gebhart/patrepeval huggingface dataset:
Abstract 2603: USP1 inhibitor synthetic lethality in BRCA1-mutant cancer is driven by PCNA ubiquitination (2022)

Abstract CRISPR-based functional genomic screening is a powerful approach for identifying novel classes of synthetic lethal drug targets. Here, we define the deubiquitinase USP1 as a synthetic lethal target in cancers with underlying DNA repair vulnerabilities. A highly potent and selective small molecule USP1 inhibitor conferred a viability defect in BRCA1-mutant, but not WT cell lines by activating replication stress. Genome-wide CRISPR screening uncovered RAD18 and UBE2K, which promote PCNA mono- and poly-ubiquitination respectively, as key mediators of USP1-BRCA1 dependency. Increased cellular mono- and poly-ubiquitination reduced PCNA protein levels, and restoration of PCNA protein expression rescued USP1 inhibitor sensitivity. USP1 dependency is associated with upregulated RAD18 and UBE2K expression, suggesting that elevated PCNA ubiquitination in the context of BRCA1 deficiency mediates USP1 synthetic lethality. Interestingly, USP1, but not PARP1 inhibition, elicited a viability defect in a subset of BRCA1/2 WT lung cancer cell lines, indicative of novel synthetic lethal interactions unique to USP1. Moreover, dual inhibition of PARP1 and USP1 are strongly synergistic in PARP1 inhibitor-responsive cell line models. Strong in vivo anti-tumor activity across multiple tumor models was demonstrated with USP1 inhibition alone and in combination with the PARP1 inhibitor olaparib. Our studies suggest that USP1 and PARP1 inhibitors target BRCA1-mutant cancer though distinct yet synergistic mechanisms. As such, USP1 inhibitors may provide novel treatment strategies for PARP1 inhibitor-resistant and -naïve BRCA1-mutant cancer. Citation Format: Justin Engel, Madhavi Bandi, Antione Simoneau, Katherine Lazarides, Deepali Gotur, Truc Pham, Shangtao Liu, Samuel Meier, Ashley Choi, Hongxiang Zhang, Binzhang Shen, Fang Li, Douglas Whittington, Shanzhong Gong, Xuewen Pan, Yi Yu, Lina Gu, Scott Throner, John Maxwell, Yingnan Chen, Alan Huang, Jannik Andersen, Tianshu Feng. USP1 inhibitor synthetic lethality in BRCA1-mutant cancer is driven by PCNA ubiquitination [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2603.
A Comprehensive Structural Overview of p38α MAPK in Complex with Type I Inhibitors (2015)

p38α mitogen-activated protein kinase (MAPK) is a well-recognized therapeutic target for the treatment of autoimmune and inflammatory diseases. Over the past two decades, tremendous efforts have been focused on the discovery and development of small-molecule p38α MAPK inhibitors, although currently no drugs targeting this protein are clinically available. Therefore, the identification of novel chemotypes that are able to inhibit p38α MAPK function is still of great therapeutic significance. With the objective to support drug discovery programs aimed at identifying new immunomodulators acting on p38α MAPK, herein we present a complete overview of the available crystal structures of this protein in complex with ATP-site type I inhibitors. The 85 available complexes are classified by chemotype and experimental binding mode, and the ligand-protein interactions are discussed using the most representative inhibitors. The type and frequency of key inhibitor features are analyzed to give a final summary of the chemical requirements of promising p38α MAPK inhibitors. The proposed pharmacophore can be exploited to enhance the opportunities to identify novel type I inhibitors of p38α MAPK.
Selecting Functional Test Sequences for Defect Diagnosis (2018)

A simulation-based design verification process creates a large pool of functional test sequences. Such sequences have several advantages when they are used as manufacturing tests and for defect diagnosis. This brief considers the problem of selecting functional test sequences from a given pool when the goal is to use the sequences for defect diagnosis. The procedure described in this brief relies on the defect diagnosis of faulty units for the selection of sequences. Experimental results for simulated faulty units based on benchmark circuits demonstrate the possibility of learning from a limited set of faulty units which sequences from a given pool are effective for defect diagnosis.
Search engine ranking efficiency evaluation tool (2007)

