gebhart/patrepeval huggingface dataset:
Structure–Activity Relationships of Pan-Gαq/11Coupled Muscarinic Acetylcholine Receptor Positive Allosteric Modulators (2018)

Recent years have seen a large increase in the discovery of allosteric ligands targeting muscarinic acetylcholine receptors (mAChRs). One of the challenges in screening such compounds is to understand their mechanisms of action and define appropriate parameter estimates for affinity, cooperativity and efficacy. Herein we describe the mechanisms of action and structure–activity relationships for a series of “pan-Gq-coupled” muscarinic acetylcholine (ACh) receptor (mAChR) positive allosteric modulators (PAMs). Using a combination of radioligand binding, functional inositol phosphate accumulation assays, receptor alkylation and operational data analysis, we show that most compounds in the series derive their variable potency and selectivity from differential cooperativity at the M1, M3 and M5 mAChRs. None of the PAMs showed greater than 10-fold subtype selectivity for the agonist-free receptor, but VU6007705, VU6007678, and VU6008555 displayed markedly increased cooperativity compared to the parent molecule and M5 mAChR-preferring PAM, ML380 (αβ > 100), in the presence of ACh. Most of the activity of these PAMs derives from their ability to potentiate ACh binding affinity at mAChRs, though VU6007678 was notable for also potentiating ACh signaling efficacy and robust allosteric agonist activity. These data provide key insights for the future design of more potent and subtype-selective mAChR PAMs.
Optically active catecholimidazolines: a study of steric interactions at .alpha.-adrenoreceptors (1983)

The optical isomers and deoxy form of 2-(3,4, alpha-trihydroxybenzyl)imidazoline hydrochloride were examined for their alpha-adrenergic activity on rat aorta. The rank order of stimulant activity was deoxy (2) congruent to (R)-(-)-1 greater than (S)-(+)-1. This is in contrast to catecholamines in which the order of activity is (R)-(-)-epinephrine greater than (S)-(+)-epinephrine = epinine (deoxyepinephrine). The relative order of potency for the isomers of 2-(3,4, alpha-trihydroxybenzyl)imidazoline is different than that predicted by the Easson--Stedman theory for stereoisomers of catecholamines. Also, substitution of the deoxy compound 2 with substituents, methyl or benzyl, in the 4-position lowers the alpha-adrenergic agonist activity, and differences observed between optical isomers were small.
Brønsted Acid Catalyzed Tandem Defunctionalization of Biorenewable Ferulic acid and Derivates into Bio‐Catechol (2019)

Abstract An efficient conversion of biorenewable ferulic acid into bio‐catechol has been developed. The transformation comprises two consecutive defunctionalizations of the substrate, that is, C−O (demethylation) and C−C (de‐2‐carboxyvinylation) bond cleavage, occurring in one step. The process only requires heating of ferulic acid with HCl (or H 2 SO 4 ) as catalyst in pressurized hot water (250 °C, 50 bar N 2 ). The versatility is shown on a variety of other (biorenewable) substrates yielding up to 84 % di‐ (catechol, resorcinol, hydroquinone) and trihydroxybenzenes (pyrogallol, hydroxyquinol), in most cases just requiring simple extraction as work‐up.
Feedback Control Over Noisy Channels: Characterization of a General Equilibrium (2021)

In this article, we study an energy-regulation tradeoff that delineates the fundamental performance bound of a feedback control system over a noisy channel in an unreliable communication regime. The channel and the process are modeled by an additive white Gaussian noise channel with fading and a partially observable Gauss–Markov process, respectively. Moreover, the feedback control loop is constructed by designing an encoder with a scheduler and a decoder with a controller. The scheduler and the controller are the decision makers deciding about the transmit power and the control input at each time, respectively. Associated with the energy-regulation tradeoff, we characterize an equilibrium at which neither the scheduler nor the controller has a unilateral incentive to deviate from its policy. We argue that this equilibrium is a general one as it attains global optimality without any restrictions on the information structure or the policy structure, despite the presence of signaling and dual effects.
The Shutdown Problem: How Does a Blockchain System End? (2019)

