gebhart/patrepeval huggingface dataset:
Retraction: GQ5 Hinders Renal Fibrosis in Obstructive Nephropathy by Selectively Inhibiting TGF-β–Induced Smad3 Phosphorylation (2014)

TGF-β1, via Smad-dependent or Smad-independent signaling, has a central role in the pathogenesis of renal fibrosis. This pathway has been recognized as a potential target for antifibrotic therapy. Here, we identified GQ5, a small molecular phenolic compound isolated from the dried resin of Toxicodendron vernicifluum, as a potent and selective inhibitor of TGF-β1-induced Smad3 phosphorylation. In TGF-β1-stimulated renal tubular epithelial cells and interstitial fibroblast cells, GQ5 inhibited the interaction of Smad3 with TGF-β type I receptor (TβRI) by blocking binding of Smad3 to SARA, suppressed subsequent phosphorylation of Smad3, reduced nuclear translocation of Smad2, Smad3, and Smad4, and downregulated the transcription of major fibrotic genes such as α-smooth muscle actin (α-SMA), collagen I, and fibronectin. Notably, intraperitoneal administration of GQ5 in rats immediately after unilateral ureteral obstruction (UUO) selectively inhibited Smad3 phosphorylation in UUO kidneys, suppressed renal expression of α-SMA, collagen I, and fibronectin, and resulted in impressive renal protection after obstructive injury. Late administration of GQ5 also effectively attenuated fibrotic lesions in obstructive nephropathy. In conclusion, our results suggest that GQ5 hinders renal fibrosis in rats by selective inhibition of TGF-β1-induced Smad3 phosphorylation.
Adjustable Bolted Steel Plate Connection: Measured Behavior of Bolts during Field Installation and Numerical Parametric Investigation (2019)

This paper presents an experimental investigation of bolt behavior in adjustable bolted steel plate connections during field installation and a numerical finite-element (FE) parametric investigation of the impact of (1) bolt diameter; (2) plate thickness; and (3) member flange thickness on the strains induced in the plates and bolts during field installation. The adjustable connection consists of prefabricated cold-bent plates that are further bent during field installation (via bolt tightening) to form moment-resisting joints between steel members. The connection is adjustable because the bolt-tightening field installation process changes the connection angle in situ to accommodate additional angles or manufacturing and erection tolerances. This paper presents the residual bolt surface strains, measured using the full-field photographic technique digital image correlation, providing unprecedented information on the behavior of high-strength bolts. A FE modeling approach for predicting strains in the plates and bolts is developed and validated against measured data. Parametric studies are then performed using the validated FE models with varying bolt diameter, plate thickness, and member flange thickness. Research results are relevant to any misaligned (i.e., nonflush) bolted connections, offering insight into strains from force fitting.
Large-scale Analyses of Disease Biomarkers and Apremilast Pharmacodynamic Effects (2019)

ABSTRACT Finding biomarkers that provide shared link between disease severity, drug-induced pharmacodynamic effects and response status in human trials can provide number of values for patient benefits: elucidating current therapeutic mechanism-of-action, and, back-translating to fast-track development of next-generation therapeutics. Both opportunities are predicated on proactive generation of human molecular profiles that capture longitudinal trajectories before and after pharmacological intervention. Here, we present the largest plasma proteomic biomarker dataset available to-date and the corresponding analyses from placebo-controlled Phase III clinical trials of the phosphodiesterase type 4 inhibitor apremilast in psoriasis (PSOR), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) from 526 subjects overall. Using approximately 150 plasma analytes tracked across three time points, we identified IL-17A and KLK-7 as biomarkers for disease severity and apremilast pharmacodynamic effect in psoriasis patients. Combined decline rate of KLK-7, PEDF, MDC and ANGPTL4 by Week 16 represented biomarkers for the responder subgroup, shedding insights into therapeutic mechanisms. In ankylosing spondylitis patients, IL-6 and LRG-1 were identified as biomarkers with concordance to disease severity. Apremilast-induced LRG-1 increase was consistent with the overall lack of efficacy in ankylosing spondylitis. Taken together, these findings expanded the mechanistic knowledge base of apremilast and provided translational foundations to accelerate future efforts including compound differentiation, combination, and repurposing.
SWISH (2019)

