gebhart/patrepeval huggingface dataset:
Targeting the Large Subunit of Human Ribonucleotide Reductase for Cancer Chemotherapy (2011)

Ribonucleotide reductase (RR) is a crucial enzyme in de novo DNA synthesis, where it catalyses the rate determining step of dNTP synthesis. RRs consist of a large subunit called RR1 (α), that contains two allosteric sites and one catalytic site, and a small subunit called RR2 (β), which houses a tyrosyl free radical essential for initiating catalysis. The active form of mammalian RR is an α(n)β(m) hetero oligomer. RR inhibitors are cytotoxic to proliferating cancer cells. In this brief review we will discuss the three classes of RR, the catalytic mechanism of RR, the regulation of the dNTP pool, the substrate selection, the allosteric activation, inactivation by ATP and dATP, and the nucleoside drugs that target RR. We will also discuss possible strategies for developing a new class of drugs that disrupts the RR assembly.
Toward Ionic-Liquid-Based Model Catalysis: Growth, Orientation, Conformation, and Interaction Mechanism of the [Tf2N]− Anion in [BMIM][Tf2N] Thin Films on a Well-Ordered Alumina Surface (2010)

Aiming at a better understanding of the interaction of ionic liquid (IL) thin films with oxide supports, we have performed a model study under ultrahigh vacuum (UHV) conditions. We apply infrared reflection absorption spectroscopy (IRAS) in combination with density functional theory (DFT). Thin films of 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [BMIM][Tf(2)N] are grown on an atomically flat, well-ordered alumina film on NiAl(110) using a novel UHV-compatible evaporator. Time-resolved IRAS measured during the growth and subsequent thermal desorption points toward reversible molecular adsorption and desorption. There was no indication of decomposition. The vibrational bands are assigned with the help of DFT calculations. Strong relative intensity changes in individual [Tf(2)N](-) bands are observed in the monolayer region. This indicates pronounced orientation effects for the anion. The adsorption geometry of [Tf(2)N](-) is determined on the basis of a detailed comparison with DFT. The results suggest that [Tf(2)N](-) anions adopt a cis conformation in the submonolayer region. They adsorb in a slightly tilted orientation with respect to the surface, mainly interacting with the support via the sulfonyl groups.
Entanglement-Enhanced Interferometry in Optical Fiber (2021)

Fiber-based interferometry with entangled photons can provide sub-shot-noise resolution, which is ideal for photon-starved applications. Simulations demonstrate that measurements with realistic losses and other imperfections show quantum-enhanced phase resolution for practical applications.
Nonlinear Dynamics of MEMS Arches Under Harmonic Electrostatic Actuation (2010)

We present an investigation of the nonlinear dynamics of clamped-clamped micromachined arches when actuated by a dc electrostatic load superimposed on an ac harmonic load. The Galerkin method is used to discretize the distributed-parameter model of a shallow arch to obtain a reduced-order model. The static response of the arch due to a dc load actuation is simulated, and the results are validated by comparing them to experimental data. The dynamic response of the arch to a combined dc load and ac harmonic load is studied when excited near its fundamental natural frequency, twice its fundamental natural frequency, and near other higher harmonic modes. The results show a variety of interesting nonlinear phenomena, such as hysteresis, softening behavior, dynamic snap-through, and dynamic pull-in. The results are also shown demonstrating the potential to use microelectromechanical systems (MEMS) arches as bandpass filters and low-powered switches. An experimental work is conducted to test arches realized of curved polysilicon microbeams when excited by dc and ac loads. Experimental data are shown for the softening behavior and the dynamic pull-in of the curved microbeams.
Establishment of Normal Gut Microbiota Is Compromised under Excessive Hygiene Conditions (2011)

The results documented here indicate that establishment and development of the normal gut microbiota requires continuous microbial exposure during the early stages of life and this process is compromised under conditions of excessive hygiene.
Slingshot homolog-1–mediated Nrf2 sequestration tips the balance from neuroprotection to neurodegeneration in Alzheimer’s disease (2023)

