gebhart/patrepeval huggingface dataset:
Dystrophin Expressing Chimeric (DEC) Human Cells Provide a Potential Therapy for Duchenne Muscular Dystrophy (2018)

Duchenne Muscular Dystrophy (DMD) is a progressive and lethal disease caused by mutations of the dystrophin gene. Currently no cure exists. Stem cell therapies targeting DMD are challenged by limited engraftment and rejection despite the use of immunosuppression. There is an urgent need to introduce new stem cell-based therapies that exhibit low allogenic profiles and improved cell engraftment. In this proof-of-concept study, we develop and test a new human stem cell-based approach to increase engraftment, limit rejection, and restore dystrophin expression in the mdx/scid mouse model of DMD. We introduce two Dystrophin Expressing Chimeric (DEC) cell lines created by ex vivo fusion of human myoblasts (MB) derived from two normal donors (MB<sup>N1</sup>/MB<sup>N2</sup>), and normal and DMD donors (MB<sup>N</sup>/MB<sup>DMD</sup>). The efficacy of fusion was confirmed by flow cytometry and confocal microscopy based on donor cell fluorescent labeling (PKH26/PKH67). In vitro, DEC displayed phenotype and genotype of donor parent cells, expressed dystrophin, and maintained proliferation and myogenic differentiation. In vivo, local delivery of both DEC lines (0.5 × 10<sup>6</sup>) restored dystrophin expression (17.27%±8.05-MB<sup>N1</sup>/MB<sup>N2</sup> and 23.79%±3.82-MB<sup>N</sup>/MB<sup>DMD</sup>) which correlated with significant improvement of muscle force, contraction and tolerance to fatigue at 90 days after DEC transplant to the gastrocnemius muscles (GM) of dystrophin-deficient mdx/scid mice. This study establishes DEC as a potential therapy for DMD and other types of muscular dystrophies.
Formation of Part Families for Shared Setups Generation in Sheet Metal Bending (1998)

Abstract Sheet metal bending press-brakes can be setup to produce more than one type of parts without requiring a setup change. To exploit this flexibility, we need setup planning techniques to generate press-brake setups that can be shared among many different parts. In this paper, we describe an algorithm which partitions a given set of parts into setup compatible part families which can be produced on the same setup. Our algorithm is based on a two step approach. The first step is to identify setup constraints for each individual part. The second step is to form setup-compatible part families based on the compatibility of setup constraints. We expect that by producing many different types of parts on the same setup, we can significantly reduce the required number of setups and enable cost effective small batch manufacturing.
A specific antidote for dabigatran: functional and structural characterization (2013)

Dabigatran etexilate is a direct thrombin inhibitor and used widely as an anticoagulant for the prevention of stroke in patients with atrial fibrillation. However, anticoagulation therapy can be associated with an increased risk of bleeding. Here, we present data on the identification, humanization, and in vitro pharmacology of an antidote for dabigatran (aDabi-Fab). The X-ray crystal structure of dabigatran in complex with the antidote reveals many structural similarities of dabigatran recognition compared with thrombin. By a tighter network of interactions, the antidote achieves an affinity for dabigatran that is ~350 times stronger than its affinity for thrombin. Despite the structural similarities in the mode of dabigatran binding, the antidote does not bind known thrombin substrates and has no activity in coagulation tests or platelet aggregation. In addition we demonstrate that the antidote rapidly reversed the anticoagulant activity of dabigatran in vivo in a rat model of anticoagulation. This is the first report of a specific antidote for a next-generation anticoagulant that may become a valuable tool in patients who require emergency procedures.
Tailoring of High‐Order Multiple Emulsions by the Liquid–Liquid Phase Separation of Ternary Mixtures (2014)