Mixed-reality haptic devices introduce a gateway to otherwise intangible virtual content, creating a life-like immersive experience. Congruent haptic sensation requires faithful integration of visual stimuli and perceived tactile sensation. Unfortunately, current commercial mixed-reality systems are unable to reproduce the physical sensation of fluid vessels, due to the shifting nature of fluid motion. To this end, we introduce SWISH, a novel type of ungrounded mixed-reality system, capable of affording the users a realistic haptic sensation of fluid behavior. We also present solutions to prominent challenges of rendering haptic fluid behavior, especially in coordinate translation and virtual adaptation to physical limitation. Our virtual-to-physical coupling uses Nvidia Flex's Unreal Engine integration, wirelessly controlling a motorized mechanical actuation system housed in a plastic "vessel''. In this paper we discuss the current state of SWISH and present results from our preliminary user study, followed by a description of our future planned phases.
A new conformational search technique and its applications (2005)

The computational identification of the low energy structures of a peptide from its sequence alone has been a problem of major interest for many years. It is not an easy task even for small peptides, due to the mult iple-minima problem and combinatorial explosion. A number of conformational search algorithms have been developed in the past for this purpose. We have developed an algorithm that addresses this problem. In statistical experimental design, mutually orthog onal Latin squares (MOLS) are used to systematically sample the space of the variables. This allows the exper imenter to conduct the experiment with a relatively small number of runs, instead of examining all possible combin ations of values of the variables. We consi dered whether the problem of searching for minimum energy molecular structure on the potential energy surface could also be similarly solved by MOLS sampling. This has led to the development of a conformational search algorithm. In this article, we briefly review the work ca rried out in our laboratory using the MOLS search technique over the last decade.
Development of Cochlear-wall Implants for Electrical Stimulation of the Auditory Nerve (1989)

The aim of these experiments was to investigate the use of titanium implants for anchorage of stimulating electrodes or other clinical or experimental devices in the bony wall of the cochlea. Twenty-six cylindrical titanium fixtures, 0.6 mm in diameter, were inserted into holes drilled in the otic capsule in 8 ears in 5 nonhuman primates and then examined for stability after periods of 2 months to 2 years. Following sacrifice, the bone-metal interfaces were examined microscopically. Fourteen of the implants were firmly fixed in the bone, 6 were loosely fixed and 6 came out. Poor fixation was associated with infection in the middle ear. In uninfected ears, 90% of the implants were stable. The implants were not osseointegrated in the classic sense, but in stable implants, direct bone contact covering 5 to 60% of the titanium oxide surface of the implant shaft was observed.
Achromatic Metalens over 60 nm Bandwidth in the Visible and Metalens with Reverse Chromatic Dispersion (2017)

In this Letter, we experimentally report an achromatic metalens (AML) operating over a continuous bandwidth in the visible. This is accomplished via dispersion engineering of dielectric phase shifters: titanium dioxide nanopillars tiled on a dielectric spacer layer above a metallic mirror. The AML works in reflection mode with a focal length independent of wavelength from λ = 490 to 550 nm. We also design a metalens with reverse chromatic dispersion, where the focal length increases as the wavelength increases, contrary to conventional diffractive lenses. The ability to engineer the chromatic dispersion of metalenses at will enables a wide variety of applications that were not previously possible. In particular, for the AML design, we envision applications such as imaging under LED illumination, fluorescence, and photoluminescence spectroscopy.
Human Pluripotent Stem Cells (iPSC) Generation, Culture, and Differentiation to Lung Progenitor Cells (2016)