In view of the recent progress in the field of internet search engines, there is a growing need for mechanisms to evaluate the performance of these useful and popular tools. So far, the vast majority of researchers have relied on the information-retrieval metrics of "precision" and "recall" that quantify the occurrence of "hits" and "misses" in the returned list of documents. What they fail to do is to measure the quality of the ranking that the search engine has provided. This paper wants to rectify the situation. We discuss the issue in some detail, and then propose a new mechanism that we believe is better suited for our needs.
Improved accuracy and precision of calcium mass score using deconvolution and partial volume correction (2020)

There are multiple quantitative methods for assessing coronary calcifications with CT including Agatston, mass score, and volume score. Several studies have shown mass score in mg-calcium to be the most reproducible. Since we are interested in tracking changes in individual calcifications over time as a new biomarker of vascular disease, we have analyzed ways to further improve reproducibility. The conventional way to calculate calcium mass score is to sum all voxels above 130- HU and convert to mass score using a calibration constant. This does not account for blurring in CT system. To improve coronary calcification measurements, we used Richardson-Lucy deconvolution with a measured 2D and 3D impulse response (Philips IQon) and/or partial volume correction processing. At 120 kVp, we imaged a phantom with calcium inserts and calcified cadaver hearts at three rotational orientations at high (0.4883-mm, 0.67-mm-thick) and normal clinical (0.4883-mm, 2.5-mm-thick) resolution. For each calcification in clinical resolution images, in the order of partial volume correction, 2D deconvolution, and 3D deconvolution processing, averaged percentage difference to the actual value of the QRM phantom calcification inserts evaluation are 0.07,0.13 and 0.22, improves as for non-processed clinical evaluation is -0.41. Similarly, in cadaver hearts, accuracy for averaged percentage difference compared to high resolution results are -0.21, 0.29 and 0.09 respectively, improves as the clinical evaluation is -0.51. In all cases, precision across rotation angle improves as coefficient of variation are 0.09, 0.10 and 0.11 respectively in the same processing order, slightly improves compare to clinical evaluation 0.13.
Single-Sensor Camera Image Compression (2006)

This paper presents digital camera image compression solutions suitable for the use in single-sensor consumer electronic devices equipped with the Bayer color filter array (CFA). The proposed solutions code camera images available either in the CFA format or as the full-color demosaicked data, thus offering different design characteristics, performance and computational efficiency. Extensive experimentation reported in this paper indicates that pipelines which employ a JPEG 2000 coding scheme achieve significant performance improvements compared to similar processing pipelines equipped with a JPEG coder. Other improvements, both objective and subjective, are observed in terms of color appearance, image sharpness and the presence of visual artifacts in the captured images.
Pharmacological activities of some Argyranthemum species growing in the Canary Islands (2004)

Methanolic extracts of eight subspecies of genus Argyranthemum were evaluated against brine shrimps, human cancer cell lines, malarial parasites and microorganisms under in vitro conditions. In the shrimp assay, samples of A. adauctum ssp. adauctum, A. adauctum ssp. erythrocarpon and A. frutetescens ssp. succulentum were active with ED50 values in the range of around 300 to 360 microg/ml. In the Caco-2, HepG2 and MCF-7 cell lines, the samples A. adauctum ssp. jacobaeifolium and A. adauctum ssp. palmensis were active with LC50 values ranging between 80-90 microg/ml. The secondary assay results of antimalarial activity of samples, A. adauctum ssp. adauctum, A. adauctum ssp. dugourii, A. adauctum ssp. erythrocarpon and A. adauctum ssp. jacobaeifolium have IC50 values <50 microg/ml. The samples demonstrated broad specific antimicrobial activity against five different microorganisms.
APPLICATION OF HIGH-FLUIDITY AND NON-DRYING SHRINKAGE TYPE CONCRETE TO ART CONCRETE WALL AND LONG-TERM PREDICTION OF WALL STRAINS (2021)

