gebhart/patrepeval huggingface dataset:
A genome-wide meta-analysis uncovers six sequence variants conferring risk of vertigo (2021)

Vertigo is the leading symptom of vestibular disorders and a major risk factor for falls. In a genome-wide association study of vertigo (N<sub>cases</sub> = 48,072, N<sub>controls</sub> = 894,541), we uncovered an association with six common sequence variants in individuals of European ancestry, including missense variants in ZNF91, OTOG, OTOGL, and TECTA, and a cis-eQTL for ARMC9. The association of variants in ZNF91, OTOGL, and OTOP1 was driven by an association with benign paroxysmal positional vertigo. Using previous reports of sequence variants associating with age-related hearing impairment and motion sickness, we found eight additional variants that associate with vertigo. Although disorders of the auditory and the vestibular system may co-occur, none of the six genome-wide significant vertigo variants were associated with hearing loss and only one was associated with age-related hearing impairment. Our results uncovered sequence variants associating with vertigo in a genome-wide association study and implicated genes with known roles in inner ear development, maintenance, and disease.
Inside Cover: Gold(I)‐Catalyzed Alkoxyhalogenation of β‐Hydroxy‐α,α‐Difluoroynones (Angew. Chem. Int. Ed. 41/2008) (2008)

Gold(I) catalysts teamed with selectfluor produce trifluorinated dihydropyranones from difluoroynones under mild conditions, as described by V. Gouverneur et al. in the Communication on page 7927 ff. The process proceeds via a vinylgold intermediate that undergoes fluorination and competing protonation. This gold chemistry is encouraging for the synthesis of architecturally complex fluorinated targets combining fluorinated precursors with electrophilic fluorinating reagents. The illustration was produced by Dr. Karl Harrison (University of Oxford)
Data from β-Catenin mRNA Silencing and MEK Inhibition Display Synergistic Efficacy in Preclinical Tumor Models (2023)

&lt;div&gt;Abstract&lt;p&gt;Colorectal carcinomas harbor well-defined genetic abnormalities, including aberrant activation of Wnt/β-catenin and MAPK pathways, often simultaneously. Although the MAPK pathway can be targeted using potent small-molecule drugs, including BRAF and MEK inhibitors, β-catenin inhibition has been historically challenging. RNAi approaches have advanced to the stage of clinical viability and are especially well suited for transcriptional modulators, such as β-catenin. In this study, we report therapeutic effects of combined targeting of these pathways with pharmacologic agents. Using a recently described tumor-selective nanoparticle containing a β-catenin–targeting RNAi trigger, in combination with the FDA-approved MEK inhibitor (MEKi) trametinib, we demonstrate synergistic tumor growth inhibition in &lt;i&gt;in vivo&lt;/i&gt; models of colorectal cancer, melanoma, and hepatocellular carcinoma. At dose levels that were insufficient to significantly impact tumor growth as monotherapies, combination regimens resulted in synergistic efficacy and complete tumor growth inhibition. Importantly, dual MEKi/RNAi therapy dramatically improved survival of mice bearing colorectal cancer liver metastases. In addition, pharmacologic silencing of β-catenin mRNA was effective against tumors that are inherently resistant or that acquire drug-induced resistance to trametinib. These results provide a strong rationale for clinical evaluation of this dual-targeting approach for cancers harboring Wnt/β-catenin and MAPK pathway mutations. &lt;i&gt;Mol Cancer Ther; 17(2); 544–53. ©2017 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Development of a Mathematical Model for Physical Disintegration of Flushable Consumer Products in Wastewater Systems (2009)