Multiple emulsions with an "onion" topology are useful vehicles for drug delivery, biochemical assays, and templating materials. They can be assembled by ternary liquid phase separation by microfluidics, but the control over their design is limited because the mechanism for their creation is unknown. Herein we show that phase separation occurs through self-similar cycles of mass transfer, spinodal decomposition or nucleation, and coalescence into multiple layers. Mapping out the phase diagram shows a linear relationship between the diameters of concentric layers, the slope of which depends on the initial ternary composition and the molecular weight of the surfactant. These general rules quantitatively predict the number of droplet layers (multiplicity), which we used to devise self-assembly routes for polymer capsules and liposomes. Moreover, we extended the technique to the assembly of lipid-stabilized droplets with ordered internal structures.
Lowering the Error Floor of Turbo Codes With CRC Verification (2016)

Decoding performance of turbo codes can flatten at moderately high signal-to-noise ratio. This letter proposes a low complexity method for lowering this error floor. This method rests on the observation of the extrinsic information during the iterative decoding process. A set of q most unreliable bits are identified based on their associated extrinsic information. A total of 2 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">q</sup> test patterns are then built by inverting the most unreliable bits. The decoded codeword is identified thanks to a cyclic redundancy check detector. This method keeps the turbo coding scheme unchanged as long as an error detection code is serially concatenated with the turbo code. Simulations were performed on a rate-1/3 Long-Term Evolution turbo code and show an improvement of at least one decade in terms of frame error rate in the error floor region. This low complexity method paves the way for further improvements in lowering the error floor of turbo codes.
Beam tilt and angular dispersion in broad-bandwidth, nanosecond optical parametric oscillators (1999)

We show that the signal and idler beams generated by certain types of unseeded, nanosecond optical parametric oscillators are tilted and angularly dispersed and have anomalously large bandwidths. This effect is demonstrated in both laboratory measurements and a numerical model. We show how the optical cavity design influences the tilts and how these tilts can be eliminated or minimized. We also determine the conditions necessary for injection seeding of these parametric oscillators.
Action Segmentation with Mixed Temporal Domain Adaptation (2021)

The main progress for action segmentation comes from densely-annotated data for fully-supervised learning. Since manual annotation for frame-level actions is time-consuming and challenging, we propose to exploit auxiliary unlabeled videos, which are much easier to obtain, by shaping this problem as a domain adaptation (DA) problem. Although various DA techniques have been proposed in recent years, most of them have been developed only for the spatial direction. Therefore, we propose Mixed Temporal Domain Adaptation (MTDA) to jointly align frame- and video-level embedded feature spaces across domains, and further integrate with the domain attention mechanism to focus on aligning the frame-level features with higher domain discrepancy, leading to more effective domain adaptation. Finally, we evaluate our proposed methods on three challenging datasets (GTEA, 50Salads, and Breakfast), and validate that MTDA outperforms the current state-of-the-art methods on all three datasets by large margins (e.g. 6.4% gain on F1@50 and 6.8% gain on the edit score for GTEA).
Non-contact laser ultrasound concept for biomedical imaging (2017)

The potential of a fully noncontact, standoff, laserultrasound system that acquires ultrasonic images within biological tissue is examined. A pulsed laser converts optical energy into ultrasound via photoacoustic mechanisms, while laser Doppler vibrometry measures emerging ultrasonic waves at the tissue surface. Differing from photoacoustic tomography (PAT), which maps spatial variations in tissue-optical absorptivity in the acoustic near field, the laser ultrasound (LUS) approach developed here, is driven by shallow, non-varying optical absorptivity that creates a laterally consistent acoustic source enabling ultrasound propagation well into the far field. LUS acoustic wave generation is explored in tissue and bone including longitudinal, shear, and Rayleigh wave components. Using information from LUS wave types can yield 1) tissue and bone anatomical images and 2) mechanical property distributions that apply to the emerging field of medical elastography. Imaging capabilities using a demonstration LUS system are also presented for complex bio-tissues. Ultrasonic images compare well with ground truth geometries, orientation, and depth of staged samples. 2D cross-sectional echo reflection images are generated for a phantom limb containing muscle and bone materials and use data inversion techniques to yield the elastic moduli distributions in the specimen.
Solution mixing and the emission of light in flow-cells for chemiluminescence detection (2010)

