gebhart/patrepeval huggingface dataset:
In silico analysis of alternative splicing on drug-target gene interactions (2020)

Identifying and evaluating the right target are the most important factors in early drug discovery phase. Most studies focus on one protein ignoring the multiple splice-variant or protein-isoforms, which might contribute to unexpected therapeutic activity or adverse side effects. Here, we present computational analysis of cancer drug-target interactions affected by alternative splicing. By integrating information from publicly available databases, we curated 883 FDA approved or investigational stage small molecule cancer drugs that target 1,434 different genes, with an average of 5.22 protein isoforms per gene. Of these, 618 genes have ≥5 annotated protein-isoforms. By analyzing the interactions with binding pocket information, we found that 76% of drugs either miss a potential target isoform or target other isoforms with varied expression in multiple normal tissues. We present sequence and structure level alignments at isoform-level and make this information publicly available for all the curated drugs. Structure-level analysis showed ligand binding pocket architectures differences in size, shape and electrostatic parameters between isoforms. Our results emphasize how potentially important isoform-level interactions could be missed by solely focusing on the canonical isoform, and suggest that on- and off-target effects at isoform-level should be investigated to enhance the productivity of drug-discovery research.
Resonant Cavities for Dielectric Measurements (1947)

Fixed and variable length re-entrant resonant cavities designed for the measurement of dielectric constant and dissipation factor are described. These cavities operate in the frequency decade of 108 to 109 cycles per second, a region avoided by many experimenters because the frequency is too high for the application of circuit techniques and not high enough for the convenient use of coaxial lines or wave guides. The theoretical considerations in the design of these cavities are presented. The well-known susceptance variation method, widely used in the frequency range of 104 to 108 cycles per second, was extended to apply to these cavities; it yields a rapid measuring technique and very simple expressions for calculating the values of the dielectric properties. The performance of this apparatus is discussed and the results of the measurements of a few typical dielectrics are given.
Enhancing the Per-Unit-Length Data Density in Near-Field Chipless-RFID Systems With Sequential Bit Reading (2018)

In this letter, a novel near-field chipless-Radio Frequency Identification (RFID) system with sequential bit reading is reported. The main novelty concerns the tags, implemented by means of straight half-wavelength resonators separated by a small distance and forming a linear chain in the direction orthogonal to their axis. By this means, the number of resonant elements (or bits) per unit length of the tag is significantly increased, as compared to the previous implementations, with the result of very competitive tags in terms of data density. The active part of the reader is a microstrip line loaded with a shunt stub. Through a proper design, it is possible to achieve a significant excursion of the transmission coefficient when the stub is either loaded or unloaded with a functional resonant element of the tag. Consequently, by tag motion over the reader (stub), it is possible to infer the Identification (ID) code by simply injecting a harmonic signal to the input port of the stub-loaded line (the ID code is contained in the amplitude modulated, signal at the output port). This system has been validated by considering 100 b tags exhibiting a surface data density of 4.9 b/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . However, the relevant parameter is the data density per unit length, as high as 16.7 b/cm, i.e., much larger than previous values reported in the literature in similar chipless-RFID systems.
Application of artificial intelligence to forecast hydrocarbon production from shales (2017)

