gebhart/patrepeval huggingface dataset:
Discovery of a Potent, Orally Available, and Isoform-Selective Retinoic Acid β2 Receptor Agonist (2005)

4'-Octyl-4-biphenylcarboxylic acid (1g, AC-55649) was identified as a highly isoform-selective agonist at the human RARbeta2 receptor in a functional intact cell-based screening assay. The subsequent hit to lead optimization transformed the lipophilic, poorly soluble hit into a more potent and orally available compound (2, AC-261066) with retained beta2 selectivity and greatly improved physiochemical properties. Being an isoform-selective RARbeta2 receptor agonist that discriminates between nuclear receptor isoforms having identical ligand binding domains, 2 will be useful as a pharmacological research tool but also a valuable starting point for drug development.
ADDT: automatic data distribution tool for porting programs to PVM (1996)

An important issue facing users who develop applications on PVM is that of partitioning the data over the different processors and generating communication statements for non-local data accesses. The burden of generating communication statements is alleviated by data parallel languages like HPF. HPF requires the user to specify the distribution of the data in the application. This distribution is specified over the processors on which the application is to execute. A good data distribution depends on the number of processors, the communication latency and the underlying compilation system. We present a method for automatically generating a dynamic data distribution and alignments for a distributed memory environment. This method has been implemented in an automatic data distribution tool called ADDT. ADDT reads in a shared memory parallel program in Fortran and generates as output a HPF program. Our method works by breaking up the input program into sub parts called distribution blocks (DB). It then obtains a set of data distribution for the arrays in each DB using the data layouts from preceding DB's. The algorithms used to obtain a set of data distribution (called candidate distributions) for a DB are discussed. The final data layout for the program has to be selected from these candidate distributions. This selection is formulated as a linear optimization problem which minimizes the communication while minimizing loss of parallelism. We present experimental results obtained by running ADDT on some example programs.
Intelligent Image De‐Blurring for Imaging Flow Cytometry (2019)

By virtue of the combined merits of optical microscopy and flow cytometry, imaging flow cytometry is a powerful tool for rapid, high-content analysis of single cells in large heterogeneous populations. However, its efficiency (defined by the ratio of the number of clearly imaged cells to the total cell population) is not high (typically 50-80%), due to out-of-focus image blurring caused by imperfect fluidic focusing of cells, a common drawback that not only reduces the number of cell images useable for high-content analysis but also increases the probability of false events and missed rare cells. To address this challenge and expand the efficacy of imaging flow cytometry, here, we propose and demonstrate intelligent deblurring of out-of-focus cell images in imaging flow cytometry. Specifically, by using our machine learning algorithms, we show an 11% increase in variance and a 95% increase in first-order gradient summation of cell images taken with an optofluidic time-stretch microscope. Without strict hardware requirements, our intelligent de-blurring method provides a promising solution to the out-of-focus blurring problem of imaging flow cytometers and holds promise for significantly improving their performance. © 2019 International Society for Advancement of Cytometry.
A nonintrusive magnetically self-powered vibration sensor for automated condition monitoring of electromechanical machines (2016)

This paper presents a nonintrusive and electromagnetically self-powered embedded system with vibration sensor for condition monitoring of electromechanical machinery. This system can be installed inside the terminal block of a motor or generator and supports wireless communication for transferring data to a mobile device or computer for subsequent performance analysis. As an initial application, the sensor package is configured for automated condition monitoring of resiliently mounted machines. Upon detecting a spin-down event, e.g. a motor turnoff, the system collects and transmits vibration and residual backemf data as the rotor decreases in rotational speed. This data is then processed to generate an empirical vibrational transfer function (eVTF) rich in condition information for detecting and differentiating machinery and vibrational mount pathologies. The utility of this system is demonstrated via lab-based tests of a resiliently mounted 1.1 kW three-phase induction motor, with results showcasing the usefulness of the embedded system for condition monitoring.
Drug Delivery: Nanoparticles of Metal‐Organic Frameworks: On the Road to In Vivo Efficacy in Biomedicine (Adv. Mater. 37/2018) (2018)