Induced pluripotent stem (iPS) cells are the product of adult somatic cell reprogramming to an embryonic-like state by inducing a "forced" expression of specific genes. They are similar to natural pluripotent stem cells, such as embryonic stem (ES) cells, in many aspects, such as the expression of certain stem cell genes and potency and differentiability. Human iPS cells are invaluable resource for basic research, cell therapy, drug discovery, and human organ tissue engineering. iPS cells can be derived from the patient to be treated and thus are genetically identical cells that may avoid immune rejection. The following protocols offer a general guideline for the induction of iPSCs from fibroblasts, and for culture and expansion to produce lung precursor cells.
Novel products from transgenic oil palm. (2003)

Abstract Oil palm ( Elaeis ) is an important economic crop in Malaysia and contributes significantly to the country's economy. Shortage of manpower, arable land and a fluctuating commodity price have forced the industry to widen its scope from being solely dependent on the edible oil market into more diverse applications and higher-return products. Genetic engineering, with all its advantages over conventional breeding, has been identified as a tool for synthesizing high-value-added products in transgenic oil palm. Genetic engineering requires reliable transformation and regeneration systems. Successful production of transgenic oil palm was achieved six years ago. The transgenic plants have started flowering and are still expressing the transgenes. Significant achievements in biochemical studies and isolation of useful oil palm genes and promoters have been reported. A wide range of transformation vectors are being constructed using the genes and promoters from oil palm and are being transformed into oil palm tissue cultures. The latest achievements in the production of transgenic oil palm carrying useful genes are reviewed.
Pulse-compression optical time domain reflectometer (2014)

This paper introduces a novel pulse-compression optical time domain reflectometer (OTDR) by utilizing linear frequency modulation (LFM) pulse-compression technology. The working principle of the pulse-compression OTDR is demonstrated. The spatial resolution is determined by the sweeping range of the pulsed LFM instead of the pulse width, which solves the dilemma of spatial resolution and measurement range in the conventional OTDR. A preliminary experiment of the pulse-compression OTDR is performed, providing 55 cm spatial resolution and 5.4 km measurement range under 2 μs pulse, 221 MHz LFM sweeping range, and 100 kHz linewidth laser diode. It is expectable to achieve a spatial resolution of less than 1 cm and dozens-kilometer measurement range by tens of GHz LFM sweeping ranges via microwave photonics.
Solid polymeric electrolytes based on crosslinked MEEP-type materials (1993)

Poly[di(methoxyethoxyethoxy)phosphazene] (MEEP) is one of the most promising solid polymeric electrolyte matrices for possible uses in rechargeable lithium batteries. Its attributes can be traced to the high skeletal and side group flexibility and to its ability to coordinate to lithium ions and favor ion-pair separation. Radiation cross-linking using ultraviolet light provides dimensional stability without impairing the ionic conductivity.
Programmable Soft Lithography: Solvent-Assisted Nanoscale Embossing (2010)

This paper reports an all-moldable nanofabrication platform that can generate, from a single master, large-area nanoscale patterns with programmable densities, fill factors, and lattice symmetries. Solvent-assisted nanoscale embossing (SANE) could increase the spacing of patterns up to 100% as well as decrease them down to 50% in a single step by stretching or heating a polymer substrate. Also, SANE could reduce critical feature sizes as small as 45% compared to the master by controlled swelling of patterned molds with different solvents. These capabilities were applied to generate plasmonic nanoparticle arrays with continuously variable separations and hence different optical properties on the same substrate.
Distributed dc bus EV charging station using a single dc-link h-bridge multilevel converter (2014)

This paper proposes a novel architecture for Plug-in Electric Vehicles (PEVs) dc charging stations, through the use of a single dc-link 3-level h-bridge (HB) converter as the grid interface. This feature is achieved by the use of an open-ended secondary windings transformer at the grid side. The proposed solution enables fast charging for PEVs concentrating several charging units into a single grid-tied converter. The selected topology provides a three-level waveform without any balancing requirements, enabling a stable dc-bus. Finally, because of the simple nature of the converter, it can be implemented with off-the-shelf components, enabling a low cost alternative for the grid connection of Level III fast chargers.
Microshell-tipped optical fibers as sensors of high-pressure pulses in adverse environments (1984)

