gebhart/patrepeval huggingface dataset:
55. AAVHSC Vectors Encoding Zinc-Finger Nucleases Mediate Efficient Targeted Integration at the Human AAVS1 Locus in CD34+ Human Hematopoietic Stem Cells (2015)

Zinc-finger nucleases (ZFN) are powerful genome editing tools that may be used to prevent expression of specified genes, correct mutations, or insert transgenes at safe harbor loci. ZFNs create double-stranded breaks at specified locations in the genome which may subsequently be repaired via the non-homologous end joining pathway to interrupt expression of a gene. Targeted integration of genes at pre-determined sites in the genome can be achieved through homology-directed repair of ZFN-mediated targeted double-strand breaks using a co-delivered donor construct. We recently isolated and characterized a panel of novel AAVs (AAVHSC) derived from CD34+ human hematopoietic stem cells (HSC) from healthy donors. We have previously shown that vectors derived from AAVHSCs have the ability to efficiently transduce CD34+ cells. Here we tested the hypothesis that delivery of ZFNs and donor DNA by AAVHSC vectors to CD34+ human cells results in the creation of double stranded site-specific breaks and subsequent efficient targeted transgene integration. A promoterless GFP gene was targeted to Intron 1 of the PPP1R12C gene in the AAVS1 locus such that expression would be driven by the endogenous PPP1R12C promoter following site specific transgene integration. ZFNs specific for PPP1R12C Intron 1 and donor DNA were packaged in AAVHSCs and used to transduce either K562 cells or primary human cytokine-primed peripheral blood CD34+ cells (PBSC). Flow-cytometric analysis at different time points post-transduction revealed specific GFP expression in ZFN + Donor-transduced cells but not in cells transduced with ZFN alone. The multiplicities of infection, ratio of ZFN:donor, and timing of transduction were optimized in K562 cells. Simultaneous transduction of AAVHSC encoding both ZFN and donor DNA at multiplicities of infection of 50,000 and 150,000 respectively was found to be optimal and resulted in GFP expression in up to 50% of transduced cells. Optimized conditions were confirmed in primary CD34+ PBSC from different donors. Targeted integration into AAVS1 was consistently found to be more efficient in CD34+ PBSC as compared with K562 cells, with GFP expression ranging from 10 to 65% of cells. Integrated GFP was expressed long term, with approximately 20% GFP positive cells persisting at 35 days post-transduction in vitro in the absence of selection. Targeted integration into the AAVS1 locus was independently confirmed by amplification using transgene-specific and chromosome-specific primers. Sequencing of the amplified vector chromosome junctions confirmed site-specific integration into AAVS1. No unexpected modifications were found at the junction of the AAVS1 chromosomal sequence and donor homology arms. These results indicate that AAVHSCs function as efficient delivery tools for genome editing in therapeutically relevant cells such as primary PBSC.
Abstract 2788: Design, optimization, and biological evaluation of potent irreversible inhibitors of BTK kinase (2011)

Abstract Bruton's tyrosine kinase (BTK) is a cytoplasmic nonreceptor tyrosine kinase belonging to the Tec family of kinases. Critical for its function, BTK contains a pleckstrin homology (PH) domain and Src homology SH3 and SH2 domains. It signals downstream of the B-cell receptor (BCR) and is centrally involved in B-cell development. Activation of B-cells by various ligands is accompanied by the translocation of BTK to the cell membrane where it binds phosphatidylinositol-3,4,5-trisphosphate through its PH domain. Activation of BTK results in downstream signaling through the PI3K/AKT, PLCγ, NFκB, and other signaling pathways important for B-cell development and function. Recent reports have shown the aberrant expression and function of BTK in some cancers, including B-cell malignancies. We describe here the design, synthesis, molecular modeling, and biological evaluation of a series of small molecule, inhibitors of BTK kinase. Our initial lead compounds were identified via cross-docking experiments utilizing the crystal structure of BTK kinase and screening a previously in-house explored kinase inhibitor scaffold. We subsequently carried out structure-activity relationship studies and optimized the lead structures, which have IC50 activities in the range of 1 to 10μM against BTK. A critical step in the optimization of this chemical series against BTK was to explore the possibility of adding a Michael's acceptor group to react with Cys481 in the ATP-binding pocket of BTK. Optimization efforts yielded the currently best leads, HCI-1684 and HCI-1685, which inhibit BTK with IC50 values of 12 and 45 nM, respectively. Modeling data suggest these compounds irrepressibly bind in the ATP-binding pocket of BTK. HCI-1684, HCI-1685 and other lead compounds were further evaluated in cell-based assays and were demonstrated to inhibit BTK function downstream of BCR activation. This series of BTK inhibitors were shown to decrease phospho-PLCγ1/2 levels and other downstream phosphorylation events in malignant B-cell cell lines, such as Ramos B. Compound optimization and biological evaluation of this chemical series and evaluation in animal pharmacodynamic endpoint studies will be presented. Taken together, these results suggest BTK is a potential therapeutic target in cancer and that HCI-1684 is an exciting agent to potentially treat B-cell malignancies Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2788. doi:10.1158/1538-7445.AM2011-2788
Automatic System for Obstructive Sleep Apnea Events Detection Using Convolutional Neural Network (2018)