Oxidative damage in the brain is one of the earliest drivers of pathology in Alzheimer's disease (AD) and related dementias, both preceding and exacerbating clinical symptoms. In response to oxidative stress, nuclear factor erythroid 2-related factor 2 (Nrf2) is normally activated to protect the brain from oxidative damage. However, Nrf2-mediated defense against oxidative stress declines in AD, rendering the brain increasingly vulnerable to oxidative damage. Although this phenomenon has long been recognized, its mechanistic basis has been a mystery. Here, we demonstrate through in vitro and in vivo models, as well as human AD brain tissue, that Slingshot homolog-1 (SSH1) drives this effect by acting as a counterweight to neuroprotective Nrf2 in response to oxidative stress and disease. Specifically, oxidative stress-activated SSH1 suppresses nuclear Nrf2 signaling by sequestering Nrf2 complexes on actin filaments and augmenting Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 interaction, independently of SSH1 phosphatase activity. We also show that <i>Ssh1</i> elimination in AD models increases Nrf2 activation, which mitigates tau and amyloid-β accumulation and protects against oxidative injury, neuroinflammation, and neurodegeneration. Furthermore, loss of <i>Ssh1</i> preserves normal synaptic function and transcriptomic patterns in tau<sup>P301S</sup> mice. Importantly, we also show that human AD brains exhibit highly elevated interactions of Nrf2 with both SSH1 and Keap1. Thus, we demonstrate here a unique mode of Nrf2 blockade that occurs through SSH1, which drives oxidative damage and ensuing pathogenesis in AD. Strategies to inhibit SSH1-mediated Nrf2 suppression while preserving normal SSH1 catalytic function may provide new neuroprotective therapies for AD and related dementias.
Machine Learning Identifies Chemical Characteristics That Promote Enzyme Catalysis (2019)

Despite tremendous progress in understanding and engineering enzymes, knowledge of how enzyme structures and their dynamics induce observed catalytic properties is incomplete, and capabilities to engineer enzymes fall far short of industrial needs. Here, we investigate the structural and dynamic drivers of enzyme catalysis for the rate-limiting step of the industrially important enzyme ketol-acid reductoisomerase (KARI) and identify a region of the conformational space of the bound enzyme-substrate complex that, when populated, leads to large increases in reactivity. We apply computational statistical mechanical methods that implement transition interface sampling to simulate the kinetics of the reaction and combine this with machine learning techniques from artificial intelligence to select features relevant to reactivity and to build predictive models for reactive trajectories. We find that conformational descriptors alone, without the need for dynamic ones, are sufficient to predict reactivity with greater than 85% accuracy (90% AUC). Key descriptors distinguishing reactive from almost-reactive trajectories quantify substrate conformation, substrate bond polarization, and metal coordination geometry and suggest their role in promoting substrate reactivity. Moreover, trajectories constrained to visit a region of the reactant well, separated from the rest by a simple hyperplane defined by ten conformational parameters, show increases in computed reactivity by many orders of magnitude. This study provides evidence for the existence of reactivity promoting regions within the conformational space of the enzyme-substrate complex and develops methodology for identifying and validating these particularly reactive regions of phase space. We suggest that identification of reactivity promoting regions and re-engineering enzymes to preferentially populate them may lead to significant rate enhancements.
Interleukin-5: Modulator of innate and acquired immunity (2005)

The interleukin-5 (IL-5)-IL-5-receptor system has been of great interest because the IL-5-receptor (IL-5R) contains the common cytokine-receptor β-chain (βc), which is shared with the GM-CSF receptor and IL-3 receptor. IL-5 is produced by type 2 T helper cells (Th2), mast cells, and eosinophils, and non-hematopoietic cells. As we discuss, IL-5 has pleiotropic actions, from enhancing the homeostatic proliferation and survival of B-1 cells through noncognate stimulation and driving the differentiation of B-1 and B-2 cells into terminally differentiated plasma cells to augmenting the survival and activation of eosinophils. Thus, IL-5 links natural and adaptive immunity specific to the epitopes of natural ligands and exogenous antigens leading to the inducion of Ig-producing cells, regulating chronic inflammation and controlling disease. The potential roles of IL-5 in immune responses, allergy and autoimmunity make it attractive candidate for use in the clinical setting.
ChemInform Abstract: Approaches to the Preparation of Enantiomerically Pure (2R,2′R)‐(+)‐threo‐Methylphenidate Hydrochloride (2001)

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.
5G Experimental Trial Achieving over 20 Gbps Using Advanced Multi-Antenna Solutions (2016)