Artificial intelligence (AI) methods and applications have recently gained a great deal of attention in many areas, including fields of mathematics, neuroscience, economics, engineering, linguistics, gaming, and many others. This is due to the surge of innovative and sophisticated AI techniques applications to highly complex problems as well as the powerful new developments in high speed computing. Various applications of AI in everyday life include machine learning, pattern recognition, robotics, data processing and analysis, etc. The oil and gas industry is not behind either, in fact, AI techniques have recently been applied to estimate PVT properties, optimize production, predict recoverable hydrocarbons, optimize well placement using pattern recognition, optimize hydraulic fracture design, and to aid in reservoir characterization efforts. In this study, three different AI models are trained and used to forecast hydrocarbon production from hydraulically fractured wells. Two vastly used artificial intelligence methods, namely the Least Square Support Vector Machine (LSSVM) and the Artificial Neural Networks (ANN), are compared to a traditional curve fitting method known as Response Surface Model (RSM) using second order polynomial equations to determine production from shales. The objective of this work is to further explore the potential of AI in the oil and gas industry. Eight parameters are considered as input factors to build the model: reservoir permeability, initial dissolved gas-oil ratio, rock compressibility, gas relative permeability, slope of gas oil ratio, initial reservoir pressure, flowing bottom hole pressure, and hydraulic fracture spacing. The range of values used for these parameters resemble real field scenarios from prolific shale plays such as the Eagle Ford, Bakken, and the Niobrara in the United States. Production data consists of oil recovery factor and produced gas-oil ratio (GOR) generated from a generic hydraulically fractured reservoir model using a commercial simulator. The Box-Behnken experiment design was used to minimize the number of simulations for this study. Five time-based models (for production periods of 90 days, 1 year, 5 years, 10 years, and 15 years) and one rate-based model (when oil rate drops to 5 bbl/day/fracture) were considered. Particle Swarm Optimization (PSO) routine is used in all three surrogate models to obtain the associated model parameters. Models were trained using 80% of all data generated through simulation while 20% was used for testing of the models. All models were evaluated by measuring the goodness of fit through the coefficient of determination (R2) and the Normalized Root Mean Square Error (NRMSE). Results show that RSM and LSSVM have very accurate oil recovery forecasting capabilities while LSSVM shows the best performance for complex GOR behavior. Furthermore, all surrogate models are shown to serve as reliable proxy reservoir models useful for fast fluid recovery forecasts and sensitivity analyses.
Promoting Patient Safety within Implantable Medical Devices: Patient Alert™ (2005)

Implantable Cardioverter Defibrillator (ICD) systems have been shown to provide lifesaving therapy for patients at risk of sudden cardiac death due to ventricular tachyarrhythmia. In order to assure an ICD system is operating properly, some models of ICDs perform periodic system checks. The Patient Alert™ feature, in Medtronic® ICDs, monitors and alerts patients, via audible tones, to system integrity issues that have the potential to comprise patient safety. The objective of this research was to evaluate: how often patients are being alerted to ICD system issues, and how effective the alerts are at bringing patients into medical clinics for treatment and thus promoting patient safety. An analysis of 14,092 ICDs revealed that the probability of first alert occurrence increased with time since implant, but overall occurrence rates remained low (&lt; 7% per patient year). The average median time from the alert sounding until the patient received medical attention was 4.3 days. Overall, for a life-threatening condition such as ICD therapy delivery being turned off, the majority (76%) of patients with this alert were brought into a clinic within one week to have therapy delivery turned back on. To reach the remaining patients, as well as bring all patients in quicker to seek medial treatment, additional communication modalities are being planned for the next generation of ICD systems.
MHC and Non-MHC Genes in Lung Tumor Susceptibility in the Mouse: Implications for the Study of the Different Lung Tumor Types and Their Cell of Origin (1991)

Lung tumorigenesis in the mouse is controlled by multiple genes, which until now largely escaped detection because of the limitations of the available genetic tools. Therefore, we have developed the Recombinant Congenic Strains (RCS), which can be used to separate and map individual tumor susceptibility genes. The two strains, B10.O20/Dem and O20/A (used to produce the RCS series O20.c.B10.O20/Dem) differ in number, type, and degree of malignancy of lung tumors. Thus the genetic control of the different aspects of lung tumorigenesis can now be analyzed using RCS. The tests on the role of the Major Histocompatibility Complex (MHC; H-2 in mice) in lung tumorigenesis show that the H-2 influence is different for alveolar tumors and papillary tumors. In addition, only the development of papillary tumors is influenced by glucocorticoid administration concomitant with the transplacental carcinogen treatment. The MHC influence on lung tumor development is probably related to H-2 effects on the regulation of lung differentiation. In the H-2 congenic strains used papillary tumors developed early, whereas alveolar tumors appeared later, if at all. This differential impact of genetic and hormonal factors on the development of alveolar and papillary tumors suggests that they arise either from different cell types or from a common cell type at different stages of differentiation.
Upper bound of the diffraction efficiency of diffractive phase elements (1991)