In article number 1707365, Patrick Couvreur, Christian Serre, and co-workers evaluate the biomedical applications of metal–organic frameworks at the preclinical stage, for pharmacological applications or toxicity evaluation. Current surface-engineering approaches, in vivo studies, and their prospects are considered. The back cover image illustrates the circulation of drug-loaded MOF nanoparticles in a blood vessel. In particular, nanosized cages of MIL-100(Fe) loaded with Ibuprofen drug are represented. Cover project designed by Maria Mikołajczak-Zygmańska.
Learning Commonsense Knowledge Through Interactive Dialogue (2018)

One of the most difficult problems in Artificial Intelligence is related to acquiring commonsense knowledge - to create a collection of facts and information that an ordinary person should know. In this work, we present a system that, from a limited background knowledge, is able to learn to form simple concepts through interactive dialogue with a user. We approach the problem using a syntactic parser, along with a mechanism to check for synonymy, to translate sentences into logical formulas represented in Event Calculus using Answer Set Programming (ASP). Reasoning and learning tasks are then automatically generated for the translated text, with learning being initiated through question and answering. The system is capable of learning with no contextual knowledge prior to the dialogue. The system has been evaluated on stories inspired by the Facebook's bAbI's question-answering tasks, and through appropriate question and answering is able to respond accurately to these dialogues.
A Control Strategy to Avoid Drop and Inrush Currents during Transient Phases in a Multi-Transmitters DIPT System (2022)

Electrical Vehicles (EVs) have gained popularity in recent years in the automotive field. They are seen as a way to reduce the CO2 footprint of vehicles. Although EVs have witnessed significant advancement in recent years, they still have two major setbacks: limited autonomy and long recharging time. Dynamic Inductive Power Transfer (DIPT) systems permit charging EVs while driving, provide unlimited autonomy, and eliminate stationary charging time and lower battery dependency. Multiple transmitters are required to achieve DIPT; thus, dealing with transient phases is essential because every time a receiver crosses over from one transmitter to another, it experiences a new transient phase. This article presents a novel control strategy for multi-transmitter DIPT systems that ensures a continuous and stable power transfer to a moving EV. The proposed control strategy eliminates drop and inrush currents during transient phases. The control integrates a soft start feature and a degraded operating mode at a predefined maximum current value. The studied structure is a symmetrical series–series compensation network. Each transmitter coil is driven by a variable frequency inverter (around 85 kHz) to ensure Zero Phase Angle mode. The control strategy was numerically validated using MATLAB Simulink and then tested experimentally. Results show a relatively low power disruption after applying the proposed control during transmitter sequencing.
Life Extension of an X-Ray Tube Target (1998)

Abstract A methodology for the life extension of an X-Ray target was developed. X-Ray tube targets are rotating axisymmetric multi-component components used in X-Ray tubes of medical equipment. An X-Ray target is subjected to extreme cyclic thermal loading conditions based on the imaging system requirements. A very complex, time dependent stress state is present in such targets because of the combination of processing and utilization. Residual stresses are present following initial target assembly and heat treatment required to establish and maintain the high vacuum required in the X-Ray tube. In addition, cyclic stresses arise from the imaging protocols. The factors controlling these stresses include the thermal expansion coefficients of the various materials, the temperature distributions and the geometry of the components. The proposed methodology for the life extension of an X-Ray target included the development of an integrated thermal and structural axisymmetric finite element model. The combined thermal structural model was initially used to evaluate the severity of the various thermal protocols a target is subjected to. The structural analysis was carried out in the plastic regime, since typical stresses exceeded the yield stress of the materials used. Design of experiment (DOE) studies were carried out in order to evaluate the influence of geometric quantities on the resultant temperature distribution and thermal stresses. Tolerances of geometric quantities were applied to reflect manufacturing inaccuracies. An optimal design was selected for which the equivalent plastic strains were minimized. The effect of the manufacturing tolerances on the optimal solution was also examined.
Supplementary Figures 1-7, Tables 1-4 from AT13148 Is a Novel, Oral Multi-AGC Kinase Inhibitor with Potent Pharmacodynamic and Antitumor Activity (2023)