We have developed and used an optical-fiber sensor for detecting the arrival of strong pressure pulses. The sensor consists of an optical fiber, tipped with a gas-filled microballoon. They have been used successfully in adverse environments including explosives, ballistics and electromagnetic pulses (EMP). The sensor produces a bright optical pulse caused by the rapid shock-heating of a gas, typically argon or xenon, which is confined in the spherical glass or plastic microballoon. The light pulse is transmitted via the optical fiber to a photo detector, usually a streak camera or photomultiplier tube. The microballoon optical sensor (called an optical pin by analogy to standard electrical pins), was originally developed for diagnosing an explosive, pulsed-power generator. Optical pins are required due to the EMP. The optical pins are economical arrival-time indicators because many channels can be recorded by one streak camera. The generator tests and related experiments, involving projectile velocities and detonation velocities of several kilometers per/sec have demonstrated the usefulness of the sensors in explosives and ballistics applications. We have also measured the sensitivity of the optical pins to slowly-moving projectiles and found that a 200 m/sec projectile impacting the microballoon sensor produces a flash having a risetime less than 100 ns and a pulse duration (FWHM) of less than 300 ns. The technical and cost advantages of this optical pin make it potentially useful for many electromagnetic, explosive, and ballistics applications.
Regulation of a lightweight high efficiency capacitor diode voltage multiplier DC-DC converter (1976)

A method for the regulation of a capacitor diode voltage multiplier dc-dc converter has been developed which has only minor penalties in weight and efficiency. An auxiliary inductor is used, which only handles a fraction of the total power, to control the output voltage through a pulse width modulation method in a buck boost circuit.
Treating Refractory Mental Illness With Closed-Loop Brain Stimulation: Progress Towards a Patient-Specific Transdiagnostic Approach (2022)

Mental disorders are a leading cause of disability, morbidity, and mortality among civilian and military populations. Most available treatments have limited efficacy, particularly in disorders where symptoms vary over relatively short time scales. Targeted modulation of neural circuits, particularly through open-loop deep brain stimulation (DBS), showed initial promise but has failed in blinded clinical trials. We propose a new approach, based on targeting neural circuits linked to functional domains that cut across diagnoses. Through that framework, which includes measurement of patients using six psychophysical tasks, we seek to develop a closed-loop DBS system that corrects dysfunctional activity in brain circuits underlying those domains. We present convergent preliminary evidence from functional neuroimaging, invasive human electrophysiology, and human brain stimulation experiments suggesting that this approach is feasible. Using the Emotional Conflict Resolution (ECR) task as an example, we show that emotion-related networks can be identified and modulated in individual patients. Invasive and non-invasive methodologies both identify a network between prefrontal cortex, cingulate cortex, insula, and amygdala. Further, stimulation in cingulate and amygdala changes patients' performance in ways that are linked to the task's emotional content. We present preliminary statistical models that predict this change and allow us to track it at a single-trial level. As these diagnostic and modeling strategies are refined and embodied in an implantable device, they offer the prospect of a new approach to psychiatric treatment and its accompanying neuroscience.
Note: Design and construction of a multi-scale, high-resolution, tube-generated X-Ray computed-tomography system for three-dimensional (3D) imaging (2014)

The design and construction of a high resolution modular x-ray computed tomography (XCT) system is described. The approach for meeting a specified set of performance goals tailored toward experimental versatility is highlighted. The instrument is unique in its detector and x-ray source configuration, both of which enable elevated optimization of spatial and temporal resolution. The process for component selection is provided. The selected components are specified, the custom component design discussed, and the integration of both into a fully functional XCT instrument is outlined. The novelty of this design is a new lab-scale detector and imaging optimization through x-ray source and detector modularity.
Fast Reconfiguring Deep Packet Filter for 1+ Gigabit Network (2005)