An upper bound of the diffraction efficiency of diffractive elements that only influence the phase of the illumination wave is derived. The derivation only utilizes the specification of the desired diffraction pattern. It is independent of the technique to design and fabricate the diffractive element. The theory is based on the transmittance approach to describe the effect of the element on the illumination wave.
4‐Benzyloxy‐2,3,5‐morpholintrione und 3‐Benzyloxy‐2,4‐oxazolidindione aus N‐Benzyloxyglykolamiden und Oxalylchlorid (1986)

Abstract N‐Benzyloxy‐2‐hydroxycarbonamide 1 reagieren mit Oxalylchlorid in Abhängigkeit von der Substitution an C‐2 entweder zu 4‐Benzyloxy‐2,3,5‐morpholintrionen 5 und 3‐Benzyloxy‐2,4‐oxazolidindionen 3 oder ausschließlich zu dem Heterocyclus 5 . Die katalytische Hydrierung von 5 ergibt die N‐Hydroxyimide 8 .
Cyto-active amino-acid and peptide derivatives. Part I. Substituted phenylalanines (1954)

F. Bergel and J. A. Stock, J. Chem. Soc., 1954, 2409 DOI: 10.1039/JR9540002409
The requirements for a VHDL based custom IC, ASIC or FPGA design process (1993)

Examines a VHDL based design process and outlined some requirements for the tools and processes used in such a design process. Whilst doing this the author identifies a number of key areas where integration between tools and processes is important: a mixture of VHDL and standard graphical notations (DFD) and (FSM) is needed to specify the design in a way that can easily be communicated between different disciplines involved in the system design and partitioning; a common VHDL analyser/compiler for the simulation and synthesis tools will eliminate the risk of different interpretations of VHDL for simulation and synthesis; a mixed level simulation environment is desired where VHDL and high accuracy high performance gate level blocks can be simulated together; and scan insertion should he performed by the synthesis/optimisation tool and this should be closely integrated with the ATPG tool.
Myxoma Virus Lacking the Pyrin-Like Protein M013 Is Sensed in Human Myeloid Cells by both NLRP3 and Multiple Toll-Like Receptors, Which Independently Activate the Inflammasome and NF-κB Innate Response Pathways (2011)

The myxoma virus (MYXV)-encoded pyrin domain-containing protein M013 coregulates inflammatory responses mediated by both the inflammasome and the NF-κB pathways. Infection of human THP-1 monocytic cells with a MYXV construct deleted for the M013 gene (vMyxM013-KO), but not the parental MYXV, activates both the inflammasome and NF-κB pathways and induces a spectrum of proinflammatory cytokines and chemokines, like interleukin-1β (IL-1β), tumor necrosis factor (TNF), IL-6, and monocyte chemoattractant protein 1. Here, we report that vMyxM013-KO virus-mediated activation of inflammasomes and secretion of IL-1β are dependent on the adaptor protein ASC, caspase-1, and NLRP3 receptor. However, vMyxM013-KO virus-mediated activation of NF-κB signaling, which induces TNF secretion, was independent of ASC, caspase-1, and either the NLRP3 or AIM2 inflammasome receptors. We also report that early synthesis of pro-IL-1β in response to vMyxM013-KO infection is dependent upon the components of the inflammasome complex. Activation of the NLRP3 inflammasome and secretion of IL-1β was also dependent on the release of cathepsin B and production of reactive oxygen species (ROS). By using small interfering RNA screening, we further demonstrated that, among the RIG-I-like receptors (RLRs) and Toll-like receptors (TLRs), only TLR2, TLR6, TLR7, and TLR9 contribute to the NF-κB-dependent secretion of TNF and the inflammasome-dependent secretion of IL-1β in response to vMyxM013-KO virus infection. Additionally, we demonstrate that early triggering of the mitogen-activated protein kinase pathway by vMyxM013-KO virus infection of THP-1 cells plays a critical common upstream role in the coordinate induction of both NF-κB and inflammasome pathways. We conclude that an additional cellular sensor(s)/receptor(s) in addition to the known RLRs/TLRs plays a role in the M013 knockout virus-induced activation of NF-κB pathway signaling, but the activation of inflammasomes entirely depends on sensing by the NLRP3 receptor in response to vMyxM013-KO infection of human myeloid cells.
Alkaloids from the Sponge Monanchora unguifera (2005)