Aiming to make defect-free reinforced concrete buildings, high-fluidity technology and non-drying shrinkage type concrete technology, using a new admixture, were combined to develop a suitable concrete for applications. This concrete was applied to a wall that embodied a refined design whereas it could not contain crack-inducing joints. 18 months after its construction, an investigation confirmed that no cracks were observed on the wall. Furthermore, based on research results on the effect of member thickness on drying shrinkage strain, a prediction of long-term strains in this wall was made showing the concrete expansive behavior that would be exhibited in the future.
Emerging Topical Onychomycosis Therapies –Quo Vadis? (2014)

Development of novel effective noninvasive topical therapy for treating onychomycosis and other nail diseases such as psoriasis is long overdue. Previously there was a lack of basic knowledge about nail and its barrier properties, but with the recent increased interest in this field both from industry and academia, we hope extensive research will continue in this field to bring about successful and safe treatments for such chronic diseases.
MÉLIDIS: Pattern recognition by intrinsic/discriminant dual modeling based on a hierarchical organization of fuzzy inference systems (2003)

Georges Stamon (Président et Rapporteur)&lt;br /&gt;Bernadette Bouchon-Meunier (Rapporteur)&lt;br /&gt;Maurice Milgram (Examinateur)&lt;br /&gt;Marc Parizeau (Examinateur)
A Method for Broadband Full-Duplex MIMO Radio (2012)

We present a time-domain transmit beamforming (TDTB) method for self-interference cancelation (SIC) at the radio frequency (RF) frontend of the receivers on broadband full-duplex MIMO radios. It is shown that the conventional frequency-domain transmit beamforming (FDTB) method along with the orthogonal frequency division multiplexing (OFDM) framework does not generally perform SIC in the prefix region of a transmitted frame. A hardware based test of the TDTB method shows a 50 dB SIC over a bandwidth of 30 MHz.
A sampling approach to finding Lyapunov functions for nonlinear discrete-time systems (2016)

This paper considers the problem of stability verification for discrete-time nonlinear systems via Lyapunov functions. Depending on the system dynamics, the candidate Lyapunov function and the set of initial states of interest, one generally needs to handle large, possibly non-convex or non-feasible optimization problems. To avoid such problems, we propose a constructive and systematically applicable sampling-based approach to stability analysis of nonlinear systems. This approach proposes verification of the decrease condition for a candidate Lyapunov function on a finite sampling of a bounded set of initial conditions and then it extends the validity of the Lyapunov function to an infinite set of initial conditions by exploiting continuity properties. This result involves no apriori analytic description of the continuity property and it is based on multi-resolution sampling, to perform efficient state-space exploration. Moreover, the stability verification is decentralized in the sampling points, which makes the method parallelizable. The proposed methodology is illustrated on two examples.
Transgene driving GFP expression from the promoter of the zona pellucida gene zpc is expressed in oocytes and provides an early marker for gonad differentiation in zebrafish (2003)

Although mechanisms of sex differentiation have been studied intensely in mammals, insects, and worms, little is known about this process in lower vertebrates. To establish a marker for female gonad differentiation in zebrafish, we generated a transgenic line in which 412 bp from the promoter and 5' mRNA leader of the female-specific zebrafish zona pellucida gene zpc are fused to the coding region of green fluorescent protein (GFP). The zpc0.5:GFP transgene is expressed exclusively in oocytes, starting from the onset of female-specific differentiation, and closely resembles the expression pattern of the wild-type zpc. Strong GFP expression persists throughout oogenesis and is visible through the body wall of females. We have also characterized a putative upstream factor of zpc, FIGalpha, and show that distribution of FIGalpha RNA is compatible with its postulated role in the regulation of zpc. The zpc0.5:GFP transgenic line described here will be useful for studying oocyte development and the mechanisms that determine sex-specific gene expression in the zebrafish. It is also the first promoter characterized to date to drive stable and efficient expression specifically in the zebrafish female germline.
Fiber Bragg grating sensors written by femtosecond laser pulses in micro-structured fiber for downhole pressure monitoring (2017)

