gebhart/patrepeval huggingface dataset:
Competitive cAMP antagonists for cAMP-receptor proteins. (1984)

The two exocyclic oxygen atoms at phosphorus of cAMP have been replaced by a sulfur atom or by a dimethylamino group. These substitutions introduce chirality at the phosphorus atom; therefore, two diastereoisomers are known for each derivative: (SP)-cAMPS, (RP)-cAMPS, (SP)-cAMPN(CH3)2, and RP-cAMPN(CH3)2. We have investigated the agonistic and antagonistic activities of these compounds in four cAMP-dependent reactions: activation of the cellular slime mold Dictyostelium discoideum via its cell surface cAMP receptor, and phosphorylation by cAMP-dependent protein kinases type I, type II (both mammalian enzymes), and type D (derived from D. discoideum). The results show that 1) the compounds (SP)-cAMPS and (SP)-cAMPN(CH3)2 are (mostly full) agonists for the four proteins. Half-maximal activation is at micromolar concentrations (0.8-7 microM). 2) (RP)-cAMPS is a full antagonist for the cell surface receptor and protein kinases type I and II, with apparent inhibition constants between 0.8 and 8 microM. This compound is a partial agonist for protein kinase type D, where it induces maximally 50% activation of the enzyme if compared with cAMP. 3) (RP)-cAMPN(CH3)2 is a full antagonist for the cell surface receptor, and for protein kinase type II. This compound is a partial agonist for protein kinase type I (at least 50% activation if compared with cAMP), and inactive for protein kinase type D. This derivative is at least 25-fold less active as an antagonist than (RP)-cAMPS. 4) The activity of mixtures of different concentrations of the antagonist (RP)-cAMPS with different concentrations of cAMP reveals that the compound is a competitive antagonist of cAMP at micromolar concentrations.
Abstract 5213: A modified L-penetratin peptide targeting e2f-1, 2 and 3 is effective in combination with cisplatin or pemetrexed against prostate and lung cancer cell lines (2019)

Abstract Overexpression of the “activating” transcription factors, E2F1,2 and-3a induces genes involved in DNA synthesis and leads to cellular proliferation, tumor growth, and invasion. Therefore, inhibiting the overexpression of one or more activating E2Fs is a recognized target in cancer therapeutics. Dysregulation/overexpression of E2Fs is also controlled by deletion or mutations in the retinoblastoma protein in tumors. In our previous studies we showed that a novel penetratin conjugated 7-mer peptide (PEP) inhibited transcription of the E2F1, 2 and 3a by bounding tightly to E2F promoters. The PEP was cytotoxic at low micro molar concentrations to several malignant cell lines. As the PEP was unstable in vivo, the PEP was encapsulated in PEGylated liposomes (PL-PEP). Treatment of xenografts of the pRB negative small cell lung cancer H-69 and castrate resistant prostate cancer DU145 tumors propagated in mice with the PL- PEP, caused tumor regression. To increase stability and potency of the PEP, L-Arg in the PEP was replaced by D-Arg. Molecular simulation studies showed that the D-Arg PEP secondary structure is more stable than the L- Arg peptide structure in water. In vitro studies showed that the D-Arg PEP was more potent and more resistant to degradation by serum proteases than the L- form. As E2F is important for DNA repair, and for transcription of thymidylate synthase, we tested the effects of the PEP in combination with cisplatin, a DNA damaging drug and pemetrexed, a potent thymidylate synthase inhibitor. Combination studies of the D-ARG pep with cisplatin (in DU145, PC3, LnCap and 4T1) cells and with pemetrexed (in non-small cell lung cancer, H2009, H441, H1975 and H2228) resulted in synergistic cytotoxicity as determined by Chou-Talalay analysis. Citation Format: Gulam M. Rather, Michael Anyanwu, John E. Kerrigan, Kathleen W. Scotto, Olga Garbuzenko, Tamara Minko, Zoltan Szekely, Joseph R. Bertino. A modified L-penetratin peptide targeting e2f-1, 2 and 3 is effective in combination with cisplatin or pemetrexed against prostate and lung cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5213.
Broadband enhancement of spontaneous emission from nitrogen-vacancy centers in nanodiamonds by hyperbolic metamaterials (2013)