The bioassay-guided fractionation of the cytotoxic crude gum obtained from the Caribbean sponge Monanchora unguifera led to the isolation and characterization of the new compounds batzelladine J (1) and crambescidic acid (2) in addition to known guanidine alkaloids ptilomycalin A (3a), ptilocaulin (4), and isoptilocaulin (5). The structures of the compounds were elucidated by interpretation of the 1D and 2D NMR experiments. The chemotaxonomic implications of these findings are discussed.
Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 2. Treatment of some ROS- and Age-related diseases (heart arrhythmia, heart infarctions, kidney ischemia, and stroke) (2008)

Effects of 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) and 10-(6'-plastoquinonyl) decylrhodamine 19 (SkQR1) on rat models of H2O2- and ischemia-induced heart arrhythmia, heart infarction, kidney ischemia, and stroke have been studied ex vivo and in vivo. In all the models listed, SkQ1 and/or SkQR1 showed pronounced protective effect. Supplementation of food with extremely low SkQ1 amount (down to 0.02 nmol SkQ1/kg per day for 3 weeks) was found to abolish the steady heart arrhythmia caused by perfusion of isolated rat heart with H2O2 or by ischemia/reperfusion. Higher SkQ1 (125-250 nmol/kg per day for 2-3 weeks) was found to decrease the heart infarction region induced by an in vivo ischemia/reperfusion and lowered the blood levels of lactate dehydrogenase and creatine kinase increasing as a result of ischemia/reperfusion. In single-kidney rats, ischemia/reperfusion of the kidney was shown to kill the majority of the animals in 2-4 days, whereas one injection of SkQ1 or SkQR1 (1 micromol/kg a day before ischemia) saved lives of almost all treated rats. Effect of SkQR1 was accompanied by decrease in ROS (reactive oxygen species) level in kidney cells as well as by partial or complete normalization of blood creatinine and of some other kidney-controlled parameters. On the other hand, this amount of SkQ1 (a SkQ derivative of lower membrane-penetrating ability than SkQR1) saved the life but failed to normalize ROS and creatinine levels. Such an effect indicates that death under conditions of partial kidney dysfunction is mediated by an organ of vital importance other than kidney, the organ in question being an SkQ1 target. In a model of compression brain ischemia/reperfusion, a single intraperitoneal injection of SkQR1 to a rat (1 micromol/kg a day before operation) effectively decreased the damaged brain area. SkQ1 was ineffective, most probably due to lower permeability of the blood-brain barrier to this compound.
New Genes in Drosophila Quickly Become Essential (2010)

To investigate the origin and evolution of essential genes, we identified and phenotyped 195 young protein-coding genes, which originated 3 to 35 million years ago in Drosophila. Knocking down expression with RNA interference showed that 30% of newly arisen genes are essential for viability. The proportion of genes that are essential is similar in every evolutionary age group that we examined. Under constitutive silencing of these young essential genes, lethality was high in the pupal stage and also found in the larval stages. Lethality was attributed to diverse cellular and developmental defects, such as organ formation and patterning defects. These data suggest that new genes frequently and rapidly evolve essential functions and participate in development.
A Single-Layer Low-Profile Circularly Polarized Filtering Patch Antenna (2021)