We propose a trial concept that utilizes advanced multi-antenna solutions such as beamforming and spatial multiplexing with a massive number of antenna elements for use in a previously established trial system for the fifth generation (5G) mobile broadband communications system. Furthermore, we present experimental results showing that multi-user aggregated data rates exceeding 20 Gbps are possible in a real field environment.
Achieving low TN effluent by operating AvN control coupled with partial denitrification-anammox control (2018)

Achieving low TN effluent by operating AvN control coupled with partial denitrification-anammox control Author(s): Tri LeRahil FofanaArash MassoudiehAhmed Al-OmariSudhir MurthyBernhard WettKartik ChandranChristine DeBarbadilloCharles BottHaydée De ClippeleirSourceProceedings of the Water Environment FederationSubjectMainstream Innovations in Nitrogen RemovalDocument typeConference PaperPublisherWater Environment FederationPrint publication date Jan, 2018ISSN1938-6478SICI1938-6478(20180101)2018:5L.153;1-DOI10.2175/193864718824940222Volume / Issue2018 / 5Content sourceNutrient Removal and Recovery SymposiumFirst / last page(s)153 - 156Copyright2018Word count166Subject keywordsshort-cut N removalNOB out-selectionmainstream deammonification
Phosphorylation of the Platelet p47 Phosphoprotein Is Mediated by the Lipid Products of Phosphoinositide 3-Kinase (1995)

Platelet stimulation by thrombin or the thrombin receptor activating peptide (TRAP) results in the activation of phosphoinositide 3-kinase and the production of the novel polyphosphoinositides phosphatidylinositol 3,4-bisphosphate (PtdIns-3,4-P2) and phosphatidylinositol 3,4,5-trisphosphate (PtdIns-3,4,5-P3). We have shown previously that these lipids activate calcium-independent protein kinase C (PKC) isoforms in vitro (Toker, A., Meyer, M., Reddy, K. K., Falck, J. R., Aneja, R., Aneja, S., Parra, A., Burns, D. J., Ballas, L. M. and Cantley, L. C. (1994) J. Biol. Chem. 269, 32358-32367). Activation of platelet PKC in response to TRAP is detected by the phosphorylation of the major PKC substrate in platelets, the p47 phosphoprotein, also known as pleckstrin. Here we provide evidence for two phases of pleckstrin phosphorylation in response to TRAP. A rapid phase of pleckstrin phosphorylation (< 1 min) precedes the peak of PtdIns-3,4-P2 production and is unaffected by concentrations of wortmannin (10-100 nM) that block production of this lipid. However prolonged phosphorylation of pleckstrin (> 2 min) is inhibited by wortmannin concentrations that block PtdIns-3,4-P2 production. Phorbol ester-mediated pleckstrin phosphorylation was not affected by wortmannin and wortmannin had no effect on purified platelet PKC activity. Phosphorylation of pleckstrin could be induced using permeabilized platelets supplied with exogenous gamma-32P[ATP] and synthetic dipalmitoyl PtdIns-3,4,5-P3 and dipalmitoyl PtdIns-3,4-P2 micelles, but not with dipalmitoyl phosphatidylinositol 3-phosphate or phosphatidylinositol 4,5-bisphosphate. These results suggest two modes of stimulating pleckstrin phosphorylation: a rapid activation of PKC (via diacylglycerol and calcium) followed by a slower activation of calcium-independent PKCs via PtdIns-3,4-P2.
A Simple Spacer Technique to Fabricate Poly-Si TFTs With 50-nm Nanowire Channels (2007)

In this letter, polycrystalline-silicon thin-film transistors (poly-Si TFTs) with 50-nm nanowire (NW) channels, which are fabricated without advanced photolithography by using a sidewall spacer-formation technique, are proposed for the first time. Because the polygate electrode is perpendicularly across poly-Si NW channels to form a trigatelike structure, the proposed poly-Si NW TFT owns outstanding gate controllability. In summary, a simple and low-cost scheme is proposed to fabricate high-performance poly-Si NW TFT suitable for future display manufacturing and practical applications.
A Fiber-Based Sensing Array for Persistent Ocean Monitoring (2022)

Undersea applications involving acoustic propagation often require continual knowledge of the sound speed at different depths. Existing systems that collect sound velocity profile data have a limited lifetime. To address this need, we are developing long-length, fiber sensing arrays that can persistently monitor water characteristics. Here, we describe the process used to fabricate these fibers, as well as a custom technique for integrating electronics into the fiber. An application specific integrated circuit (ASIC) was designed and fabricated for handling long-distance communication along the fiber. A proof-of-concept demonstration was performed in the ocean where temperature was measured for 3 hours and compared to a reference temperature probe. The fiber sensing array presented here offers a lightweight, low-power system for persistent monitoring of the ocean.
Engine data classification with simultaneous recurrent network using a hybrid pso-ea algorithm (2006)