Obstructive Sleep Apnea (OSA) is characterized by repetitive episodes of airflow reduction (hypopnea) or cessation (apnea), which, as a prevalent sleep disorder, can cause people to stop breathing for 10 to 30 seconds at a time and lead to serious problems such as daytime fatigue, impaired memory, and depression. This work intends to explore automatic detection of OSA events with 1-second annotation based on blood oxygen saturation, oronasal airflow, and ribcage and abdomen movements. Deep Learning (DL) technology, specifically, Convolutional Neural Network (CNN), is employed as a feature detector to learn the characteristics of the highorder correlation among visible data and corresponding labels. A fully-connected layer in the last stage of the CNN is connected to the output layer and constructs the desired number of outputs for sleep apnea events classification. A leave-one-out cross-validation has been conducted on the PhysioNet Sleep Database provided by St. Vincents University Hospital and University College Dublin, and an average accuracy of $79 .61$% across normal, hypopnea, and apnea, classes is achieved.
Revealing the Structural Organization of Gamma-irradiated Starch Granules Using Polarization-resolved Second Harmonic Generation Microscopy (2023)

Starch is a semi-crystalline macromolecule with the presence of amorphous and crystalline components. The amorphous amylose and crystalline amylopectin regions in starch granules are susceptible to certain physical modifications, such as gamma irradiation. Polarization-resolved second harmonic generation (P-SHG) microscopy in conjunction with SHG-circular dichroism (CD) was used to assess the three-dimensional molecular order and inherent chirality of starch granules and their reaction to different dosages of gamma irradiation. For the first time, the relationship between starch achirality (χ21/χ16 and χ22/χ16) and chirality (χ14/χ16) determining susceptibility tensor ratios has been elucidated. The results showed that changes in the structure and orientation of long-chain amylopectin were supported by the decrease in the SHG anisotropy factor and the χ22/χ16 ratio. Furthermore, SHG-CD illustrated the molecular tilt angle by revealing the arrangement of amylopectin molecules pointing either upward or downward owing to molecular polarity.
ChemInform Abstract: PHOTOCHEMISTRY OF AZIDOPENTACARBONYLTUNGSTATE(0) (1979)

Abstract Bei Bestrahlung des angeregten Zustands der Titelverbindung, der die geringste Energie hat, werden drei Photoreaktionen beobachtet, die Reaktion des koordinierten Azids unter N 2 ‐Abgabe in Gegenwart von zusätzlichem CO zu koordiniertem Isocyanat über ein Produkt mit koordiniertem Nitren, die Reaktion mit dem Tetraphenylarsoniumkation unter schnellem thermischem Verlust von Carbonylgruppen zu einem Produkt, das weder CO noch 123 Azid oder Isocyanat enthält und Abgabe von CO und Reaktion des intermediären Tetracarbonylkomplexes mit anderen Neutralliganden.
Static analysis for probabilistic programs (2013)