A single-layer low-profile circularly polarized (CP) filtering patch antenna is investigated for wireless local area network (WLAN) applications. The CP antenna mainly consists of a feeding loop, four L-shaped radiating patches, and a square ground plane. To integrate the filtering function, four thin microstrip stubs and four shorting pins are introduced to the patches, and two U-shaped slots are etched in the feeding loop. These parasitic elements can realize the bandpass filtering function without requiring an external filter. In addition, these elements are skillfully added into the CP antenna, without increasing either the antenna footprint or profile. To verify the design, a prototype operating at 2.4 GHz WLAN band is fabricated and tested. The measured results show that the prototype has a low profile of 0.02λ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0</sub> , a passband bandwidth (|S <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">11</sub> | <; -10 dB and axial ratio (AR) <; 3 dB) of 4.1%, and a peak gain of 8.3 dBic. Moreover, the prototype also shows a sharp roll-off rate near the passband edge and a good out-of-band suppression level of more than 20 dB in the stopbands.
Gene expression during 3T3-L1 adipocyte differentiation. Characterization of initial responses to the inducing agents and changes during commitment to differentiation. (1992)

The mouse 3T3-L1 fibroblastic cell line rapidly differentiates to an adipocyte phenotype when post-confluent cells are treated for 48 h in fetal calf serum-containing medium supplemented with 1 microM dexamethasone (D), 0.5 mM methylisobutylxanthine (M) and 10 micrograms/ml insulin (I). D and I act synergistically to commit the cells to differentiate 24-48 h after initiating treatment, and this is blocked by the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate. In order to identify cellular proteins involved in the differentiation process we analyzed differentiating 3T3-L1 cells using two-dimensional electrophoresis on large format gels. We observed changes in over 300 proteins during differentiation (over 100 within 5 h of initiating differentiation) and many of these are also changed at the level of mRNA (by analysis of in vitro translation products). About 75% of the initial changes were maximally induced by treatment with a combination of M and I, while no more than 10 proteins and their corresponding mRNAs were maximally induced by D within 3.5 h. Another 10 proteins were synergistically regulated by the combination of all three agents (DMI) within 3.5 h. Additional species were induced at later times. Five of these were synergistically induced by treatments that lead to differentiation, were first expressed at elevated levels during commitment and remained elevated in fully differentiated adipocytes. One or more of these proteins could well have a functional role in the commitment to and/or expression of the adipocyte differentiation program.
Plasmid-based complementation of large deletions in Phaeodactylum tricornutum biosynthetic genes generated by Cas9 editing (2020)

The model diatom Phaeodactylum tricornutum is an attractive candidate for synthetic biology applications. Development of auxotrophic strains of P. tricornutum would provide alternative selective markers to commonly used antibiotic resistance genes. Here, using CRISPR/Cas9, we show successful editing of genes in the uracil, histidine, and tryptophan biosynthetic pathways. Nanopore long-read sequencing indicates that editing events are characterized by the occurrence of large deletions of up to ~ 2.7 kb centered on the editing site. The uracil and histidine-requiring phenotypes can be complemented by plasmid-based copies of the intact genes after curing of the Cas9-editing plasmid. Growth of uracil auxotrophs on media supplemented with 5-fluoroorotic acid and uracil results in loss of the complementing plasmid, providing a facile method for plasmid curing with potential applications in strain engineering and CRISPR editing. Metabolomic characterization of uracil auxotrophs revealed changes in cellular orotate concentrations consistent with partial or complete loss of orotate phosphoribosyltransferase activity. Our results expand the range of P. tricornutum auxotrophic strains and demonstrate that auxotrophic complementation markers provide a viable alternative to traditionally used antibiotic selection markers. Plasmid-based auxotrophic markers should expand the range of genome engineering applications and provide a means for biocontainment of engineered P. tricornutum strains.