We experimentally demonstrate a broadband enhancement of emission from nitrogen-vacancy centers in nanodiamonds. The enhancement is achieved by using a multilayer metamaterial with hyperbolic dispersion. The metamaterial is fabricated as a stack of alternating gold and alumina layers. Our approach paves the way towards the construction of efficient single-photon sources as planar on-chip devices.
Two dimensional calculation of diffusive photocurrent in epitaxial bipolar devices (2003)

A 2D finite-difference model is presented that provides significant improvement over existing analytical approximations for the diffusive photocurrent generated in the collector by an epitaxial bipolar device when exposed to ionizing radiation. The model is used to gauge the effect of surface recombination on the amount of photocurrent generated. It is also used to compare the accuracy of several analytical approximations previously published in the literature.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
ChemInform Abstract: Synthesis of (+)‐Petasin and (+)‐Isopetasin, Constituents of Petasitis hybridus. (1995)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Novel tagging SNP rs1495741 and 2-SNPs (rs1041983 and rs1801280) yield a high prediction of the NAT2 genotype in HapMap samples (2012)

aUNC Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, North Carolina bAffymetrix Inc., Santa Clara, California, USA Correspondence to Dr Howard L. Mcleod, UNC Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, Campus Box 7361, Rm 1096 Genetic Medicine Building, 120 Mason Farm Rd, Chapel Hill, NC 27599-7360, USA Tel: +1 919 966 0512; fax: +1 919 966 5863; e-mail: [email protected] Received October 7, 2011 Accepted January 4, 2012
Integrative Molecular Characterization of Sarcomatoid and Rhabdoid Renal Cell Carcinoma Reveals Determinants of Poor Prognosis and Response to Immune Checkpoint Inhibitors (2020)

Abstract Sarcomatoid and rhabdoid (S/R) renal cell carcinoma (RCC) are highly aggressive tumors with limited molecular and clinical characterization. Emerging evidence suggests immune checkpoint inhibitors (ICI) are particularly effective for these tumors 1–3 , although the biological basis for this property is largely unknown. Here, we evaluate multiple clinical trial and real-world cohorts of S/R RCC to characterize their molecular features, clinical outcomes, and immunologic characteristics. We find that S/R RCC tumors harbor distinctive molecular features that may account for their aggressive behavior, including BAP1 mutations, CDKN2A deletions, and increased expression of MYC transcriptional programs. We show that these tumors are highly responsive to ICI and that they exhibit an immune-inflamed phenotype characterized by immune activation, increased cytotoxic immune infiltration, upregulation of antigen presentation machinery genes, and PD-L1 expression. Our findings shed light on the molecular drivers of aggressivity and responsiveness to immune checkpoint inhibitors of S/R RCC tumors.
Retroviral vectors (2020)

This chapter reviews the development of retroviral vectors, as well as some of the problems associated with their use and how these problems are currently being tackled. The DNA form of the retroviral genome must then integrate into the genome of the infected cell for the retroviral life cycle to proceed. The possibility that a similar mechanism may cause malignancies in patients treated with retroviral vectors carrying therapeutic genes intended to treat other preexisting medical conditions, has posed a recurring ethical problem. Silencing of expression or interference between promoters in retroviral vectors may be avoided by modifying or replacing the retroviral promoter. Retroviral vectors that are replication-competent may have to be used with this approach, particularly if the cells of a multicellular organ or dense tumour mass are to be targeted or if very high virus titres are required.
A finite dimensional $L_{\infty}$ algebra example in gauge theory (2005)

We construct an example of a finite dimensional L algebra which is generated by a Lie algebra together with a non-Lie action on another vector space. We then show how this example fits into the gauge transformation theory of Berends, Burgers and Van Dam.
Surge current capability of IGBTs (2012)

Commonly an IGBT cannot withstand a surge-current pulse (large overcurrent with a duration of some milliseconds) due to the current saturation characteristic of this device. In the case of a converter's single device failure the IGBT switches are driven into pulse-blocking mode to prevent a DC-link short-circuit and subsequent IGBT failures. This strategy leads to an asymmetric short circuit of the load. The paper introduces the possibility to symmetrize the load short circuit with active turned on IGBTs and shows first measurements on high-voltage press-pack IGBT chips under heavy overcurrent condition with increased gate voltage.
Invisible metallic mesh (2016)