We define and examine the shutdown problem for blockchain systems: how to gracefully end the system's operation at the end of its useful life. A particular focus is those blockchain systems that hold archival data of long-lived interest. We outline what it means to achieve a successful shutdown, and compare those criteria to likely end-of-life conditions in a generic blockchain system. We conclude that the decentralized nature of blockchain systems makes shutdown difficult, particularly if the system uses an unstable consensus like the Nakamoto consensus of Bitcoin. Accordingly, we recommend against using blockchain with unstable consensus for any data whose value is likely to persist beyond the life of the blockchain system. For any such systems that are already in operation, we recommend considering a hard fork to implement stable consensus. Such consideration needs to happen well in advance of the system's end of life.
Olfactory function in patients with postinfectious and posttraumatic smell disorders before and after treatment with vitamin A: A double‐blind, placebo‐controlled, randomized clinical trial (2012)

The systemic application of vitamin A at a dose of 10,000 IU per day for 3 months does not appear to be useful in the treatment of postinfectious or posttraumatic olfactory loss.
ChemInform Abstract: Reactions of Carbonyl Compounds with Benzyl Chloromethyl Ether of Diiodomethane in the Presence of Samarium(II) Iodide or Metallic Samarium. New Routes to 1,2‐Diols, Iodohydrins and Cyclopropanols. (1992)

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.
Five‐minute knee MRI for simultaneous morphometry and T2 relaxometry of cartilage and meniscus and for semiquantitative radiological assessment using double‐echo in steady‐state at 3T (2017)

2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1328-1341.
SiC protective coating for photovoltaic retinal prosthesis (2016)

SiC coatings demonstrating no erosion in accelerated aging test for 112 d at 87 °C, equivalent to about 10 years in vivo, can offer effective protection of the implants. Photovoltaic retinal prostheses with PECVD SiC coatings exhibited effective protection from erosion during the 4 month follow-up in vivo. The optimal thickness of SiC layers is about 560 nm, as defined by anti-reflective properties and by sufficient coverage to eliminate defects.
Viscosity Measurements of Very Thin Polymer Films (2005)

We have measured the viscosity of thin polymer films on Si substrates using three independent, yet complementary techniques: bilayer dewetting measurements where the viscosity of the lower layer is derived from the opening velocity of dewetting holes in the more viscous upper layer, X-ray photon correlation spectroscopy (XPCS) where the viscosity of a single layer is determined from the relaxation rate of thermally induced surface roughness, and dynamic secondary ion mass spectroscopy (DSIMS) where the viscosity is derived from measurements of the tracer diffusion coefficient. The scaling relationship, η ∼ MwPSα, yielded α = 3.3 ± 0.3 and α = 3.2 ± 0.1 from dewetting and XPCS measurement, respectively, which was in excellent agreement with the bulk scaling of 3.4 and the prediction from reptation theory. The absolute magnitudes were consistently higher by at most a factor of 3 than the bulk values, except for the sample studied at lower temperatures (155−170 °C) using XPCS. The temperature dependence in each case was weaker than the bulk values. These effects were interpreted in terms of attractive interactions with the Si surface which confined the polymer chains and affected the dynamics near the interface.
Hydrogenation of 3-Methyl-3-buten-1-yl Acetate to Alcohols in the Presence of Bimetallic Cu˗Pt Catalysts (2022)

The catalytic synthesis of isoprenol by hydrogenation of 3-methylbut-3-en-1-yl acetate on heterogeneous bimetallic Cu-Pt catalysts was carried out for the first time. The best selectivity of isoprenol (76%) was obtained on the 5%Cu–1%Pt/SiO2 catalyst with a full ester conversion in 6 h of the reaction.
Intelligent whole-blood imaging flow cytometry for simple, rapid, and cost-effective drug-susceptibility testing of leukemia (2019)