&lt;p&gt;PDF file - 553K, Supplementary Figure 1. Phosphorylation of AKT substrates remains suppressed, despite pSer473 AKT induction. Supplementary Figure 2. The pharmacokinetic-pharmacodynamic profile and antitumor activity of AT13148 in PTEN-deficient PC3 human prostate cancer xenografts. Supplementary Figure 3. Pharmacodynamic biomarker study of AT13148(40mg/kg) in MES-SA human tumor xenografts. Supplementary Figure 4. The antitumour activity of AT13148 in mutant KRAS A549 human lung cancer xenografts. Supplementary Figure 5. Mouse body weight data for the MES-SA (Figure 4B) and BT474 (Figure 4C) efficacy studies. Supplementary Figure 6. The effect of AT13148 versus CCT128930 on apoptosis and cell cycle distribution in U87MG human glioblastoma cells. Supplementary Figure 7. Differential effects of 24h treatment of 10M each of the AGC kinase inhibitor AT13148 and the selective AKT inhibitor CCT128930 on cell cycle effects in PTEN-deficient U87MG human glioblastoma cells. Supplementary Table 1. Summary of the inhibitory activity of 10��M AT13148 against in vitro. Supplementary Table 2. Summary of the inhibitory activity of AT13148 against a panel of protein kinases Supplementary Table 3. Summary of the in vitro cytotoxicity of AT13148 against a panel of human tumor cell lines harboring different defects in the PI3K-AKT signaling pathway. Supplementary Table 4. Summary of the pharmacokinetics of AT13148 in mouse plasma and tissues following iv or oral administration&lt;/p&gt;
Protein trafficking in Giardia lamblia (2003)

Giardia, a protozoan parasite of humans and other vertebrates, is a common cause of intestinal disease worldwide. Besides its medical importance, Giardia is considered an excellent system to study the evolution of fundamental cellular processes because it belongs to the earliest branches of the eukaryotic lineage of descent. Giardia trophozoites lack organelles typical of higher eukaryotes such mitochondria, peroxisomes and compartments involved in intracellular protein trafficking and secretion, such as the Golgi apparatus and secretory granules. Nevertheless, the minimal machinery for protein transport and sorting is present in this parasite. When Giardia undergoes encystation, the biogenesis of secretory organelles necessary to transport cyst wall constituents to the cell surface takes place. Recent studies in both vegetative and encysting trophozoites have provided interesting information regarding the secretory pathway of this important human pathogen.
923 PB 470 EFFECT OF HARVEST STAGE ON SOLIDS, ACIDS, FIRMNESS, AND SHELF-LIFE OF TOMATO (1994)

Fruit of 10 tomato (Lycopersicon esculentum Mill.) cultigens, including five typical fresh market F 1 's, two rin/ + F 1 's, two very firm (ultrafirm) inbreds, and an antisense PG F 1 , were harvested at mature green, breaker, and table ripe stages of development, passed over a grader and taken to a lab (21°C) for analyses of soluble solids, titratable acidity and firmness at the table ripe stage. Shelf life was also measured. Cultigens varied in response to both solids and acids at the three harvest stages, thus there was no clear effect of harvest stage on these variables. The rin /+ F 1 's and ultrafirm inbreds were significantly firmer than the other cultigens at the table ripe and breaker stages. Shelf life tended to decrease with maturity at harvest. One rin /+ F 1 had the greatest shelf life at all harvest stages. Ultrafirm and antisense PG cultigens had greater shelf life than the other six cultigens at the table ripe stage.
Effects of Single α-to-β Residue Replacements on Structure and Stability in a Small Protein: Insights from Quasiracemic Crystallization (2016)