A solid material possessing identical electromagnetic properties as air has yet to be found in nature. Such a medium of arbitrary shape would neither reflect nor refract light at any angle of incidence in free space. Here, we introduce nonscattering corrugated metallic wires to construct such a medium. This was accomplished by aligning the dark-state frequencies in multiple scattering channels of a single wire. Analytical solutions, full-wave simulations, and microwave measurement results on 3D printed samples show omnidirectional invisibility in any configuration. This invisible metallic mesh can improve mechanical stability, electrical conduction, and heat dissipation of a system, without disturbing the electromagnetic design. Our approach is simple, robust, and scalable to higher frequencies.
Effects of vacuum ultraviolet irradiation on trapped charges and leakage currents of low-k organosilicate dielectrics (2015)

Vacuum ultraviolet (VUV) photoemission spectroscopy is utilized to investigate the distribution of trapped charges within the bandgap of low dielectric constant (low-k) organosilicate (SiCOH) materials. It was found that trapped charges are continuously distributed within the bandgap of porous SiCOH and the center of the trapped states is 1.3 eV above the valence band of the tested sample. By comparing photoemission spectroscopic results before and after VUV exposure, VUV irradiation with photon energies between 7.6 and 8.9 eV was found to deplete trapped charge while UV exposure with photon energies less than 6.0 eV induces more trapped charges in tested samples. Current-Voltage (IV) characteristics results show that the reliability of dielectrics is improved after VUV irradiation with photon energies between 7.6 and 8.9 eV, while UV exposure results in an increased level of leakage current and a decreased breakdown voltage, both of which are harmful to the reliability of the dielectric. This work shows that VUV irradiation holds the potential to substitute for UV curing in microelectronic processing to improve the reliability of low-k dielectrics by mitigating the leakage currents and trapped charges induced by UV irradiation.
Uplink capacity studies for adaptive antenna arrays in third generation CDMA wireless systems (2003)

The effects of using adaptive antenna arrays in third generation CDMA wireless systems are analyzed through simulation studies. The capacity performance in multi-rate traffic scenarios of the reverse link is examined under various vector channel models and user population mixtures, along with comparisons with switched beam systems. The results indicate that adaptive antenna arrays have a clear advantage in mixed rate traffic in comparison to non-adaptive antenna techniques, while their performance is highly sensitive to channel conditions and the array topology.
Does Superior Bone Health Promote a Longer Lifespan? (2021)

Patients over 90 years of age had an overall low prevalence of fractures and relative preservation of bone health, suggesting a preserved bone molecular profile in these individuals. Epigenetic factors and activity levels might also have favorably affected bone health. The low percentage of osteoporosis and fractures likely reduced the morbidity and mortality in this population, potentially contributing to their overall longevity.
Optical Metrology Subsystem of the LISA Gravitational Wave Detector (2006)

We present a detailed concept for the realization of the LISA optical metrology subsystem, which employs heterodyne interferometry in a so-called “strap-down” architecture to accomplish a highly sensitive detection of gravity-wave induced displacements of dedicated mass references within the payload of the three LISA satellites. A frequency swap between transmitted and local reference beam is introduced to minimize the impact of stray light on the measurement sensitivity. The performance of the system is demonstrated by first optical modeling.
PromISR-6, a Guanabenz Analogue, Improves Cellular Survival in an Experimental Model of Huntington’s Disease (2019)

Guanabenz (GBZ), an α<sub>2</sub>-adrenergic agonist, demonstrated off-target effects that restored protein homeostasis and ameliorated pathobiology in experimental models of neurodegenerative disease. However, GBZ did not directly activate the integrated stress response (ISR), and its proposed mode of action remains controversial. Utilizing an iterative <i>in silico</i> screen of over 10,000 GBZ analogues, we analyzed 432 representative compounds for cytotoxicity in Wild-type, PPP1R15A-/-, and PPP1R15B-/- mouse embryonic fibroblasts. Nine compounds clustering into three functional groups were studied in detail using cell biological and biochemical assays. Our studies demonstrated that PromISR-6 is a potent GBZ analogue that selectively activated ISR, eliciting sustained eIF2α phosphorylation. ISRIB, an ISR inhibitor, counteracted PromISR-6-mediated translational inhibition and reduction in intracellular mutant Huntingtin aggregates. Reduced protein synthesis combined with PromISR-6-stimulated autophagic clearance made PromISR-6 the most efficacious GBZ analogue to reduce Huntingtin aggregates and promote survival in a cellular model of Huntington's disease.
REAKTIONEN VON THIOXOHETEROCYCLEN MIT N-CHLORAMIDEN 111.12- ODER 4-THIOPYRIDONE OHNE SUBSTITUENTEN AM STICKSTOFF UND NATRIUM-N-CHLORBENZOLSULFONAMIDE (1990)