Drug susceptibility (also called chemosensitivity) is an important criterion for developing a therapeutic strategy for various cancer types such as breast cancer and leukemia. Recently, functional assays such as high-content screening together with genomic analysis have been shown to be effective for predicting drug susceptibility, but their clinical applicability is poor since they are time-consuming (several days long), labor-intensive, and costly. Here we present a highly simple, rapid, and cost-effective liquid biopsy for ex vivo drug-susceptibility testing of leukemia. The method is based on an extreme-throughput (>1 million cells per second), label-free, whole-blood imaging flow cytometer with a deep convolutional autoencoder, enabling image-based identification of the drug susceptibility of every single white blood cell in whole blood within 24 hours by simply flowing a drug-treated whole blood sample as little as 500 μL into the imaging flow cytometer without labeling. Our results show that the method accurately evaluates the drug susceptibility of white blood cells from untreated patients with acute lymphoblastic leukemia. Our method holds promise for affordable precision medicine.
Properties of Water-Soluble Porphyrin as a Sensitizer in Peroxyoxalate-Hydrogen Peroxide Chemiluminescence System and Its Application to the Quenching FluorometriC Determination of Copper(II) (2000)

ABSTRACT Six kinds of water-soluble porphyrin were examined as a sensitizer (fluorophore) in the bis(2,4,6-trichlorophenyl)oxalate(TCPO)-hydrogen peroxide (H2O2) chemiluminescence(CL) system. Among them, coproporphyrin III showed the highest CL intensity. Moreover, the TCPO-H2O2-coproporphyrin III CL system was separately examined in each micelle solution using a non-ionic surfactant such as Briji 35 and Triton X-100, and an ionic surfactant such as cetyltrimethylammonium chloride(CTAC) and sodium dodecylsulfate. As a result, the CL intensity along with the coexistence of the CTAC micelle increased approximately 36 times compared to that in the absence of surfactant. Based on these findings, the quenching CL determination of copper(II) was established using the complex formation of coproporphyrin III and copper(II) ion. The calibration graph for the concentration of copper(II) was linear in the range of 2×10−8M to 1×10−6M, and the detection limit(3σ) was 1.26×10−8M. Moreover, the relative standard deviation was 2.9%(10 determinations). The proposed method was applied to the determination of copper(II) ion in waste water and satisfactory results were obtained. Key Words: peroxyoxalate-hydrogen peroxide chemiluminescencefluorophorewater-soluble porphyrincoproporphyrin IIIdetermination of copper(II)
A Hybrid ARQ Scheme for Resilient Packet Header Compression (2006)

In this work we address resilient packet header compression in a setup similar to RFC 3095 (robust header compression - ROHC), where a noisy feedback channel is available. We propose a new predictive hybrid ARQ (HARQ), using a systematic convolutional code with delay-limited interleaving. The compressed packet headers are bit interleaved, encoded, and the parity bits are loaded onto the packets in a manner that is consistent with existing standards. Our HARQ design is distinct from previous ones in that it cannot wait until the end of a codeword for retransmission, rather, ARQ's corresponding to individual packet headers arrive continually during a convolutional codeword and must be processed at that time. In our system, each time a NACK is encountered, the encoder estimates the state of the Viterbi decoder, deciding when a retransmission is necessary. The use of coding in conjunction with a specially designed interleaver, provides a flexible and powerful design methodology that makes it possible to improve the throughput via FEC and interleaving, while strictly limiting the delay to avoid timeout in higher layers. Simulations show that the throughput of the resulting system is superior to ROHC, and the delay is less sensitive to the channel conditions. Furthermore, over a large part of the operating range the delay is comparable to, or smaller than, the delay of RQHC
An on-line algorithm for checkpoint placement (2002)

Checkpointing is a common technique for reducing the time to recover from faults in computer systems. By saving intermediate states of programs in a reliable storage device, checkpointing enables one to reduce the processing time loss caused by faults. The length of the intervals between the checkpoints affects the execution time of the programs. Long intervals lead to a long re-processing time, while too-frequent checkpointing leads to a high checkpointing overhead. In this paper, we present an online algorithm for the placement of checkpoints. The algorithm uses online knowledge of the current cost of a checkpoint when it decides whether or not to place a checkpoint. We show how the execution time of a program using this algorithm can be analyzed. The total overhead of the execution time when the proposed algorithm is used is smaller than the overhead when fixed intervals are used. Although the proposed algorithm uses only online knowledge about the cost of checkpointing, its behavior is close to that of the off-line optimal algorithm that uses the complete knowledge of the checkpointing cost.
Activation and Oxidation of Mesitylene C–H Bonds by (Phebox)Iridium(III) Complexes (2015)