The processes that flushable solid products may undergo after discharge to wastewater systems are (1) physical disintegration of solids resulting from turbulence, (2) direct dissolution of water-soluble components, (3) hydrolysis of solids to form soluble components, and (4) biodegradation of soluble and insoluble components. We develop a mathematical model for physical disintegration of flushable solid consumer products and test it with two different flushable products--product A, which has 40% water soluble-content, and product B, which has no water-soluble components. We present our modeling analysis of experimental results, from which we computed disintegration rate constants and fractional distribution coefficients for the disintegration of larger solids. The rate constants for solids of product A in units of (hour(-1)) are 0.45 for > 8-mm, 2.25 x 10(-2) for 4- to 8-mm, 0.9 x 10(-2) for 2- to 4-mm, and 1.26 x 10(-2) for 1- to 2-mm solids. The rate constants for solids of product B in units of hour(-1) are 1.8 for > 8-mm, 1.8 for 4- to 8-mm, 3.6 x 10(-1) for 2- to 4-mm, and 2.25 x 10(-3) for 1- to 2-mm solids. As indicated by the rate constants, larger solids disintegrate at a faster rate than smaller solids. In addition, product B disintegrated much faster and went mostly to the smallest size range, while product A disintegrated more slowly and was transferred to a range of intermediate solid sizes.
<scp>Nfu</scp> facilitates the maturation of iron‐sulfur proteins and participates in virulence in <scp><i>S</i></scp><i>taphylococcus aureus</i> (2014)

The acquisition and metabolism of iron (Fe) by the human pathogen Staphylococcus aureus is critical for disease progression. S. aureus requires Fe to synthesize inorganic cofactors called iron-sulfur (Fe-S) clusters, which are required for functional Fe-S proteins. In this study we investigated the mechanisms utilized by S. aureus to metabolize Fe-S clusters. We identified that S. aureus utilizes the Suf biosynthetic system to synthesize Fe-S clusters and we provide genetic evidence suggesting that the sufU and sufB gene products are essential. Additional biochemical and genetic analyses identified Nfu as an Fe-S cluster carrier, which aids in the maturation of Fe-S proteins. We find that deletion of the nfu gene negatively impacts staphylococcal physiology and pathogenicity. A nfu mutant accumulates both increased intracellular non-incorporated Fe and endogenous reactive oxygen species (ROS) resulting in DNA damage. In addition, a strain lacking Nfu is sensitive to exogenously supplied ROS and reactive nitrogen species. Congruous with ex vivo findings, a nfu mutant strain is more susceptible to oxidative killing by human polymorphonuclear leukocytes and displays decreased tissue colonization in a murine model of infection. We conclude that Nfu is necessary for staphylococcal pathogenesis and establish Fe-S cluster metabolism as an attractive antimicrobial target.
Glutamine metabolism via glutaminase 1 in autosomal-dominant polycystic kidney disease (2017)

These findings provide support that alteration in glutamine metabolism may play a role in cyst growth. However, testing in other models of PKD and identification of the compensatory metabolic changes that bypass GLS1 inhibition will be critical to validate GLS1 as a drug target either alone or when combined with inhibitors of other metabolic pathways.
Status of the Australian Consortium for Interferometric Gravitational Astronomy (2000)

We report progress on the development of gravitational wave research facilities by the Australian Consortium for Interferometric Gravitational Astronomy (ACIGA) and significant R&D advances across the four major subsystems related to an interferometric gravitational wave detector: configurations; lasers and optics; isolation, suspension and thermal noise; and data analysis.
Aerodynamic Characteristics of a Centrifugal Compressor Working in Supercritical Carbon Dioxide (2012)

Development of a closed cycle gas turbine with supercritical carbon dioxide as a working fluid is underway to generate power from low-range or intermediate-range waste heat sources. A demonstration test using a reduced scale turbomachine was conducted and the aerodynamic characteristics of a compressor were examined. A compressor was selected as centrifugal with 30 mm outer diameter and rated rotational speed of 1.7 kHz and mass flow rate of 1.2 kg/s. To reduce compression work, the operating condition at the inlet to compressor was chosen in a supercritical state close to the critical point of 7.38 MPa, 304 K where the compressibility coefficient z becomes markedly small and real gas effect dominant. The experimental range in terms of z is 0.16<z<0.6. The measured pressure ratio and adiabatic efficiency of the compressor are compared with calculations conducted using the Meanline method. The compressor performance in the supercritical liquid-like phase becomes highest in the experiment, which is well simulated by the method. The calculated pressure ratio shows excellent matching with experimental data in the supercritical liquid-like phase. However overestimation is recognized at the off-design point in the supercritical gaslike or subcritical region. Experiments also show that the compressor performance improves with reduction of the compressibility coefficient, which the Meanline method has well predicted.
CoNNeCT Baseband Processor Module (2011)