Abstract 2- and 4-pyridinethiones (A) react with sodium N-chlorobenzenesulfonamides (1) in alcoholic solvents to N- (pyridy1thio)benzenesulfonamides (C), sodium N, N′-bis(phenylsulfonyl)-S-pyridylsulfodiimidates (D) and S-alkoxy-N-phenylsulfonyl-S-pyridylsulfimides (E). Constitution proofs for the new compounds D, E are reactions and 1H-, 13C-, 15N-nmr data. 2- und 4-Thiopyridone (A) reagieren mit Natrium-N-chlorbenzolsulfonamiden (1) in alkoholhaltigen Lösungsmitteln zu N- (Pyridylthio)benzolsulfonamiden (C), Natrium-N, N′-bis(phenylsulfony1)-S-pyridylsulfodiimidaten (D) und S-Alkoxy-N-phenylsulfonyl-S-pyridylsulfimiden (E). Konstitutionsbeweise für die neuen Verbindungen D, E sind Reaktionen sowie 1H-, 13C- und 15N-NMR-Daten.
An Efficient Cooperative Protocol for Multiuser-OFDM Networks (2006)

Abstract — In this paper, we propose a relay-based scheme where a fixed number of relays are utilized to design a OFDM cooperative protocol. By exploiting limited feedback from the destination such that each relay is able to help forward information of multiple sources in one OFDM symbol, the proposed cooperative protocol not only achieves full diversity but also efficiently utilizes available bandwidth. A practical relay assignment scheme is also proposed to specify the pairing of sources and relays in cooperative networks. The outage probability analysis of the proposed cooperative protocol is provided, and the analytical results are validated via computer experiments. Moreover, a closed-form lower bound on the outage probability of any relay-assignment schemes is established to provide a performance benchmark of the proposed cooperative protocol. Based on the outage probability analysis, the optimum relay location for the proposed relay-assignment scheme is determined. I.
Fault Propagation Analysis on the Transaction-Level Model of an Acquisition System with Bus Fallback Modes (2009)

The early fault analysis is mandatory for safety critical systems, which are required to operate safely even on the presence of faults. System design methodologies tackle the early design and verification of systems by allowing several abstraction for their models, but still offer only digital bit faults as fault models. Therefore we develop a signal fault model for the Transaction-Level Modeling. We extend the TLM generic payload by the signal characteristics: Voltage level, delay, slope time and glitches. In order to analyze and process these, a TLM bus model is created, with which signal faults can be detected and translated to data failures. Furthermore, inserting this bus in an acquisition system and implementing fallback modes for the bus operation, the propagation of the signal faults through the system can be assessed. Simulating this model using probability distributions for the different signal faults, 5516 faults have been generated. From these, 5143 have been recovered, 239 isolated and 134 turned into failures.
Medicinal inorganic chemistry: a web themed issue (2013)

A graphical abstract is available for this content
ASTM Unwashed Gum and the Propensity of a Fuel to Form Combustion Chamber Deposits (2000)

&lt;div class="htmlview paragraph"&gt;An investigative group set up under the auspices of the CEC (Coordinating European Council) collected data on combustion chamber deposits (CCD), ASTM unwashed gum (UWG) results and the thermogravimetric analysis (TGA) of these gums for different fuels from many different sources. The analysis of this data shows that UWG cannot and does not predict CCD. It is not possible to use UWG or any aspect of its behaviour in the TGA to assess the CCD-forming tendency of randomly chosen fuels.&lt;/div&gt;
Midfoot Fusion Technique for Neuroarthropathic Feet: Biomechanical Analysis and Rationale (1998)