We propose an approach for the static analysis of probabilistic programs that sense, manipulate, and control based on uncertain data. Examples include programs used in risk analysis, medical decision making and cyber-physical systems. Correctness properties of such programs take the form of queries that seek the probabilities of assertions over program variables. We present a static analysis approach that provides guaranteed interval bounds on the values (assertion probabilities) of such queries. First, we observe that for probabilistic programs, it is possible to conclude facts about the behavior of the entire program by choosing a finite, adequate set of its paths. We provide strategies for choosing such a set of paths and verifying its adequacy. The queries are evaluated over each path by a combination of symbolic execution and probabilistic volume-bound computations. Each path yields interval bounds that can be summed up with a "coverage" bound to yield an interval that encloses the probability of assertion for the program as a whole. We demonstrate promising results on a suite of benchmarks from many different sources including robotic manipulators and medical decision making programs.
The Electric Origin of Magnetic Forces Theory: General Framework (2020)

This paper presents the first general framework to explain the magnetic force as a result of electric force interactions between current charges moving at any constant speed and combination. The explanation depends on analyzing the spreading electric field in the space and the movement of charges inside current elements. Previous work used special relativity to describe the magnetic force as an electric one, but this description contradicts the fact that electrically neutral wires stay neutral with or without current flowing through them, as well as, it does not facilitate the derivation of the infinitesimal laws of magnetism. In this paper, the provided explanation is proved by deriving the infinitesimal magnetic force law and Biot-Savart law using the basis of electric forces. This work lies at the intersection between Electrical Engineering and Physics, and it is important to understand what is magnetism and its origin. Such understanding may help engineers and scientists in making new advancements in magnetic materials and applied magnetic technologies.
REPAIR AND STRENGTHENING OF STEEL STRUCTURES USING CFRP COMPOSITES: AN OVERVIEW (2023)

Since decades, carbon fiber-reinforced polymer (CFRP) composites have been used for strengthening of concrete structures, for which the required design theories and techniques have been well developed. However, strengthening of steel structures still requires further development of relevant theories and techniques. In this paper, the main differences in design requirements for CFRP strengthening of concrete and steel members are discussed. In addition, an overview on the research at Empa on non-prestressed/prestressed bonded/ubonded strengthening systems using CFRP plates and rods for steel girders, plates and connections is given, and, a few projects for real application of the developed systems in steel bridges are briefly explained.
Architectural exploration and optimization for counter based hardware address generation (1997)

A set of automated system level techniques is presented for architectural exploration and optimization of counter based address generation units in real time signal processing systems. The goal is to explore different architectural alternatives available when mapping array references in order to select the most promising ones in area cost. The techniques are demonstrated on realistic test-vehicles, showing that architectural decision at early stages of the design process, can have a very large impact on the resulting area figure.
A One-Pot Synthesis of Ring-fused 1,3,5-Triazine-2,4(3H)-diones: Reactions with Chlorocarbonyl Isocyanate (1985)

Ring-fused 2,4-dioxo-1,2,3,4-tetrahydro-1,3,5-triazines are prepared by cyclocondensation of α-amino-N-heteroarenes with chlorocarbonyl isocyanate in the presence of tertiary amines.
Forecasting of bse sensex using simple exponential smoothing (SES) method (2021)

AbstractForecasting is the prediction of variable based on known past values of that variable or other related variables. The art of forecasting is learned by experience rather than by academic study. Forecasts must results in present action to improve future. In this study, we discussed about Simple Exponential Smoothing (SES) method. By using this method, we forecast the BSE SENSEX closing point value and then compare the method with the help of RMSE measure.
Pre-clinical development of non-steroidal estrogen receptor GPR30 targeted Tc-99m labeled analogues for breast and endometrial cancer imaging (2008)

