gebhart/patrepeval huggingface dataset:
Synthesis and dopamine agonist properties of (+)-trans-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-ol and its enantiomers (1990)

The dopamine agonist profile of (+-)-trans-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano [4,3-b]-1,4-oxazin-9-ol (16a) and its enantiomers (16b-c) was examined. Racemic 16a exhibited moderate affinity for the dopamine (DA) D2 receptor labeled with the DA antagonist ligand [3H]haloperidol and moderate in vivo activity; it attenuated gamma-butyrolactone-stimulated DA synthesis, decreased DA neuronal firing of substantia nigra DA neurons, and inhibited exploratory locomotor activity in rats, a profile consistent with a DA autoreceptor agonist mechanism of action. The (+)-enantiomer 16b possessed greater DA receptor affinity with the agonist ligand [3H]-N-propylnorapomorphine than with the antagonist ligand. In rats it potently inhibited DA synthesis and neuronal firing and also inhibited exploratory locomotion. The (-)-enantiomer, on the other hand, did not have significant activity in any of these tests. This profile indicates that like many other rigid DA agonists, the dopaminergic activity resides in one enantiomer, in this case the (+)-enantiomer 16b. On the basis of single-crystal X-ray analysis of a key intermediate, the absolute configuration of 16b was found to be 4aR, 10bR.
Therapeutic Targeting of Oncogenic Tyrosine Phosphatases (2017)

Protein tyrosine phosphatases (PTP) are exciting and novel targets for cancer drug discovery that work in concert with protein tyrosine kinases (PTK) in controlling cellular homeostasis. Given the activating role that some PTKs play in initiating growth factor-mediated cellular processes, PTPs are usually perceived as the negative regulators of these events and therefore tumor suppressive in nature. However, mounting evidence indicate that PTPs do not always antagonize the activity of PTKs in regulating tyrosine phosphorylation, but can also play dominant roles in the initiation and progression of signaling cascades that regulate cell functions. It follows, therefore, that PTP malfunction can actively contribute to a host of human disorders, in particular, cancer, metabolic syndromes, and autoimmune diseases. The Src homology domain containing phosphatase 2 (SHP2) and the three-membered family of phosphatases of regenerating liver (PRL) are infamously oncogenic members of the PTP superfamily. Both are established regulators of major cancer pathways such as Ras/ERK1/2, Src, JAK/STAT, JNK, NF-κB, and PTEN/PI3K/AKT. Furthermore, upregulation, mutation, or other dysregulation of these PTPs has been positively correlated with cancer initiation and progression. This review will provide topical coverage of target validation and drug discovery efforts made in targeting these oncogenic PTPs as compelling candidates for cancer therapy. <i>Cancer Res; 77(21); 5701-5. ©2017 AACR</i>.
Carbon capture in molten salts (2013)

Abstract Capture and storage of fossil carbon emitted to the atmosphere from anthropogenic sources has been identified as a key technology for keeping human‐induced global warming below 2°C. Available technologies have not achieved widespread impact due to costs related to increased energy consumption and expensive, large process equipment. Here, we show how molten inorganic halide salt‐based mixtures containing CaO may be utilized for selective capture and subsequent controlled release of carbon dioxide from diluted flue gases. Highly efficient absorption is demonstrated in a fluoride‐based liquid, absorbing close to 100% of the CO 2 from a simulated flue gas with an absorbing column height of only 10 cm. Greater than 90% carbonation with >80% regeneration to CaO was recorded. Excellent cyclability has been achieved with a chloride‐based liquid with 60% carbonation and 100% regeneration to CaO during four cycles. The high efficiencies may enable extraction of CO 2 from highly diluted gas mixtures.
Barium strontium titanate and non-ferroelectric oxide ceramic composites for use in phased array antennas (1995)

Abstract A ceramic ferroelectric phase shifting device has been demonstrated using Ba1−xSrxTiO3 (BSTO) ceramics. 1 As part of an effort to optimize the device performance, various composites of BSTO and other nonelectrically active oxide ceramics have been formulated. In general the composites have reduced dielectric constants, ε′, where ε = ε′-iε″ and reduced loss tangents, tan δ, compared to BSTO. The low dielectric constant and low loss tangent reduce the overall impedance mismatch and insertion loss of the device. In addition, the tunability (change in the dielectric constant with applied voltage) is maintained at a relatively high level (15% with an applied electric field of 1.5 V/μm) for dielectric constants of 200. The combination of electronic properties of these materials offer substantially higher operating frequencies, 10 GHz and above. The microstructures including grain size and phase analysis have been examined using SEM and EDX. X-ray diffraction has been used to identify the presence of any secondary phases formed in the composites. The analysis of the phase formation and compositional variations will be related to the electronic properties of the materials.
Towards next-generation alert management of data centers (2016)