A pincer iridium(III) complex, (Phebox)Ir(OAc)2OH2 (1) (Phebox = 3,5-dimethylphenyl-2,6-bis(oxazolinyl)), selectively cleaves the benzylic C–H bond of mesitylene to form an isolable iridium mesityl complex, (Phebox)Ir(mesityl)(OAc) (3), in >90% yield. The trifluoroacetate analogue, (Phebox)Ir(OCOCF3)2OH2 (2), was synthesized to compare with complex 1 for C–H activation, and (Phebox)Ir(mesityl)(OCOCF3) (4) was synthesized by ligand exchange of complex 3. Both complexes 1 and 2 catalyze H/D exchange between mesitylene and D2O at 180 °C, exclusively at the benzylic position; 2 gave a higher turnover number (11 TO) than 1 (6 TO) in 12 h. Using d4-acetic acid as the source of deuterium, up to 92 turnovers of benzylic H/D exchange of mesitylene were obtained with complex 1. (Phebox)Ir(OCOCF3)2OH2 catalyzed the benzylic C–H oxidation of mesitylene using Ag2O as a terminal oxidant at 130 °C, to form 3,5-dimethylbenzaldehyde and 3,5-dimethylbenzoic acid in 35% ± 4% yield (5.1 ± 0.6 TO). DFT calculations were used to investigate two possible pathways for the catalytic oxidation of mesitylene: (1) C–H activation followed by oxy-functionalization and (2) Ir-oxo formation followed by outer-sphere C–H hydroxylation. Results of calculations of the C–H activation pathway appear to be the more consistent with the experimental observations.
Vesicourethral anastomosis using a novel telesurgical system with haptic sensation, the Telelap Alf-X: a pilot study. (2014)

Vesicourethral anastomosis is a necessary part of radical prostatectomy and presents technical challenges when performed endoscopically. This study demonstrates the feasibility of the van Velthoven anastomosis method in swine model using a novel telesurgical system with haptic sensation: the Telelap Alf-X. Twenty vesicourethral anastomoses were performed using the system in female swine with two working ports and a camera. With two 2.0 Vicryl, a single knot vesicourethral anastomosis was performed as described by van Velthoven with Telelap Alf-X. The time of each operation was recorded, water tightness and tension were examined at the end of the procedure by irrigation through a 12 Fr catheter. The 1:1 haptic sensation, improved ergonomy, the open architecture of the robotic system, and articulated handles contributed to the easiness of performance and short learning curve, as the time of the procedure decreased by 50% after the first 5 cases. All the anastomoses were functional and proved to be successful and watertight. No leakage occurred. The novel features of the Telelap Alf-X contribute to its ease of use and make the telesurgical performance of vesicourethral anastomosis similar to open surgery, without the disadvantages of the latter.
Multi-objective Optimization of Double D Coils for Wireless Charging System (2018)

This paper proposes a multi-objective optimization method of the primary double D coils for wireless charging system based on Non-dominated sorting genetic algorithms II (NSGA-II). The optimization result provides several useful design rules are concluded regarding how the dimensions of both coil and ferrite layer affect the coupling and leakage. A practical coil for wireless charging level 2 defined by the SAE J2954 is used as the reference and as the starting point for the optimization. Finally, one of the coil structure from the optimization result is chosen for validation using finite element method.
PRISM: topologically constrained phased refinement for macromolecular crystallography (1993)