3156 Introduction and rationale  Currently, the estrogen-based radioimaging agents used in clinical applications are not specific for either ER alpha or ER beta and do not differentiate between classical estrogen receptors and novel classes of estrogen receptors such as GPR30. Classical ER antagonist such as tamoxifen is agonists for GPR30, inducing cell proliferation, which may lead to secondary cancers of reproductive organs. As GPR30 is overexpressed in breast, endometrial and ovarian cancers, it is critical to evaluate GPR30 expression in cancer. Recently, we had identified the first GPR30-selective agonist G1, a non-steroidal  tetrahydro-3H-cyclopenta[c]quinoline. Towards this end we have developed non-steroidal G1-modified Tc-99m-labeled GPR30-targeted agents for cancer imaging.  Methods  The parent GPR30-targeted ligand G1 was modified by adding a chelating moiety through various linkers and radiolabeled with Tc-99m using the tricarbonyl approach. Radioligand receptor binding studies were performed on ER alpha/beta- and GPR30-expressing human breast cancer MCF-7 cells and GPR30-expressing human endometrial carcinoma Hec50 cells. Blocking studies were performed with the GPR30-specific ligand G1 and 17 beta-estradiol (E2) to determine GPR30 specificity. In vivo biodistribution studies were performed on ovariectomized female athymic mice bearing human endometrial cancer Hec50 tumors and human breast cancer MCF-7/18 tumors. Blocking studies were performed by co-injecting either G1 or E2. NanoSPECT/CT imaging studies were performed on live tumor-bearing animals to evaluate the potential of Tc-99m agents as cancer imaging agents.  Results  All Tc-99m labeled derivatives were highly stable in plasma for up to 24 hours. The LogP values of the Tc-99m labeled agents ranged from 4.6 - 5.5. In cell binding studies, the Tc-99m labeled agents demonstrated GPR30 specificity. Metabolism and animal studies revealed high liver and intestine uptake as well as radiometabolites in the urine. The Tc-99m-G-ethyne-pyridin-2-yl hydrazine displayed liver uptake of 13-16% ID/g as compared to 21-28% ID/g for Tc-99m-G-ethane- pyridin-2-yl hydrazine. In terms of tumor uptake, the Tc-99m-G-ethyne-pyridin-2-yl hydrazine yielded tumor uptake of 1.05% ID/g at 3 hr PI as compared to 0.40 % ID/g for the Tc-99m-G-ethane-pyridin-2-yl hydrazine and 0.69% ID/g for the Tc-99m-G-ethyne-picolylamine. In imaging studies, the Hec50 tumor was visualized in a live animal for up to 6 hours after injecting the Tc-99m labeled agent.  Conclusion  We have synthesized and evaluated a series of first generation GPR30 targeted radioimaging agents. These GPR30-targeted agents exhibit promising biodistribution characteristics and tumor uptake, and are important lead compounds for ongoing efforts to optimize the GPR30 targeting and imaging characteristics for diagnostic applications.
Non-Continuous Translation of Coat Protein and Ribonucleic Acid Polymerase Cistrons in MS2 Bacteriophage Ribonucleic Acid (1974)

In an MS2 phage ribonucleic acid (RNA)-directed in vitro protein-synthesizing system, the coat protein cistron and the adjacent RNA polymerase cistron are translated non-continuously. The ribosomes which have completed the synthesis of coat protein dissociate from the MS2 RNA and do not read through the intercistronic gap. Translation of the adjacent RNA polymerase cistron requires ribosomes other than those translating the coat protein cistron.
Profile of Jean-Pierre Sauvage, Sir J. Fraser Stoddart, and Bernard L. Feringa, 2016 Nobel Laureates in Chemistry (2017)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Large scale experimental trial of 5G mobile communication systems — TDD massive MIMO with linear and non-linear precoding schemes (2016)

Recently, NTT DOCOMO and Huawei conducted a large-scale experimental trial of key technologies for the 5th generation (5G) mobile systems. Downlink multi-user (MU) transmission with massive MIMO in the time-division duplex (TDD) mode is one of the technologies evaluated in this trial. With linear and non-linear downlink precoding schemes, we investigated the practical performance of MU massive MIMO systems under different numbers of users, user distributions, and different radio frequency channel calibration settings with up to 24 users deployed. When linear precoding is used, the cell spectrum efficiency reaches 39 bit/s/Hz, and it reaches 43 bit/s/Hz when non-linear precoding is used. In term of the cell throughput, up to 1.35 Gbps cell throughput was observed with a linear precoder and 100 MHz bandwidth; and 343 Mbps cell throughput was observed with a non-linear precoder and 20 MHz bandwidth. Based on these investigations, we verified the feasibility and performance of a TDD massive MIMO system for 5G mobile systems, and studied the impact of key factors on the system performance.
Trimethylphosphate as a Methylating Agent for Cross Coupling: A Slow-Release Mechanism for the Methylation of Arylboronic Esters (2018)