Constructing flow-through reactors for chemiluminescence detection by machining channels into polymer disks has enabled the exploration of new configurations and materials that can improve signal intensity beyond that attainable with the traditional coiled-tubing design. Several approaches to merge reactant solutions were examined: an intersection, chamber or deeper well in the centre of a serpentine configuration flow-cell (directly in front of a photomultiplier tube), or a confluence point outside the detection zone. For several analytically useful, rapid chemiluminescence reactions, the single-inlet flow-cell with external Y-piece was most suitable, but for others (such as KMnO(4)/Mn(II) with morphine, and [Ir(f-ppy)(2)BPS](-) with fluoroquinolones) the dual-inlet configuration provided greater signals. The introduction of central mixing zones with larger widths than the channel reduced the chemiluminescence response. The reversing turns of a serpentine channel promote efficient mixing and greater chemiluminescence intensities than a spiral channel, but increasing the sharpness of the turns created areas of poor solution flow and decreased the chemiluminescence response. Teflon disks impregnated with glass microspheres increased the chemiluminescence signals by 13%-17%, due to the greater reflection of stray light towards the photodetector.
Quantitative analysis of reconstructed 3-D coronary arterial tree and intracoronary devices (2002)

Traditional quantitative coronary angiography is performed on two-dimensional (2-D) projection views. These views are chosen by the angiographer to minimize vessel overlap and foreshortening. With 2-D projection views that are acquired in this nonstandardized fashion, however, there is no way to know or estimate how much error occurs in the QCA process. Furthermore, coronary arteries possess a curvilinear shape and undergo a cyclical deformation due to their attachment to the myocardium. Therefore, it is necessary to obtain three-dimensional (3-D) information to best describe and quantify the dynamic curvilinear nature of the human coronary artery. Using a patient-specific 3-D coronary reconstruction algorithm and routine angiographic images, a new technique is proposed to describe: 1) the curvilinear nature of 3-D coronary arteries and intracoronary devices; 2) the magnitude of the arterial deformation caused by intracoronary devices and due to heart motion; and 3) optimal view(s) with respect to the desired "pathway" for delivering intracoronary devices.
Design and synthesis of potent macrocyclic HIV-1 protease inhibitors involving P1–P2 ligands (2014)

A series of potent macrocyclic HIV-1 protease inhibitors have been designed and synthesized. The compounds incorporated 16- to 19-membered macrocyclic rings between a nelfinavir-like P2 ligand and a tyrosine side chain containing a hydroxyethylamine sulfonamide isostere. All cyclic inhibitors are more potent than their corresponding acyclic counterparts. Saturated derivatives showed slight reduction of potency compared to the respective unsaturated derivatives. Compound containing a 16-membered ring as the P1-P2 ligand showed the most potent enzyme inhibitory and antiviral activity.
Space-time-state block coded mimo communication systems using reconfigurable antennas (2009)

Reconfigurable antennas offer a promising solution to the problem of space limitation in high-performance wireless communication over handset devices. In this paper, we propose a novel transmission scheme capable of extracting the maximum diversity gains of a Multiple-Input Multiple-Output (MIMO) communication system employing reconfigurable antennas at the transmitter, the receiver or at both ends of the wireless link, without the need for feedback. For a MIMO communication system using reconfigurable antennas at the transmitter, we propose a state-switching scheme in combination with an appropriate three-dimensional block code in order to extract the maximum possible level of diversity. When reconfigurable antennas are placed at the receiver end, we propose a state-selection scheme and prove that the proposed scheme is capable of achieving maximum diversity gains. Moreover, the state-selection method is able to obtain selection gain in addition to diversity gain. As shown, both state-switching and state-selection schemes can be combined together when reconfigurable antennas are used at both ends of the wireless link. Furthermore, we discuss and quantify the effects of switching delay on the performance of both state-switching and state-selection schemes. Finally, we provide simulation results to validate the performance of the proposed schemes. To demonstrate the gains of our schemes in realistic propagation conditions, we also conduct simulations using an actual reconfigurable antenna known as the PIXEL antenna.
γ-Secretase Inhibitors Prevent Overgrowth of Transplanted Neural Progenitors Derived from Human-Induced Pluripotent Stem Cells (2012)