To test the hypothesis that a plate applied to the plantar (tension) side of the medial midfoot provides stronger fixation than midfoot fusion with screw fixation, we biomechanically compared the two constructs for midfoot fusion. We created a model of midfoot instability in eight matched pairs of cadaver legs by section of joint capsule, ligaments, and tendons about Lisfranc's joints, and then performed a load-to-failure study to compare the fixation provided by a plantarly applied third tubular plate with that by cortical screws. After an initial load deformation curve to 1000 N was obtained, specimens were cyclically loaded at 200 to 750 N for 3000 cycles and then loaded to failure (screw pullout, fracture, or deformation >3 mm). Comparing the plantar plate and midfoot fusion with screw fixation constructs, a plate applied to the plantar (tension) aspect of the medial midfoot provides a stronger, sturdier construct than does midfoot fusion with screw fixation.
ChemInform Abstract: 2‐Siloxy‐4‐furanyl Anion: Remarkable Solvent Effect on Its Nucleophilicity. (2000)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Genome-Scale Metabolic Model of Xanthomonas phaseoli pv. manihotis: An Approach to Elucidate Pathogenicity at the Metabolic Level (2020)

<i>Xanthomonas phaseoli</i> pv. <i>manihotis</i> (<i>Xpm</i>) is the causal agent of cassava bacterial blight, the most important bacterial disease in this crop. There is a paucity of knowledge about the metabolism of <i>Xanthomonas</i> and its relevance in the pathogenic process, with the exception of the elucidation of the xanthan biosynthesis route. Here we report the reconstruction of the genome-scale model of <i>Xpm</i> metabolism and the insights it provides into plant-pathogen interactions. The model, iXpm1556, displayed 1,556 reactions, 1,527 compounds, and 890 genes. Metabolic maps of central amino acid and carbohydrate metabolism, as well as xanthan biosynthesis of <i>Xpm</i>, were reconstructed using Escher (https://escher.github.io/) to guide the curation process and for further analyses. The model was constrained using the RNA-seq data of a mutant of <i>Xpm</i> for quorum sensing (QS), and these data were used to construct context-specific models (CSMs) of the metabolism of the two strains (wild type and QS mutant). The CSMs and flux balance analysis were used to get insights into pathogenicity, xanthan biosynthesis, and QS mechanisms. Between the CSMs, 653 reactions were shared; unique reactions belong to purine, pyrimidine, and amino acid metabolism. Alternative objective functions were used to demonstrate a trade-off between xanthan biosynthesis and growth and the re-allocation of resources in the process of biosynthesis. Important features altered by QS included carbohydrate metabolism, NAD(P)<sup>+</sup> balance, and fatty acid elongation. In this work, we modeled the xanthan biosynthesis and the QS process and their impact on the metabolism of the bacterium. This model will be useful for researchers studying host-pathogen interactions and will provide insights into the mechanisms of infection used by this and other <i>Xanthomonas</i> species.
ChemInform Abstract: Synthesis of Z‐(Pinacolato)allylboron and Z‐(Pinacolato)alkenylboron Compounds Through Stereoselective Catalytic Cross‐Metathesis. (2013)

Abstract The authors describe three catalysts for the Z‐selective cross‐metathesis of allyl‐ and alkenylboron substrates.
Mechanistic Basis for the Iridium-Catalyzed Enantioselective Allylation of Alkenyl Boronates (2022)

Iridium(phosphoramidite) complexes catalyze an enantio- and diastereoselective three-component coupling reaction of alkenyl boronic esters, organolithium reagents, and secondary allylic carbonates. The reaction proceeds through an allylation-induced 1,2-metalate shift of the alkenyl boronate to form non-adjacent stereocenters. Mechanistic investigations outline the overall catalytic cycle and reveal trends in reactivity and selectivity. Analysis of relative stereochemistry in products derived from a variety of 1,1-disubtituted alkenyl boronates provides insight into the transition state of the addition and indicates a concerted pathway. Kinetic analysis of the reaction revealed the kinetic order dependence in boronate, the catalyst, and both the slow- and fast-reacting enantiomer of allylic carbonate as well as the turnover-limiting step of the reaction. Determination of nucleophile-specific parameters <i>N</i> and <i>s</i><sub>N</sub> for alkenyl boronate complexes enabled comparison to other classes of nucleophiles. DFT calculations indicate the addition of the alkenyl boronate to the cationic Ir(π-allyl) intermediate and the 1,2-metalate shift occur in a concerted mechanism. The stereoselectivity is determined by ligand-substrate steric repulsions and dispersion interactions in the <i>syn</i> addition transition state. Hammett studies supported the computational results with regard to electronic trends observed with both aryl-derived alkenyl boronates and aryl carbonates.
Editorial: Adhesive Dentistry in the Mirror of Excellent Research. (2021)

status: Published