Due to increasing number of network worms and virus, many computer network users are vulnerable to attacks. Unless network security systems use more advanced methods of content filtering such as deep packet inspection, the problem get worse. However, searching for patterns at multiple offsets in entire content of network packet requires more processing power than most general purpose processor can provide. Thus, researchers have developed high performance parallel deep packet filters for reconfigurable devices. Although some reconfigurable systems can be generated automatically from pattern database, obtaining high performance result from each subsequent reconfiguration can be a time consuming process. We present a novel architecture for programmable parallel pattern matching coprocessor. By combining a scalable coprocessor with the compact reconfigurable filter, we produce a hybrid system that is able to update the rules immediate during the time the new filter is being compiled. We mapped our hybrid filter for the latest Snort rule set on January 13, 2005, containing 2,044 unique patterns byte make up 32,384 bytes, onto a single Xilinx Virtex 4LX-XC4VLX15 FPGA with a filtering rate of 2 Gbps.
Experimental Comparison of Three Floating Wind Turbine Concepts (2012)

Beyond many of the Earth’s coasts exist a vast deepwater wind resource that can be tapped to provide substantial amounts of clean, renewable energy. However, much of this resource resides in waters deeper than 60 m where current fixed bottom wind turbine technology is no longer economically viable. As a result, many are looking to floating wind turbines as a means of harnessing this deepwater offshore wind resource. The preferred floating platform technology for this application, however, is currently up for debate. To begin the process of assessing the relative advantages of various platform concepts for floating wind turbines, 1/50th scale model tests in a wind/wave basin were performed at MARIN (Maritime Research Institute Netherlands) of three floating wind turbine concepts. The Froude scaled tests simulated the behavior of the 126 m rotor diameter NREL (National Renewable Energy Lab) 5 MW, horizontal axis Reference Wind Turbine attached via a flexible tower in turn to three distinct platforms, these being a tension leg-platform, a spar-buoy and a semi-submersible. A large number of tests were performed ranging from simple free-decay tests to complex operating conditions with irregular sea states and dynamic winds. The high-quality wind environments, unique to these tests, were realized in the offshore basin via a novel wind machine which exhibited low swirl and turbulence intensity in the flow field. Recorded data from the floating wind turbine models include rotor torque and position, tower top and base forces and moments, mooring line tensions, six-axis platform motions and accelerations at key locations on the nacelle, tower, and platform. A comprehensive overview of the test program, including basic system identification results, is covered in an associated paper in this conference. In this paper, the results of a comprehensive data analysis are presented which illuminate the unique coupled system behavior of the three floating wind turbines subjected to combined wind and wave environments. The relative performance of each of the three systems is discussed with an emphasis placed on global motions, flexible tower dynamics and mooring system response. The results demonstrate the unique advantages and disadvantages of each floating wind turbine platform.
Differential Susceptibility of HIV-1 Reverse Transcriptase to Inhibition by RNA Aptamers in Enzymatic Reactions Monitoring Specific Steps during Genome Replication (2006)

Nucleic acid aptamers to HIV-1 reverse transcriptase (RT) are potent inhibitors of DNA polymerase function in vitro, and they have been shown to inhibit viral replication when expressed in cultured T-lymphoid lines. We monitored RT inhibition by five RNA pseudoknot RNA aptamers in a series of biochemical assays designed to mimic discrete steps of viral reverse transcription. Our results demonstrate potent aptamer inhibition (IC50 values in the low nanomolar range) of all RT functions assayed, including RNA- and DNA-primed DNA polymerization, strand displacement synthesis, and polymerase-independent RNase H activity. Additionally, we observe differences in the time dependence of aptamer inhibition. Polymerase-independent RNase H activity is the most resistant to long term aptamer suppression, and RNA-dependent DNA polymerization is the most susceptible. Finally, when DNA polymerization was monitored in the presence of an RNA aptamer in combination with each of four different small molecule inhibitors, significant synergy was observed between the aptamer and the two nucleoside analog RT inhibitors (azidothymidine triphosphate or ddCTP), whereas two non-nucleoside analog RT inhibitors showed either weak synergy (efavirenz) or antagonism (nevirapine). Together, these results support a model wherein aptamers suppress viral replication by cumulative inhibition of RT at every stage of genome replication.