A document describes the CoNNeCT Baseband Processor Module (BPM) based on an updated processor, memory technology, and field-programmable gate arrays (FPGAs). The BPM was developed from a requirement to provide sufficient computing power and memory storage to conduct experiments for a Software Defined Radio (SDR) to be implemented. The flight SDR uses the AT697 SPARC processor with on-chip data and instruction cache. The non-volatile memory has been increased from a 20-Mbit EEPROM (electrically erasable programmable read only memory) to a 4-Gbit Flash, managed by the RTAX2000 Housekeeper, allowing more programs and FPGA bit-files to be stored. The volatile memory has been increased from a 20-Mbit SRAM (static random access memory) to a 1.25-Gbit SDRAM (synchronous dynamic random access memory), providing additional memory space for more complex operating systems and programs to be executed on the SPARC. All memory is EDAC (error detection and correction) protected, while the SPARC processor implements fault protection via TMR (triple modular redundancy) architecture. Further capability over prior BPM designs includes the addition of a second FPGA to implement features beyond the resources of a single FPGA. Both FPGAs are implemented with Xilinx Virtex-II and are interconnected by a 96-bit bus to facilitate data exchange. Dedicated 1.25- Gbit SDRAMs are wired to each Xilinx FPGA to accommodate high rate data buffering for SDR applications as well as independent SpaceWire interfaces. The RTAX2000 manages scrub and configuration of each Xilinx.
A Regulatory Role for Sphingolipids in Neuronal Growth (1995)

Sphingolipids, particularly gangliosides, are enriched in neuronal membranes where they have been implicated as mediators of various regulatory events. We recently provided evidence that sphingolipid synthesis is necessary to maintain neuronal growth by demonstrating that in hippocampal neurons, inhibition of ceramide synthesis by Fumonisin B1 (FB1) disrupted axonal outgrowth (Harel, R. and Futerman, A. H. (1993) J. Biol. Chem. 268, 14476-14481). We now analyze further the relationship between neuronal growth and sphingolipid metabolism by examining the effect of an inhibitor of glucosylceramide synthesis, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1- propanol (PDMP) and by examining the effects of both FB1 and PDMP at various stages of neuronal development. No effects of FB1 or PDMP were observed during the first 2 days in culture, but by day 3 axonal morphology was significantly altered, irrespective of the time of addition of the inhibitors to the cultures. Cells incubated with FB1 or PDMP had a shorter axon plexus and less axonal branches. FB1 appeared to cause a retraction of axonal branches between days 2 and 3, although long term incubation had no apparent effect on neuronal morphology or on the segregation of axonal or dendritic proteins. In contrast, incubation of neurons with conduritol B-epoxide, an inhibitor of glucosylceramide degradation, caused an increase in the number of axonal branches and a corresponding increase in the length of the axon plexus. A direct correlation was observed between the number of axonal branch points per cell and the extent of inhibition of either sphingolipid synthesis or degradation. These results suggest that sphingolipids play an important role in the formation or stabilization of axonal branches.
Isolated frequencies at which nonlinear materials behave linearly (2019)

In this Rapid Communication, we demonstrate that specific frequencies in weakly nonlinear lattices avoid the generation of higher harmonics, and thus the lattices behave linearly. Using a multiple scales analysis, we present plane-wave solutions that persist at only a single frequency and wave number; i.e., whose spatiotemporal production of higher harmonics is remarkably small. We study monatomic and diatomic chains with quadratic and cubic stiffness nonlinearities as example systems. Direct numerical integration of the equations of motion confirms that finite amplitude plane waves assigned to these special frequencies produce negligible higher harmonics when injected into the lattices. Such findings provide new considerations for the operating frequency of nonlinear communications devices, sensors, and transducers for enhanced signal-to-noise ratios.
Comparison of the 1.85 Å structure of CYP154A1 from <i>Streptomyces coelicolor</i> A3(2) with the closely related CYP154C1 and CYPs from antibiotic biosynthetic pathways (2003)