The performance of today's enterprise IT systems depends upon the accurate generation of alerts to identify any anomalous behavior. Today's solutions however suffer from several shortcomings. The configurations are manual and do not adapt to any system changes. A large volume of redundant alerts are generated leading to inefficient resolution. Moreover, the generated alerts are reactive in nature and provide less time to take corrective actions. In this paper, we address the issues of setting the correct configurations, aggregating redundancies and generating proactive alerts. We demonstrate the effectiveness of our approach on a real-world case-study.
A metal halide high pressure discharge lamp with warm white colour and high efficacy (1979)

A Na, Tl, In, Sn high pressure discharge lamp of warm white colour was developed for an efficient energy utilization in indoor illumination. The lamp is characterised by: (1) low colour temperature (CCT = 3300 K) with good colour rendering (Ra = 85). (2) high luminous efficacy of approx. 90 lm/W, corresponding to the 5- to 6-fold of an incandescent lamp, (3) high life time of approx. 4000 h, corresponding to the 4-fold of an incandescent lamp, (4) arbitrary burning position as with an incandescent lamp. These data were achieved through utilization of strongly pressure broadened line radiation (Na, Tl, In) combined with molecular radiation (SnI, SnBr, HgI, HgBr). The main features of the lamp are discussed, in particular a deviation from local thermal equilibrium in the mantle of the discharge.
Widely tunable single-mode high power quantum cascade lasers (2011)

We demonstrate widely tunable high power distributed feedback quantum cascade laser array chips that span 190 nm and 200 nm from 4.4 um to 4.59 um and 4.5 um to 4.7 um respectively. The lasers emit single mode with a very narrow linewidth and side mode suppression ratio of 25 dB. Under pulsed operation power outputs up to 1.85 W was obtained from arrays with 3 mm cavity length and up to 0.95 W from arrays with 2 mm cavity length at room temperature. Continuous wave operation was also observed from both chips with 2 mm and 3 mm long cavity arrays up to 150 mW. The cleaved size of the array chip with 3 mm long cavities was around 4 mm x 5 mm and does not require sensitive external optical components to achieve wide tunability. With their small size and high portability, monolithically integrated DFB QCL Arrays are prominent candidates of widely tunable, compact, efficient and high power sources of mid-infrared radiation for gas sensing.
Acetylcholinesterase and butyrylcholinesterase activities in cerebrospinal fluid from different levels of the neuraxis of patients with dementia of the Alzheimer type. (1992)

Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities of cerebrospinal fluid (CSF) collected post mortem from the lateral ventricles, cisterna magna, and lumbar regions of the spinal cord of patients with a histologically confirmed diagnosis of Alzheimer's disease were compared with those of normal, age matched control patients, patients with dementia of non-Alzheimer aetiology, and patients with non-dementing neurological disorders. The AChE activity of the ventricular CSF of patients with Alzheimer's disease was 48% lower (p < 0.005) than that of age matched controls or patients with other types of dementia, and the AChE activity of CSF sampled from the basal cistern was 40% lower (p < 0.005) in patients with Alzheimer's disease. There were no significant differences between the AChE activity in Alzheimer's disease and control patients in CSF collected from the lumbar cistern. AChE activity was lower in CSF sampled from the basal and lumbar cistern of patients with dementia of non-Alzheimer aetiology, while ventricular activity was in the normal range. BuChE activity in ventricular CSF of Alzheimer's disease patients was 41% lower than normal (p < 0.05) and in the normal range in all other samples. The secretion of AChE from forebrain and hindbrain regions is reduced in Alzheimer's disease patients, leading to decreased ventricular and cisternal levels of the enzyme. Secretion from more caudal regions of the central nervous system seems to be unaffected by the disease, resulting in AChE in the lumbar CSF of patients with Alzheimer's disease being in the control range. Such altered secretion of AChE in the brain could have profound implications not only for cholinergic transmission in these patients but also for the proposed noncholinergic modulatory actions of AChE.
2-O-(β-<scp>d</scp>-Glucopyranosyl)ascorbic Acid, a Novel Ascorbic Acid Analogue Isolated from <i>Lycium</i> Fruit (2004)