In this paper, we demonstrate that femtosecond laser pulse written fiber Bragg gratings (FBGs) fabricated in specialty highly birefringent micro-structured optical fiber (MSF) can be used for high pressure and high temperature monitoring in downhole applications. The design of the micro-structure allows encoding the pressure information into the spectral separation between the two Bragg peaks reflected by the obtained MS-FBG. We obtained a differential pressure sensitivity of 3.30 pm/bar over a pressure range from atmospheric up to 1400 bar and at temperatures between 40 &deg;C and 290 &deg;C. Owing to the negligible differential pressure-temperature cross-sensitivity of 6.06E-3 bar/&deg;C, the proposed MSFBG sensor is an ideal candidate for pressure monitoring in the presence of high temperature transients.
Regulating exocytosis of nanoparticles via host–guest chemistry (2014)

Prolonged retention of internalized nanoparticulate systems inside cells improves their efficacy in imaging, drug delivery, and theranostic applications. Especially, regulating exocytosis of the nanoparticles is a key factor in the fabrication of effective nanocarriers for chemotherapeutic treatments but orthogonal control of exocytosis in the cellular environment is a major challenge. Herein, we present the first example of regulating exocytosis of gold nanoparticles (AuNPs), a model drug carrier, by using a simple host-guest supramolecular system. AuNPs featuring quaternary amine head groups were internalized into the cells through endocytosis. Subsequent in situ treatment of a complementary cucurbit[7]uril (CB[7]) to the amine head groups resulted in the AuNP-CB[7] complexation inside cells, rendering particle assembly. This complexation induced larger particle assemblies that remained sequestered in the endosomes, inhibiting exocytosis of the particles without any observed cytotoxicity.
An algorithm for petro-graphic colour image segmentation used for oil exploration (2011)

We propose a new heuristic algorithm for porosity segmentation for the coloured petro-graphic images. The proposed algorithm automatically detects the porosities that represent the presence of oil, gas or even water in the analyzed thin section rock segment based on the colour of the porosity area filled with dies in the analyzed sample. For the purpose of the oil exploration the thin section fragments are died in order to emphasize the porosities that are analyzed under the microscope. The percentage of the porosity is directly proportional to the probability of the oil, gas or even water presence in the area where the drilling is performed, i.e. the increased porosity indicates the higher probability of oil existence in the region. The proposed automatic algorithm shows better results to the existing K-means segmentation method.
The role of prolonged esophageal pH monitoring in the diagnosis of gastroesophageal reflux (1984)

To reassess 24-hour esophageal monitoring and determine if shorter time periods might retain its diagnostic benefits, we studied 16 gastroesophageal reflux (GER) patients and eight controls. Esophageal pH monitoring was performed for 24 hours, with patients in an upright position during the day and supine when retiring. During the 24-hour pH monitoring period, the mean percentage time that pH was less than 4.0 in GER patients, 13.2%± 2.9% (SEM), was significantly higher than in normal subjects, 0.7% ±0.2% (SEM). Analysis of individual data indicated clear separation of GER patients from normal subjects when in the upright posture, but 25% of GER patients were within the range of the normal subjects when supine (overnight). Three-hour time periods after meals were analyzed. Postprandial pH monitoring, when compared with 24-hour pH monitoring, can identify GER with a 77% sensitivity and a 96% specificity. A 12-hour period (four hours after the dinner meal and eight hours supine) can identify GER with a 94% sensitivity and a 100% specificity. We conclude that (1) 24-hour pH monitoring of the esophagus may have a continuing role in research aspects of GER, (2) 12-hour pH monitoring is a highly accurate test that could be adapted to patients' work schedules or to outpatient telemetry, and (3) post-prandial pH testing is a practical, less expensive, and accurate method of diagnosing GER that could be utilized by any gastroenterology diagnostic unit. (<i>JAMA</i>1984;252:1160-1164)
Relationship between serum indirect bilirubin levels and skeletal muscle mass in older male and female patients with type 2 diabetes (2022)

Serum indirect bilirubin levels may be associated with the decreased skeletal muscle mass in male older patients (aged 75 years and over) with type 2 diabetes.
Power Line Communication in a full electric vehicle: Measurements, modelling and analysis (2010)