Although transplanted pluripotent stem cell-derived neurons can contribute to functional recovery in animal models of Parkinson's disease, the risk of tumor formation hinders clinical applications of this approach. Removing undifferentiated cells from the donor population is critical to reduce tumorigenesis. Moreover, immature neural progenitors in transplants can proliferate unpredictably, resulting in neural overgrowth and long-term risks of compressing the surrounding host tissue. Because Notch signaling plays a role in maintaining the multipotency and proliferative capacity of neural progenitors, we used γ-secretase inhibitors (GSIs) to dampen Notch signaling in human-induced pluripotent stem cell-derived neural progenitors before transplantation and examined the effects on the growth of proliferative grafts. We observed a marked reduction in the percentage of dividing cells and increased neuronal maturation in GSI-treated samples in vitro. Next, grafts were transplanted into the striata of nonobese diabetic/severe combined immune deficiency mice. Histological analyses performed 8 weeks after the operation showed that grafts pretreated with GSIs--N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester or compound E--were significantly smaller than control samples. Immunohistologic analyses revealed that briefly treating the donor population with GSIs not only reduced the graft volume, but also altered the composition of the graft; control grafts showed neural overgrowth with numerous PAX6+ and Ki67+ neural rosettes, whereas GSI-treated samples developed into mature neuronal grafts containing primarily Tubβ3+ cells. These results suggest that pretreating potentially proliferative progenitors with GSIs may improve the safety of cell replacement therapies using pluripotent stem cells.
Design and construction of a rapid thermal processing system for <i>in</i> <i>situ</i> optical measurements (1996)

A rapid thermal processing system is described incorporating features that enable in situ optical measurements. In particular, a system incorporating an in situ spectroscopic ellipsometer is described highlighting some of the unusual features necessary for ellipsometry measurements. These features include independent optical, vacuum, and heating modules, optical and heating window design, reflector design, and sample manipulation to enable proper positioning for measurement. Although specifically designed with ellipsometry in mind, many of the same principles used in the design of this system will apply to systems for other optical measurements.
A baseline object detection algorithm using background anomalies for electro-optic identification sensors (2005)

Electro-optic identification sensors provide photographic quantity that can be used to identify mine-like contacts provided by long-range sensors, such as sonar systems. Computer aided identification and automatic target recognition algorithms have been funded by the Office of Naval Research (322-OP) to help operators in the identification process. Under this funding, a new background anomaly approach was introduced (Nevis et al., 2002) for object detection using a least square error (LSE) background best fit searching for anomalies of certain specified size and shape (and SNR) that stick out from the local background. This initial approach has been refined into a baseline algorithm. An overview of this baseline algorithm is presented in this paper, with an emphasis on modifications from the initial approach.
A New Computational Technique for the Generation of Optimised Aircraft Trajectories (2017)

Abstract A new computational technique based on Pseudospectral Discretisation (PSD) and adaptive bisection ε -constraint methods is proposed to solve multi-objective aircraft trajectory optimisation problems formulated as nonlinear optimal control problems. This technique is applicable to a variety of next-generation avionics and Air Traffic Management (ATM) Decision Support Systems (DSS) for strategic and tactical replanning operations. These include the future Flight Management Systems (FMS) and the 4-Dimensional Trajectory (4DT) planning and intent negotiation/validation tools envisaged by SESAR and NextGen for a global implementation. In particular, after describing the PSD method, the adaptive bisection ε -constraint method is presented to allow an efficient solution of problems in which two or multiple performance indices are to be minimized simultaneously. Initial simulation case studies were performed adopting suitable aircraft dynamics models and addressing a classical vertical trajectory optimisation problem with two objectives simultaneously. Subsequently, a more advanced 4DT simulation case study is presented with a focus on representative ATM optimisation objectives in the Terminal Manoeuvring Area (TMA). The simulation results are analysed in-depth and corroborated by flight performance analysis, supporting the validity of the proposed computational techniques.
Size-selective fractionation of nanoparticles at an application scale using CO<sub>2</sub>gas-expanded liquids (2009)