A novel stable precursor of ascorbic acid (vitamin C), 2-O-(beta-D-glucopyranosyl)ascorbic acid, was isolated from both the ripe fresh fruit and dried fruit of Lycium barbarum L., a plant of the Solanaceae family. The chemical structure was inferred by instrumental analyses and confirmed by chemical synthesis. The dried fruit of Lycium barbarum L. contained ca. 0.5% of it, which is comparable to the ascorbic acid content of fresh lemons. It increased the blood ascorbic acid by oral administration to rats, and it was also detected in blood from the portal vein.
In vivo nuclear magnetic resonance chemical shift imaging by selective irradiation. (1984)

NMR images of preselected chemically shifted species can be obtained by selective irradiation of the remainder of the NMR chemical shift spectrum prior to application of a conventional NMR imaging sequence. The chemical-selective irradiation consists of narrow-bandwidth pi/2 or saturation radio-frequency pulses applied in the absence of imaging gradients. The technique permits substantial reductions in scan and reconstruction times over standard three- and four-dimensional Fourier transform chemical-shift-imaging methods, when images of few spectral peaks are desired. It is also suitable for the elimination of chemical shift artifacts in conventional high-field NMR imaging. In vivo applications of the technique to the head and limbs in a 1.5-T magnetic field yield 1H H2O and -CH2-images, with little detectable -CH2- in muscle and brain.
Calibration of a magnetometer array using motion capture equipment (2019)

Abstract This paper studies the problem of calibrating an array of single‐axis magnetometers in an unknown static inhomogeneous magnetic field using motion capture equipment. A proof of identifiability is given, practical identifiability of calibration parameters is established in simulation, and real world experiments are conducted to demonstrate the feasibility of this approach. Unlike many state of the art techniques, the proposed solution does not require a homogeneous field, as in fact, we demonstrate that an inhomogeneous field enlarges the set of identifiable parameters. Under the above‐mentioned assumptions, this approach may be used to extend self‐calibration techniques of visual‐inertial setups to magnetic sensor arrays in indoor environments.
GPR160 de-orphanization reveals critical roles in neuropathic pain in rodents (2020)

Treating neuropathic pain is challenging and novel non-opioid-based medicines are needed. Using unbiased receptomics, transcriptomic analyses, immunofluorescence, and in situ hybridization, we found that the expression of the orphan GPCR Gpr160 and GPR160 increased in the rodent dorsal horn of the spinal cord following traumatic nerve injury. Genetic and immunopharmacological approaches demonstrated that GPR160 inhibition in the spinal cord prevented and reversed neuropathic pain in male and female rodents without altering normal pain response. GPR160 inhibition in the spinal cord attenuated sensory processing in the thalamus, a key relay in the sensory discriminative pathways of pain. We also identified cocaine- and amphetamine-regulated transcript peptide (CARTp) as a GPR160 ligand. Inhibiting endogenous CARTp signaling in spinal cord attenuated neuropathic pain, whereas exogenous intrathecal CARTp evoked painful hypersensitivity through GPR160-dependent ERK and cAMP response element-binding protein (CREB). Our findings de-orphanize GPR160, identify it as a determinant of neuropathic pain and potential therapeutic target, and provide insights into its signaling pathways. CARTp is involved in many diseases including depression and reward and addiction; de-orphanization of GPR160 is a major step forward understanding the role of CARTp signaling in health and disease.
Phenyl Ether- and Aniline-Containing 2-Aminoquinolines as Potent and Selective Inhibitors of Neuronal Nitric Oxide Synthase (2015)