The Power Line Communications technology is now considered as a good alternative for implementing communication grids also in vehicles, with the main scope consisting in reducing the cable harness. In this paper we present the first results relative to a study performed on a fully electric vehicle. Due to the peculiar characteristics of the power grid in electric vehicles (topology and noise), this study is important to verify whether the PLC technology is applicable also in this case.
Studies on Nucleolar RNA Synthesis in Drosophila Melanogaster: I. The Relationship between Number of Nucleolar Organizers and Rate of Synthesis (1972)

ABSTRACT Nucleolar RNA synthesis in salivary glands from XX, XY, and XO larvae having different numbers of nucleolus organizers was examined autoradiographically following incubation of (he tissues in [3H]uridine. In addition, the presence or absence of secondary constrictions was monitored in neuroblast preparations using acridine orange staining. It was observed that: (1) The rate of nucleolar [3H]uridine incorporation is independent of the number of nucleolus organizers in the cell; (2) nucleolar incorporation in XO tissues is elevated relative to that observed in XX or XY material; and (3) where the number of organizers is in excess of the wild type (2), secondary constrictions form at only 2 of the nucleolus organizer sites. From these and related observations we suggest that there are 2 forms of transcriptional control for nucleolar RNA synthesis. One acts as an on-off control, influencing the formation of secondary constrictions at the nucleolus organizers. The other form modulates rates of transcription at organizers where constrictions have been formed.
An Adaptive Genetic Algorithm for the Capacitated Vehicle Routing Problem with Time Windows and Two-Dimensional Loading Constraints (2017)

In this paper, we present a generalisation of the Capacitated Vehicle Routing problem where customer demand is composed of two-dimensional weighted items, with a time windows, called 2L-CVRPTW. The objective consists in designing a set of trips, starting and terminating at a central depot, minimizing the total transportation cost with a homogenous fleet of vehicles based on a depot node. Items in each vehicle trip must satisfy the two-dimensional orthogonal packing constraint. In literature, several exact and approximate approaches was proposed to find the best and the most feasible solution to the problem. In this paper, we use an adaptive genetic algorithm (GA) to solve the 2L-CVRPTW using an ordered crossover operator. The effectiveness of our approach was demonstrated through experiments on benchmark instances. The results showed that our proposed approach is competitive in terms of the quality of the solutions found.
The behavior of Lamb waves in stressed polymer foils (1996)

The influence of externally applied unidirectional stress on the lowest-order Lamb modes of a 12-μm poly(ethylene terephthalate) (PET) film has been investigated both theoretically and experimentally. The Lamb wave dispersion was determined in a fully contactless way by using optical generation and detection of ultrasound. The elastic parameters of the film material were obtained by fitting the angle dependence of the low-frequency limit of the velocity of the fundamental Lamb modes. Whereas the dispersion of the symmetric mode S0 is only slightly influenced by an external stress, the antisymmetric mode A0 shows a transition from dispersion behavior determined by the elastic constants at small stresses to a behavior dominated by the applied stress at large stresses.
A newly defined KE parameter and its application in the design of scramjet engines (1996)

Traditional parameters used to measure the performance of low speed propulsion engines do not provide the information required for optimizing scramjet engine designs. This is due mainly to the inherent performance coupling among scramjet engine components. This coupling requires the use of a single parameter to measure the performance of each individual component, as well as the overall engine, in order to identify and quantify losses within the engine. This paper discusses the development of a newly defined, generalized kinetic energy efficiency parameter for measuring individual component and overall engine performance. Additionally, a unique equation was developed to gauge overall engine performance in terms of its individual components. Three generic scramjet engine test cases were evaluated to determine the kinetic energy efficiency’s ability to identify and quantify losses within the engine. Finally, the Hypersonic Research Engine data was revisited to investigate component performance loss contributions to the overall engine.
Dry Submicron Classification by a Small Blow Down Cyclone. (1992)

At present, dry powders are mainly classified using a vortex centrifge or sieving equipment, in which the lowest 50% cut size is still greater than one micrometer. Inpactor-type classifiers are capable of operating in the submicron range, but have low throughput and high energy consumption.Our new free vortex cyclones are capable of excellent sharp classification of dry powders in submicron cut sizes, especially by the use of a 5% to 15% blow-down flow rate from the dust collector chamber. A specified cyclone has been experimentally studied under various operating conditions using several kinds of test powders.