Synthetic peptides that contain backbone modifications but nevertheless adopt folded structures similar to those of natural polypeptides are of fundamental interest and may provide a basis for biomedical applications. Such molecules can, for example, mimic the ability of natural prototypes to bind to specific target macromolecules but resist degradation by proteases. We have previously shown that oligomers containing mixtures of α- and β-amino acid residues ("α/β-peptides") can mimic the α-helix secondary structure, and that properly designed α/β-peptides can bind to proteins that evolved to bind to α-helical partners. Here we report fundamental studies that support the long-range goal of extending the α/β approach to tertiary structures. We have evaluated the impact of single α → β modifications on the structure and stability of the small and well-studied villin headpiece subdomain (VHP). The native state of this 35-residue polypeptide contains several α-helical segments packed around a small hydrophobic core. We examined α → β substitution at four solvent-exposed positions, Asn19, Trp23, Gln26 and Lys30. In each case, both the β(3) homologue of the natural α residue and a cyclic β residue were evaluated. All α → β(3) substitutions caused significant destabilization of the tertiary structure as measured by variable-temperature circular dichroism, although at some of these positions, replacing the β(3) residue with a cyclic β residue led to improved stability. Atomic-resolution structures of four VHP analogues were obtained via quasiracemic crystallization. These findings contribute to a fundamental α/β-peptide knowledge-base by confirming that β(3)-amino acid residues can serve as effective structural mimics of homologous α-amino acid residues within a natural tertiary fold, which should support rational design of functional α/β analogues of natural poly-α-peptides.
The Use of Semi-Solid Rheocasting (SSR) for Aluminum Automotive Castings (2003)

&lt;div class="htmlview paragraph"&gt;Semi-solid metal (SSM) casting has long been identified as a high-volume process for producing safety-critical and structural automotive castings, but cost and complexity issues have limited its widespread commercial acceptance. Rheocasting, an SSM process that creates semi-solid slurry directly from liquid metal, eliminates the cost disadvantages of the process. However, the majority of rheocasting processes are complex and difficult to operate in the foundry environment.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;Recent work at MIT has led to the fundamental discovery that application of heat removal and convection as a molten alloy cools through the liquidus creates a non-dendritic, semi-solid slurry. A new process based on this understanding, S.S.R.™ (Semi-Solid Rheocasting), simplifies the rheocasting process by controlling heat removal and convection of an alloy during cooling using an external device. Solution heat treatable castings have been produced in a horizontal die casting machine with the S.S.R.™ process. This paper discusses S.S.R.™ in greater detail and future applications of the process for the automotive industry.&lt;/div&gt;
Role of the N-terminal domain of the human DMC1 protein in octamer formation and DNA binding. VOLUME 280 (2005) PAGES 28382-28387 (2006)

PAGE 28385: Due to an inadvertent error, the wrong image was presented in Fig. 4C. Fig. 4C should appear as shown below. The figure legend and text remain unchanged.
Demonstration of scattering suppression in retardation-based plasmonic nanoantennas (2010)

Modifications in scattering strength of and local field enhancement by retardation-based plasmonic nanoantennas when being transformed from straight nanorods to split-ring resonators are investigated experimentally. Scattering properties are characterized with linear reflection and extinction spectroscopy of nanoantenna arrays, whereas local field enhancements are evaluated for individual nanoantennas using two-photon-excited photoluminescence (TPL) microscopy. The linear and nonlinear optical characterizations reveal that the optical response of nanoantennas is determined by the interference of counter-propagating short-range surface plasmon polaritons (SR-SPP) and that the transformation of nanorods into split-rings by bending significantly influences the scattering strength. Importantly, strong suppression of scattering for the fundamental SR-SPP resonance is observed when the bend radius is decreased, a feature that is attributed to the decrease in the nanoantenna electric-dipole response when bending the nanorods. The experimental observations are corroborated with numerical simulations using the finite-element method.
A non-canonical EZH2 function sensitizes solid tumors to genotoxic stress (2020)