Excess nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) is implicated in neurodegenerative disorders. As a result, inhibition of nNOS and reduction of NO levels is desirable therapeutically, but many nNOS inhibitors are poorly bioavailable. Promising members of our previously reported 2-aminoquinoline class of nNOS inhibitors, although orally bioavailable and brain-penetrant, suffer from unfavorable off-target binding to other CNS receptors, and they resemble known promiscuous binders. Rearranged phenyl ether- and aniline-linked 2-aminoquinoline derivatives were therefore designed to (a) disrupt the promiscuous binding pharmacophore and diminish off-target interactions and (b) preserve potency, isoform selectivity, and cell permeability. A series of these compounds was synthesized and tested against purified nNOS, endothelial NOS (eNOS), and inducible NOS (iNOS) enzymes. One compound, 20, displayed high potency, selectivity, and good human nNOS inhibition, and retained some permeability in a Caco-2 assay. Most promisingly, CNS receptor counterscreening revealed that this rearranged scaffold significantly reduces off-target binding.
Theory and experimental verification of configurable computing with stochastic memristors (2021)

The inevitable variability within electronic devices causes strict constraints on operation, reliability and scalability of the circuit design. However, when a compromise arises among the different performance metrics, area, time and energy, variability then loosens the tight requirements and allows for further savings in an alternative design scope. To that end, unconventional computing approaches are revived in the form of approximate computing, particularly tuned for resource-constrained mobile computing. In this paper, a proof-of-concept of the approximate computing paradigm using memristors is demonstrated. Stochastic memristors are used as the main building block of probabilistic logic gates. As will be shown in this paper, the stochasticity of memristors' switching characteristics is tightly bound to the supply voltage and hence to power consumption. By scaling of the supply voltage to appropriate levels stochasticity gets increased. In order to guide the design process of approximate circuits based on memristors a realistic device model needs to be elaborated with explicit emphasis of the probabilistic switching behavior. Theoretical formulation, probabilistic analysis, and simulation of the underlying logic circuits and operations are introduced. Moreover, the expected output behavior is verified with the experimental measurements of valence change memory cells. Hence, it is shown how the precision of the output is varied for the sake of the attainable gains at different levels of available design metrics. This approach represents the first proposition along with physical verification and mapping to real devices that combines stochastic memristors into unconventional computing approaches.
Molecular cloning and sequence of partial cDNA for interferon-induced (2'-5')oligo(A) synthetase mRNA from human cells. (1983)

By using a translation assay in oocytes, a 17S RNA fraction coding for the interferon-induced (2'-5')oligo(A) synthetase was purified from human cells. A cDNA library was prepared by cloning in Escherichia coli plasmid pBR322 and screened by positive hybridization-translation in oocytes. A cDNA clone corresponding to the (2'-5')oligo(A) synthetase mRNA was identified. In SV80 cells, this E cDNA recognizes three RNAs of 1.65, 1.85, and 3.6 kilobases, which are present only after interferon treatment of the cells. In Namalva cells, mainly one RNA of 1.8 kilobases is seen.
Antitumor effects of OSU-2S, a nonimmunosuppressive analogue of FTY720, in hepatocellular carcinoma (2011)

Using the molecular platform of FTY720, we developed OSU-2S, a novel PKCδ-targeted antitumor agent, which is devoid of S1P1 receptor activity and is highly effective in suppressing HCC tumor growth in vivo. These findings suggest that OSU-2S has clinical value in therapeutic strategies for HCC and warrants continued investigation in this regard.
Hair growth effects of oral administration of finasteride, a steroid 5 alpha-reductase inhibitor, alone and in combination with topical minoxidil in the balding stumptail macaque. (1992)

A 5 alpha-reductase inhibitor, finasteride, was administered orally at 0.5 mg/day, alone or in combination with topical 2% minoxidil, for 20 weeks to determine the effects on scalp hair growth in balding adult male stumptail macaque monkeys. A 7-day dose-finding study showed that both 0.5- and 2.0-mg doses of the drug produced a similar diminution in serum dihydrotestosterone (DHT) in male stumptails. Hair growth was evaluated by shaving and weighing scalp hair at baseline and at 4-week intervals during treatment to obtain cumulative delta hair weight (sum of the 4-week changes in hair weight from baseline) for the 20-week study. The activity of the 5 alpha-reductase enzyme was assessed by RIA of serum testosterone (T) and DHT at 4-week intervals. The combination of finasteride and minoxidil generated significant augmentation of hair weight (additive effect) compared to either drug alone. Finasteride increased hair weight in four of five monkeys. When the data of the one nonresponsive monkey were excluded, finasteride elicited a significant elevation in hair weight compared to topical vehicle alone. Minoxidil also evoked a significant increase in hair weight compared to vehicle alone. Serum T was unchanged, whereas serum DHT was significantly depressed in monkeys that received either finasteride or the combination of finasteride and minoxidil. These data suggest that inhibition of the conversion of T to DHT by this 5 alpha-reductase inhibitor reverses the balding process and enhances hair regrowth by topical minoxidil in the male balding stumptail macaque.
A new FIFO design enabling fully-synchronous on-chip data communication network (2011)