The genus Streptomyces produces two-thirds of microbially derived antibiotics. Polyketides form the largest and most diverse group of these natural products. Antibiotic diversity of polyketides is generated during their biosynthesis by several means, including postpolyketide modification performed by oxidoreductases, a broad group of enzymes including cytochrome P450 monooxygenases (CYPs). CYPs catalyze site-specific oxidation of macrolide antibiotic precursors significantly affecting antibiotic activity. Efficient manipulation of Streptomyces CYPs in generating new antibiotics will require identification and/or engineering of monooxygenases with activities toward a diverse array of chemical substrates. To begin to link structure to function of CYPs involved in secondary metabolic pathways of industrially important species, we determined the X-ray structure of Streptomyces coelicolor A3(2) CYP154A1 at 1.85 A and analyzed it in the context of the closely related CYP154C1 and more distant CYPs from polyketide synthase (EryF) and nonribosomal peptide synthetase (OxyB) biosynthetic pathways. In contrast to CYP154C1, CYP154A1 reveals an active site inaccessible from the molecular surface, and an absence of catalytic activities observed for CYP154C1. Systematic variations in the amino acid patterns and length of the surface HI loop correlate with degree of rotation of the F and G helices relative to the active site in CYP154A1-related CYPs, presumably regulating the degree of active site accessibility and its dimensions. Heme in CYP154A1 is in a 180 degrees flipped orientation compared with most other structurally determined CYPs.
Application of a Circularly Polarized Metaline to Beam-Steerable Antennas (2018)

Circularly polarized (CP) metaline beam-steerable antennas are presented. First, the unit cell for a CP metaline is designed such that the dispersion diagram, DD, is close to the DD for a linearly polarized conventional CRLH transmission line. Second, a planar 4X-metaline system where four CP metalines are horizontally arrayed in the shape of a cross is discussed. The 4X-metaline system maintains the same antenna characteristics when the beam is rotated around the antenna axis by changing the location of the activated feed point. The steered beam has a deviation of 1.22 dB from the omnidirectionality. Third, the number of the CP metalines is increased to eight (planar 8X-metaline system). The 8X-metaline system has a gain that is 2.15 dB greater than that for the 4X-metaline system. Finally, a non-planar system designated as the pillar 4X-metaline system is discussed, where four CP metalines are vertically arrayed on the surface of a pillar. A quasi-omnidirectional pattern with a deviation of 1.98 dB is observed.
A Nonlinear Model Predictive Control Strategy with a Disturbance Observer for Spark Ignition Engines with External EGR (2017)

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;This research proposes a control system for Spark Ignition (SI) engines with external Exhaust Gas Recirculation (EGR) based on model predictive control and a disturbance observer. The proposed Economic Nonlinear Model Predictive Controller (E-NMPC) tries to minimize fuel consumption for a number of engine cycles into the future given an Indicated Mean Effective Pressure (IMEP) tracking reference and abnormal combustion constraints like knock and combustion variability. A nonlinear optimization problem is formulated and solved in real time using Sequential Quadratic Programming (SQP) to obtain the desired control actuator set-points. An Extended Kalman Filter (EKF) based observer is applied to estimate engine states, combining both air path and cylinder dynamics. The EKF engine state(s) observer is augmented with disturbance estimation to account for modeling errors and/or sensor/actuator offset. The complete control system demonstrates strong disturbance rejection and closed loop stability. RMS error of IMEP reference tracking is 1.1% for engine cycles without active combustion constraints. Mean computation time for the proposed control system is 1.07 ms in the rapid-prototype engine controller, suggesting it is feasible for future ECUs. The proposed model predictive engine control strategy actively compensates for air path delay, resulting in higher EGR percentage and reduced combustion phasing retard as compared to conventional engine control strategies. FTP drive cycle simulation results of both conventional map-based engine control and the proposed E-NMPC on the same engine model suggest approximately 6.5% of fuel economy improvement.&lt;/div&gt;&lt;/div&gt;
Design and Structural Analysis of Novel Pharmacophores for Potent and Selective Peroxisome Proliferator-activated Receptor γ Agonists (2009)