Summary Drugs that block the activity of the methyltransferase EZH2 are in clinical development for the treatment of non-Hodgkin lymphomas harboring gain-of-function EZH2 mutations that enhance its polycomb repressive function. In contrast, in castration-resistant prostate cancer (CRPC) we have previously reported that EZH2 plays a non-canonical role as a transcriptional activator. In this setting, we now show that EZH2 inhibitors can also block the non-canonical activity of EZH2 and inhibit the growth of CRPC cells. Gene expression and epigenomic profiling of cells treated with EZH2 inhibitors demonstrated that rather than de-repressing tumor suppressor genes silenced by PRC2, EZH2 inhibitors downregulate a set of DNA repair genes that are directly regulated by EZH2. In addition, genome-wide CRISPR/Cas9-mediated loss-of-function screens in the presence of EZH2 inhibitors identified these DNA repair genes to underlie the growth-inhibitory function of these compounds. Interrogation of public data from diverse solid tumor types expressing wild-type EZH2 showed that expression of DNA damage repair genes is significantly correlated with cellular sensitivity to EZH2 inhibitors. Consistent with these findings, treatment of CRPC cells with EZH2 inhibitors dramatically enhanced their sensitivity to genotoxic stress. These studies reveal a previously unappreciated mechanism of action of EZH2 inhibitors and provide a mechanistic basis for potential new combination cancer therapies.
Incremental benefit of a novel signal recording system during mapping and ablation (2020)

Compared to current system, the PEP system provided incremental information including identifying conduction tissue signals, estimates of CF and a surrogate for lesion formation. This novel signal processing platform with increased DR and minimal front-end filtering may be useful in clinical practice.
In Vitro Calcium Antagonist Activity of Lercanidipine and Its Enantiomers (1997)

This study was undertaken to examine the in vitro calcium antagonist properties of lercanidipine and its enantiomers compared with nifedipine, nitrendipine, nicardipine, niguldipine, and amlodipine. Lercanidipine exhibited high affinity for the dihydropyridine (DHP) subunit of the L-type calcium channel, where it was much more potent than nifedipine and amlodipine. The (R)-enantiomer of lercanidipine was about 100-200-fold less potent than the (S)-one, indicating (S)-lercanidipine as the eutomer. Functional in vitro studies performed in isolated rat aorta preparations contracted by K+ demonstrated that lercanidipine and its enantiomers have a slower onset and cessation of calcium antagonist activity compared with other calcium antagonists. Inhibition of K+-induced contraction is due to the capacity of lercanidipine to interfere with Ca2+ homeostasis, as confirmed by parallel effects elicited by this compound on both muscle tone and [Ca2+]i elevation in guinea pig ileal longitudinal muscle. The slow onset and cessation of calcium antagonist activity of the compound, compared with nicardipine, was confirmed ex vivo studies in isolated rat aorta preparations taken fr?? rats orally treated with lercanidipine. In rat aortic str?? maintained at different degrees of depolarization during cubation with lercanidipine, functional calcium antagon activity was markedly increased by raising the tissue dep?? larization, and a potency ratio of 138 was found between t?? IC50 values evaluated at 5 and 100 mM K+. (S)-Lercani?? pine provided very similar results, whereas the (R)-enan?? omer activity did not appear to be affected by raising t?? tissue depolarization. The data reported here indicate th?? lercanidipine interferes with the L-type calcium chann?? where it reduces the inward calcium current, in a time- a?? voltage-dependent manner. This calcium antagonist effe?? has a gradual onset, is long-lasting, and can be mainly ?? lated to the (S)-enantiomer.