A new FIFO design that enables fully synchronous circuits with unrelated clocks to communicate synchronously is proposed. Not only would every circuit be running on its own clock, but the interconnection network is fully synchronous and runs at an unrelated clock of its own. With relatively low gate count, the proposed FIFO allows communicating circuits to put/get data at their respective frequencies (1 datum/clock cycle) till it gets filled then the rates converge to the lower frequency. The maximum initial latency is 3 cycles of the consumer's clock. Several manifestations of the proposed FIFO have been developed for different design cases including data width mismatch between producer and consumer. The operation of different FIFOs has been verified using gate-level simulations for several ratios of clock frequencies. An 8-cell FIFO has been designed at the transistor-level and Spice simulations using a 0.13 μm, 1.2V technology has been carried out. It shows proper operation at producer and consumer clock frequencies of 2GHz and 3.125GHz, respectively, with a data transfer rate of more than 2Giga datum/second and an average power of 721 μW.
Design, Synthesis, and Crystal Structures of 6-Alkylidene-2′-Substituted Penicillanic Acid Sulfones as Potent Inhibitors of <i>Acinetobacter baumannii</i> OXA-24 Carbapenemase (2010)

Class D β-lactamases represent a growing and diverse class of penicillin-inactivating enzymes that are usually resistant to commercial β-lactamase inhibitors. As many such enzymes are found in multi-drug resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa, novel β-lactamase inhibitors are urgently needed. Five unique 6-alkylidene-2'-substituted penicillanic acid sulfones (1-5) were synthesized and tested against OXA-24, a clinically important β-lactamase that inactivates carbapenems and is found in A. baumannii. Based upon the roles Tyr112 and Met223 play in the OXA-24 β-lactamase, we also engineered two variants (Tyr112Ala and Tyr112Ala,Met223Ala) to test the hypothesis that the hydrophobic tunnel formed by these residues influences inhibitor recognition. IC(50) values against OXA-24 and two OXA-24 β-lactamase variants ranged from 10 ± 1 (4 vs WT) to 338 ± 20 nM (5 vs Tyr112Ala, Met223Ala). Compound 4 possessed the lowest K(i) (500 ± 80 nM vs WT), and 1 possessed the highest inactivation efficiency (k(inact)/K(i) = 0.21 ± 0.02 μM(-1) s(-1)). Electrospray ionization mass spectrometry revealed a single covalent adduct, suggesting the formation of an acyl-enzyme intermediate. X-ray structures of OXA-24 complexed to four inhibitors (2.0-2.6 Å) reveal the formation of stable bicyclic aromatic intermediates with their carbonyl oxygen in the oxyanion hole. These data provide the first structural evidence that 6-alkylidene-2'-substituted penicillin sulfones are effective mechanism-based inactivators of class D β-lactamases. Their unique chemistry makes them developmental candidates. Mechanisms for class D hydrolysis and inhibition are discussed, and a pathway for the evolution of the BlaR1 sensor of Staphylococcus aureus to the class D β-lactamases is proposed.
Tone Event Detection in Packet Telephony Using the StarCore™ SC140 Core (2004)

1 Tone Event Detection Basics 2 1.1 Tone Event Detector Architecture 2 1.2 Phase Detection With Frequency Offset Compensation 4 1.3 Summary of Theoretical Results 6 2 Tone Event Detector on StarCore 8 2.1 Automatic Level Control (ALC) 8 2.2 Tone Indication 9 2.3 Tone Indicator Counter 9 2.4 Finding the Closest Reference Frequency Tone .......10 2.5 FIR Filtering Implementation 10 3 Tone Events in Packet Telephony 11 4 RFC2833 Overview 11 4.1 Payload Format for Named Telephone Events .........12 4.2 Sending and Receiving Named Telephone Event Packets 15 4.3 Payload Format for Telephony Tones 16 4.4 Multiple Tones and Named Events in One Packet ...17 5 Conclusion 20 6 References 21 Tone Event Detection in Packet Telephony Using the StarCoreTM SC140 Core