Size-based fractionation of nanoparticles remains a non-trivial task for the preparation of well-defined nanomaterials for certain applications and fundamental studies. Typical fractionation techniques prove to be inefficient for large nanoparticle quantities due to several factors including the expense of equipment, throughput constraints, and the amount of organic solvent waste produced. Through the use of the pressure-tunable physico-chemical properties of CO2-expanded liquids, a rapid, precise, and environmentally sustainable size-selective fractionation of ligand-stabilized nanoparticles is possible through simple variations in applied CO2 pressure. An apparatus capable of fractionating large quantities of nanoparticles into distinct fractions with the ability to control mean diameters and size distributions has been developed. This apparatus consists of three vertically mounted pressure vessels connected in series with needle valves. This process, at current design scales, operated at room temperature, and CO2 pressures between 0 and 50 bar, results in a batch size-selective fractionation of a concentrated nanoparticle dispersion. This paper presents this new apparatus and the separation results of various single pass fractionations as well as recursive fractionations.
3-D Cauchy-type integrals for terrain correction of gravity and gravity gradiometry data (2013)

Fundamental to complex analysis is the Cauchy integral theorem, and the derivation of Cauchy-type integrals. For over 40 yr, Cauchy-type integrals have been used to describe analytical continuation, establish the location of singular points, and study non-single-valued solutions of inverse problems in 2-D potential field theory. In this paper, we revive this interesting and fundamental area of potential field theory to introduce Cauchy-type integrals for 3-D potential fields. In particular, we show how one can evaluate the gravity and gravity gradiometry responses of 3-D bodies as surface integrals over arbitrary volumes that may contain spatially variable densities. This method of 3-D spatial-domain potential field modelling has never been realized before, and we show how it is particularly suited to the terrain correction of airborne gravity and gravity gradiometry data. The surface integrals are evaluated numerically on a topographically conforming grid with a resolution equal to the digital elevation model. Thus, our method directly avoids issues related to prismatic discretization of the digital elevation model and their associated volume integration which may result in inappropriate discretization of the earth model, particularly for regions of rugged topography. We demonstrate our method with a model study for airborne gravity gradiometry data simulated for a next-generation 1 Eö/<f>$\\sqrt{\\text{Hz}}$</f> system over the Kauring test site in Western Australia.
A Potential New Therapeutic Approach for Friedreich Ataxia: Induction of Frataxin Expression With TALE Proteins (2013)

TALEs targeting a promoter sequence and fused with a transcription activation domain (TAD) may be used to specifically induce the expression of a gene as a potential treatment for haploinsufficiency. This potential therapeutic approach was applied to increase the expression of frataxin in fibroblasts of Friedreich ataxia (FRDA) patients. FRDA fibroblast cells were nucleofected with a pCR3.1 expression vector coding for TALEFrat#8 fused with VP64. A twofold increase of the frataxin mRNA (detected by quantitative reverse transcription-PCR (qRT-PCR)) associated with a similar increase of the mature form of the frataxin protein was observed. The frataxin mRNA and protein were also increased by this TALE in the fibroblasts of the YG8R mouse model. The addition of 5-aza-2'-deoxycytidine (5-Aza-dC) or of valproic acid (VPA) to the TALE treatment did not produce significant improvement. Other TADs (i.e., p65, TFAP2α, SRF, SP1, and MyoD) fused with the TALEFrat#8 gene did not produce a significant increase in the frataxin protein. Thus the TALEFrat#8-VP64 recombinant protein targeting the frataxin promoter could eventually be used to increase the frataxin expression and alleviate the FRDA symptoms.Molecular Therapy-Nucleic Acids (2013) 2, e119; doi:10.1038/mtna.2013.41; published online 3 September 2013.