We applied an architecture which automates the design of simultaneous recurrent network (SRN) using a new evolutionary learning algorithm. This new evolutionary learning algorithm is based on a hybrid of particle swarm optimization (PSO) and evolutionary algorithm (EA). By combining the searching abilities of these two global optimization methods, the evolution of individuals is no longer restricted to be in the same generation, and better performed individuals may produce offspring to replace those with poor performance. The novel algorithm is then applied to the simultaneous recurrent network for the engine data classification. The experimental results show that our approach gives solid performance in categorizing the nonlinear car engine data.
3-D Imaging Using Millimeter-Wave 5G Signal Reflections (2021)

Emerging 5G millimeter-wave (mm-wave) networks use electronic beamforming and beamsteering and support signal bandwidths on the order of hundreds of MHz. Given these characteristics, opportunities exist to develop 3-D sensing applications that leverage 5G mm-wave communications infrastructure. In this context, this work introduces a signal processing pipeline that can: 1) accurately extract the Time of Flight (ToF) of reflected orthogonal frequency division multiplexing (OFDM) communications signals and 2) enhance range resolution by coherently aggregating the reflection information from separate frequency bands. In combination with precise beamsteering, the proposed signal processing techniques enable high-resolution 3-D radar imaging without affecting communications protocols. An experimental system demonstrating this concept has been implemented and is described. This system consists of two software-defined phased array radios (SDPARs), one configured as a prototype 5G base station TX, and one as an auxiliary prototype 5G RX. Each SDPAR primarily consists of a Si-based 28-GHz, 64-element, phased array transceiver module and software-defined radio. Simulation and benchmark results show that our coherent bandwidth stitching enables accurate OFDM-based ranging with 15-cm resolution. Measurement results show 3-D radar images of indoor scenes with 2° angular and 15-cm ranging resolution, created by processing reflected 5G-like communication waveforms at 28 GHz. The produced 3-D radar images effectively depict the location of objects in the scene, and these locations are in close agreement with the ground truth.
Telomerase reactivation in leukemia cells (1996)

We utilized fluorescent-labeled primers and modified the telomeric repeal amplification protocol (TRAP) to assess telomerase activity during the process of in vitro establishment in four different leukemia cell lines. We demonstrate that three of four leukemia cell lines had elevated telomerase activity, shortened telomeres, and the appearance of either dicentric chromosomes or acentric fragments. By contrast, one leukemia cell line (HAL-01) had high levels of telomerase activity, stable telomeres, but no obvious additional cytogenetic rearrangements. These experiments indicate that there may be several pathways involving telomerase activity in the establishment of leukemia cell lines.
Lovastatin induces COX-2 and PGE2 in immortalized human bronchial epithelial cells. (2006)

Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006

B81 

Purpose Statins are attractive candidates in the treatment and prevention of lung tumors, since lung cancer and atherosclerosis share several important risk factors including smoking and advanced age. Cyclooxygenase 2 (COX-2) inhibition, while effective in the prevention of colon cancer recurrence, has been associated with an increased incidence of myocardial infarction. Thus, there is a rationale for combined prevention of lung cancer with statins and COX-2 inhibitors. Methods We utilized Human Immortalized Bronchial Epithelial Cells (HBEC) and HBEC with K-rasV12 mutations (HBEC-Kras). We treated cells with lovastatin at concentrations of 1-5μM, and celecoxib at doses of 1-2.5μM. Mevalonolactone 250uM treatment was utilized for specific reversal of HMG-CoA reductase inhibition. 24-72 hours following treatment, we assayed proliferation by MTT assays, PGE2 levels by competitive ELISA and COX-2 mRNA and protein levels by Western Blot and RT-PCR. Results HBEC-Kras cells demonstrated markedly elevated PGE2, COX-2 mRNA and COX-2 protein levels compared to HBEC cells. Lovastatin markedly reduced the proliferation of both HBEC and HBEC-Kras cells. We hypothesized that lovastatin treatment would reduce the PGE2 and COX-2 levels in these cell lines. Surprisingly, 48 hours of lovastatin treatment markedly increased PGE2 levels in both cell lines. Statins induced higher PGE2 levels in HBEC-Kras cells compared to HBEC cells. This induction was lovastatin concentration dependent, and reversible with mevalonate. We found that the lovastatin mediated elevation of PGE2 levels was first detectable at 48hrs and increased at 72hrs, suggesting a specific, sterol-mediated mechanism. Lovastatin increased COX-2 mRNA and protein levels in a dose and time dependent manner. The COX-2 mRNA and protein levels were higher at every dose and time in HBEC-Kras cells compared to HBEC. Finally, we investigated the impact of lovastatin and celecoxib in combination on cell proliferation. We found that celecoxib alone had no anti-proliferative effect, whereas combination treatment reduced cell proliferation greater than lovastatin alone. Conclusion Lovastatin induces the production of PGE2, COX-2 mRNA and COX-2 protein in a concentration, sterol and time dependent manner, in HBEC and HBEC-Kras cells. Celecoxib and lovastatin in combination have an augmented anti-proliferative effect than either drug alone. While the importance and mechanism of lovastatin mediated COX-2 induction is under investigation, the combination of these agents warrants further study.
Frequency-Swept Integrated and Stretched Solid Effect Dynamic Nuclear Polarization (2018)