Utilizing medicinal chemistry design strategies such as benzo splitting and ring expansion, we converted PPARalpha/gamma dual agonist 1 to selective PPARgamma agonists 19 and 20. Compounds 19 and 20 were 2- to 4-fold better than rosiglitazone at PPARgamma receptor, with 80- to 100-fold PPARgamma selectivity over PPARalpha receptor. X-ray cocrystal studies in PPARgamma and modeling studies in PPARalpha give molecular insights for the improved PPARgamma potency and selectivity for 19 when compared to 1.
The thermodynamics of sequestration of toxic copper(ii) metal ion pollutants from aqueous media by l-cysteine methyl ester modified glassy carbon spheres (2006)

L-Cysteine methyl ester modified glassy carbon powder (CysOMe-GC) has been shown to have potential for the removal of toxic heavy metal ions, such as copper(II), cadmium(II) and arsenic(III), from “real” water samples. To develop this material for environmental applications we must develop an understanding of the thermodynamic parameters controlling the uptake of metal ions by the modified carbon powder. Here we characterise the material using X-ray photoelectron spectroscopy (XPS), before investigating the effect of varying the solution pH, the concentration of copper(II) ions and the mass of CysOMe-GC powder added to the solution using square wave voltammetry (SWV). This data allows us to understand the thermodynamics controlling the copper(II) ion uptake and elucidate that the adsorption of copper(II) onto the CysOMe modified surface is controlled by a Freundlich isotherm.
Magnetic levitated drone: "Insector Gadget" (2019)

The Senior Design Project I was assigned was to build a Magnetic Levitated Drone System to be used in Dr. Faraques Research of the dynamics of winged insects. The challenge was to move a small object (the size of a prey or predator) with 6 degrees of Freedom using magnets. Our team proposed to use an array of electromagnetic solenoids to levitate a small neodymium magnet. The system uses a camera and computer vision to track the magnet and uses a PID controller to levitate the object.
A Novel Scheme for Two-Level Stabilization of Semiconductor Mode-Locked Lasers Using Simultaneous Optical Injection and Optical Feedback (2013)

We introduce a novel scheme for the simultaneous reduction of time-bandwidth product (TBP) and RF linewidth of quantum-dash two-section mode-locked lasers using optical injection-locking and filtered optical feedback. The optical injection-locked laser, double-locked with optical feedback showed 2× TBP reduction and RF linewidth reduction by two orders of magnitude. This stabilization technique is implemented in an all-optical arrangement without optical/electrical conversion which is ideal for high-repetition-rate devices and photonic integration.
In <i>Candida albicans</i>, White-Opaque Switchers Are Homozygous for Mating Type (2002)

The relationship between the configuration of the mating type locus (MTL) and white-opaque switching in Candida albicans has been examined. Seven genetically unrelated clinical isolates selected for their capacity to undergo the white-opaque transition all proved to be homozygous at the MTL locus, either MTLa or MTLalpha. In an analysis of the allelism of 220 clinical isolates representing the five major clades of C. albicans, 3.2% were homozygous and 96.8% were heterozygous at the MTL locus. Of the seven identified MTL homozygotes, five underwent the white-opaque transition. Of 20 randomly selected MTL heterozygotes, 18 did not undergo the white-opaque transition. The two that did were found to become MTL homozygous at very high frequency before undergoing white-opaque switching. Our results demonstrate that only MTL homozygotes undergo the white-opaque transition, that MTL heterozygotes that become homozygous at high frequency exist, and that the generation of MTL homozygotes and the white-opaque transition occur in isolates in different genetic clades of C. albicans. Our results demonstrate that mating-competent strains of C. albicans exist naturally in patient populations and suggest that mating may play a role in the genesis of diversity in this pernicious fungal pathogen.
Unusual Geometries in Main Group Chemistry (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Sampled-data observer for 2D Navier-Stokes equation (2019)

We consider sampled-data observer for PDE system governed by the Navier-Stokes equation on the rectangular domain. The system is exponentially stable. We aim to design an observer that exponentially converges to solution with a higher decay rate. We suggested to divide the rectangular domain into N <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> square subdomains, where sensors provide spatially averaged discrete-time state measurements. We derive sufficient conditions ensuring regional exponential stability of the closed-loop system in terms of Linear Matrix Inequalities (LMIs) by using Lyapunov-Krasovskii method. The efficiency of the results is demonstrated by a numerical example.
Preoperative Planning and Imaging (2008)

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