462 does not cross-link DNA. H2AX is known to be phosphorylated on serine 139 in response to DNA damage. Using flow cytometry, we assessed the phosphorylation of H2AX in AML cell lines following exposure to DGN462 and IMGN779. Increases in phosphorylated H2AX levels were detected as early as 4 hours following exposure to DGN462-SMe and 12 hours following exposure to IMGN779. Additional flow cytometry analysis showed that exposure to DGN462-SMe and IMGN779 leads to S-phase accumulation, G2/M arrest, followed by induction of apoptotic markers (cleaved PARP and cleaved Caspase-3) at later time points. Ex vivo studies using AML patient samples also showed elevation of phosphorylated H2AX and an increase in apoptosis in myeloid blasts following exposure to DGN462-SMe and IMGN779. As a demonstration of proof-of-mechanism in AML disease models, our results suggest that cell killing by IMGN779 is mediated by DNA damage, as a consequence of DNA alkylation. The DNA damage response is accompanied by cell cycle arrest, which leads to apoptosis. This relationship will be further explored in additional AML preclinical models to support the use of phosphorylated H2AX as a pharmacodynamic biomarker for IMGN779 activity in future clinical studies. Disclosures Krystal: ImmunoGen, Inc.: Employment, Equity Ownership. Walker:ImmunoGen, Inc.: Employment, Equity Ownership. Fishkin:ImmunoGen, Inc.: Employment, Equity Ownership. Audette:ImmunoGen, Inc.: Employment, Equity Ownership. Kovtun:ImmunoGen, Inc.: Employment, Equity Ownership. Romanelli:ImmunoGen, Inc.: Employment, Equity Ownership.