We investigate a new time domain approach to dynamic nuclear polarization (DNP), the frequency-swept integrated solid effect (FS-ISE), utilizing a high power, broadband 94 GHz (3.35 T) pulse EPR spectrometer. The bandwidth of the spectrometer enabled measurement of the DNP Zeeman frequency/field profile that revealed two dominant polarization mechanisms, the expected ISE, and a recently observed mechanism, the stretched solid effect (S<sup>2</sup>E). At 94 GHz, despite the limitations in the microwave chirp pulse length (10 μs) and the repetition rate (2 kHz), we obtained signal enhancements up to ∼70 for the S<sup>2</sup>E and ∼50 for the ISE. The results successfully demonstrate the viability of the FS-ISE and S<sup>2</sup>E DNP at a frequency 10 times higher than previous studies. Our results also suggest that these approaches are candidates for implementation at higher magnetic fields.
Virulence Dynamics and Breeding for Resistance to Stripe, Stem, and Leaf Rust in Canada Since 2000 (2019)

Wheat (<i>Triticum</i> spp.) is a major field crop in Canada in terms of acreage, annual production, and export market value. There are nine classes of Canadian wheat based on growth habit (winter or spring), kernel hardness (hard or soft), seed coat color (red or white), and quality factors (grain protein content and gluten strength). Wheat was described by Newman in 1928 as "the economic fairy to the industrial and commercial life of Canada, having built practically the whole economic structure of the Prairie Provinces." Wheat production in Canada is affected by several biotic and abiotic stresses. The major abiotic stresses are frost damage, drought, and heat stress. Among biotic stresses, diseases caused by fungal pathogens are the most important although wheat streak mosaic virus (WSMV) has caused some localized outbreaks in some years. In context of cultivar registration in Canada, there are certain diseases that breeders have to take into account while developing resistant cultivars. The Prairie Recommending Committee for Wheat, Rye, and Triticale (PRCWRT) classify wheat diseases into priority one, priority two, and priority three depending on prevalence and potential damage they can cause. However, priority one diseases are more of a concern and a minimum level of resistance in commercial cultivars is recommended for those.
Over 1500 V/2 A operation of GaN RESURF-MOSFETs on sapphire substrate (2009)

A GaN reduced surface field (RESURF) metal oxide semiconductor (MOSFET) on a sapphire substrate is fabricated. The n−-type RESURF zone was formed by a Si ion implantation technique. The n+- and n−-type GaN was activated at 1260°C for 30 s in ambient Ar. The sheet carrier densities (activation ratio) of n+- and n−-GaN were ∼3.0×1015 (∼100%) and 1.1×1012 cm−2 (1.8%), respectively. As a result, more than 1500 V and 2 A operation of the GaN RESURF MOSFETs is achieved with a channel length of 4 µm, a channel width of 150 mm, and the RESURF length of 20 µm.
A Practical Criterion for the Rapid Detection of Single‐Loop and Double‐Loop Reentry Tachycardias (2012)

The proposed criterion can diagnose single- and double-loop reentry atrial tachycardia using intracardiac recordings from any pair of well separated positions. The criterion does not require precise electrode placement or extensive activation mapping.