A methyl group on an arene, despite its small size, can have a profound influence on biologically active molecules. Typical methods to form a methylarene involve strong nucleophiles or strong and often toxic electrophiles. We report a strategy for a new, highly efficient, copper and iodide co-catalyzed methylation of aryl- and heteroarylboronic esters with the mild, nontoxic reagent trimethylphosphate, which has not been used previously in coupling reactions. We show that it reacts in all cases tested in yields that are higher than those of analogous copper-catalyzed reactions of MeOTs or MeI. The combination of C-H borylation and this methylation with trimethylphosphate provides a new approach to the functionalization of inert C-H bonds and is illustrated by late-stage methylation of four medicinally active compounds. In addition, reaction on a 200 mmol scale demonstrates reliability of this method. Mechanistic studies show that the reaction occurs by a slow release of methyl iodide by reaction of PO(OMe)<sub>3</sub> with iodide catalyst, rather than the typical direct oxidative addition to a metal center. The low concentration of the reactive electrophile enables selective reaction with an arylcopper intermediate, rather than nucleophilic groups on the arylboronate, and binding of tert-butoxide to the boronate inhibits reaction of the electrophile with the tert-butoxide activator to form methyl ether.
Unbiased testing of several hundred tumor-specific single nucleotide variants of a tumor for protective immunogenicity and CD8+ response reveals surprises. (2018)

Abstract Somatic mutations in cancer cells can give rise to new MHC epitopes referred to as neoepitopes. Neoepitopes have been clearly demonstrated to elicit an antigen specific T cell response, which are capable of mediating targeted killing of cancer cells. Despite recent advancements, exactly what criteria make a good neoepitope for personalized therapy is currently unknown. Here, using a syngeneic tumor of C57BL/6 mice, named FABF, we present results of an exhaustive and exhausting study where we have tested hundreds of long peptides each containing a single nucleotide variant (SNV) (with the mutation in the center of the peptide) for their ability to elicit tumor rejection and independently, CD8+ T cell response. We observe that (i) about 2% of all SNVs lead to generation of peptides that can mediate tumor rejection to any significant degree; (ii) each peptide alone elicits a modest protection, and a combination elicits stronger protective immunity, (iii) all the neoepitopes that elicit tumor rejection have poor binding affinity for MHC I, and have positive values for Differential Agretopic Index (1). (iv) Even though the protective responses are CD8-mediated, there is no correlation between a neoepitope’s ability to elicit a CD8 response and tumor rejection. Some of these observations are inconsistent with some aspects of the current consensus about the defining characteristics of good neoepitopes.
Multispectral image retrieval using a distance based on vector quantization (2006)

This paper proposes a new method of similar image retrieval based on the spectral distribution of a multispectral image. The greatest advantage of multispectral imaging is that the color and reflectivity of the object can be determined accurately. In similar image retrieval these physical variables must be discriminated and accurately evaluated. However, in the conventional retrieval method, the color composition ratio is emphasized rather than evaluation of the color (as a physical variable). In the histogram intersection method, for example, which is a form of similarity calculation based on the histogram, the similarity is calculated from only the shape of the histogram, that is, the color composition ratio. Thus, the similarity may be understated simply because the composition ratio is different, which makes this approach unsuitable for multispectral image retrieval, in which the color similarity itself is to be evaluated. This paper proposes a method of retrieval which does not depend on the color composition ratio (a physical variable), but is based on the similarity of the physical variable itself. The method is based on the distance between images, which accurately represents the difference in the physical variables by vector quantization. The effectiveness of the proposed method is demonstrated by an experiment on similar image retrieval for multispectral images. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 89(11): 19–29, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.20273
Observation of Rayleigh-Taylor-like Structures in a Laser-Accelerated Foil (1984)

The development of the Rayleigh-Taylor hydrodynamic instability was studied in laser-accelerated targets by introduction of mass thickness variations in foil targets. Observations made by side-on flash x radiography showed target structures and mass redistribution effects which resemble Rayleigh-Taylor bubbles and spikes, including not only advanced broadening of the spike tips on the laser-irradiated side of the foil but also projections of mass on the unirradiated side. The observations compare well with numerical simulations.