We describe the further development of phase refinement by iterative skeletonization (PRISM), a recently introduced phase-refinement strategy [Wilson & Agard (1993). Acta Cryst. A49, 97-104] which makes use of the information that proteins consist of connected linear chains of atoms. An initial electron-density map is generated with inaccurate phases derived from a partial structure or from isomorphous replacement. A linear connected skeleton is then constructed from the map using a modified version of Greer's algorithm [Greer (1985). Methods Enzymol. 115, 206-226] and a new map is created from the skeleton. This 'skeletonized' map is Fourier transformed to obtained new phases, which are combined with any starting-phase information and the experimental structure-factor amplitudes to produce a new map. The procedure is iterated until convergence is reached. In this paper significant improvements to the method are described as is a challenging molecular-replacement test case in which initial phases are calculated from a model containing only one third of the atoms of the intact protein. Application of the skeletonization procedure yields an easily interpretable map. In contrast, application of solvent flattening does not significantly improve the starting map. The iterative skeletonization procedure performs well in the presence of random noise and missing data, but requires Fourier data to at least 3.0 A. The constraints of linearity and connectedness prove strong enough to restore not only missing phase information, but also missing amplitudes. This enables the use of a powerful statistical test, analogous to the 'free R factor' of conventional refinement [Brünger (1992). Nature (London), 355, 472-474], for optimizing the performance of the skeletonization procedure. In the accompanying paper, we describe the application of the method to the solution of the structure of the protease inhibitor ecotin bound to trypsin and to a single isomorphous replacement problem.
Temperature and frequency dependence of the velocity of sound in dielectric crystals (1967)

Abstract The temperature and frequency dependence of the velocity of sound in dielectric crystals have been calculated to lowest order in anharmonic terms by using the quasi-harmonic approximation and the phonon Boltzmarm equation. It is assumed that the quasi-harmonic approximation for the stress in a deformed crystal in microscopic equilibrium may be generalized to non-equilibrium situations in a simple way. It is found that at very low frequencies the velocity is determined by the adiabatic elastic constants in agreement with classical continuum theory. At high frequencies, however, the classical isothermal result is not obtained, and in contrast to the classical result it is found that there is a change in velocity in going from low frequencies to high frequencies for pure shear waves. A rough estimate is made of the magnitude of this effect and it is decided that it should be observable under suitable conditions.
Abstract 4609: Novel phosphorylation and ubiquitination sites regulate ROS-dependent degradation of c-FLIP and sensitization of cancer cells to TRAIL. (2013)

Abstract The cytosolic protein c-FLIP (cellular Fas-associated death domain-like interleukin 1β-converting enzyme inhibitory protein) is an inhibitor of death receptor-mediated apoptosis that is up-regulated in a variety of cancers, contributing to apoptosis resistance. Several compounds found to restore sensitivity of cancer cells to TRAIL, a TNF family death ligand with promising therapeutic potential, act by targeting c-FLIP ubiquitination and degradation by the proteasome. The generation of reactive oxygen species (ROS) has been implicated in c-FLIP protein degradation. However, the mechanism by which ROS post-transcriptionally regulate c-FLIP protein levels is not well understood. We show here that treatment of prostate cancer PPC-1 cells with the superoxide generators menadione or paraquat down-regulates c-FLIP long (c-FLIPL) protein levels, which is prevented by the proteasome inhibitor MG132. Furthermore, pretreatment of PPC-1 cells with a ROS scavenger prevented ubiquitination and loss of c-FLIPL protein induced by menadione or paraquat. We identified lysine 167 as a novel ubiquitination site of c-FLIPL important for ROS-dependent degradation. We also identified threonine 166 as a novel phosphorylation site and demonstrate that T166 phosphorylation is required for ROS-induced K167 ubiquitination. The mutation of either T166 or K167 was sufficient to stabilize c-FLIP protein levels in PPC-1, HEK293T, and HeLa cancer cells treated with menadione or paraquat. Accordingly, expression of c-FLIP T166A or K167R mutants protected cells from ROS-mediated sensitization to TRAIL-induced cell death. Our findings reveal novel ROS-dependent post-translational modifications of c-FLIP that regulate c-FLIP protein degradation and subsequent sensitization of cancer cells to TRAIL. Citation Format: Rachel P. Wilkie-Grantham, Shu-Ichi Matsuzawa, John C. Reed. Novel phosphorylation and ubiquitination sites regulate ROS-dependent degradation of c-FLIP and sensitization of cancer cells to TRAIL. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4609. doi:10.1158/1538-7445.AM2013-4609