gebhart/patrepeval huggingface dataset:
617. Identification of Novel AAV Capsid Variants with Enhanced Tropism for the Canine Outer Retina Following Intravitreal Delivery (2016)

The delivery of AAV vectors across physical barriers to target the outer retina is key to the success of retinal gene therapies. Subretinal injection of AAV vectors is the most common approach to deliver genes to photoreceptors and RPE; however, this route of administration presents surgical challenges and potential complications, as well as mediates transfer to only a limited region of the retinal surface. Intravitreal administration may represent a safer way of targeting larger areas of the outer retina; physical barriers such as the internal limiting membrane significantly limit efficiency of natural AAVs through this route. In a prior murine proof of concept study, we showed that directed evolution is promising method for engineering new AAV capsid variants with enhanced permissivity for the outer retina. Here, we show results from a screen performed in the canine retina, a large animal model with eye structure and size similar to the human eye. A library of >107 distinct capsid variant AAV vectors was injected intravitreally into the eye of a wildtype dog. A subset of the AAV vectors injected was recovered from samples of outer retina by PCR amplification. Isolated variants were then pooled and re-injected in additional wildtype canine eyes, and following 5 total rounds of selection the pool had converged to a relatively small number of variants. High throughput sequencing was used to characterize the convergence of variants over all rounds of selection. The final candidate variants were then evaluated by packaging a GFP reporter controlled by a ubiquitous CAG promoter. Retinal distribution and cellular tropism of the variants was examined by cSLO (AF mode) imaging, histology and immunocytochemistry. Nineteen variants were identified as candidate vectors for targeting the canine outer retina. Intravitreal injection of a mixture of equal amounts of these variants carrying GFP fused to a barcode resulted in efficient targeting of all retinal layers including photoreceptors and RPE in 6 eyes of 3 wildtype dogs. Thus, directed evolution performed in a large animal model, with an eye structure similar to that of humans, resulted in new AAV capsid variants with improved abilities to bypass significant structural barriers and efficiently transduce the outer retina. High throughput sequencing allowed for identification of promising variants and monitoring of convergence. These vectors show promise for gene therapy delivery via the intravitreal route of administration, potentially providing a safer approach for targeting a larger area of outer retina than currently achieved by the more traumatic and focal subretinal injection method.
Non-Invasive Characterization Of A Flowing Multi-Phase Fluid Using Ultrasonic Interferometry (2005)

An apparatus for noninvasively monitoring the flow and/or the composition of a flowing liquid using ultrasound is described. The position of the resonance peaks for a fluid excited by a swept-frequency ultrasonic signal have been found to change frequency both in response to a change in composition and in response to a change in the flow velocity thereof. Additionally, the distance between successive resonance peaks does not change as a function of flow, but rather in response to a change in composition. Thus, a measurement of both parameters (resonance position and resonance spacing), once calibrated, permits the simultaneous determination of flow rate and composition using the apparatus and method of the present invention.
<title>X-ray microscopy studies with the Goettingen x-ray microscopes</title> (1993)

Zone plates with improved resolution have been constructed by electron beam lithography. With these zone plates features as small as 30 nm can be imaged without astigmatism. By using the phase shifting property of the zone plate material and by an improved etching technique, groove efficiency values up to 10% have been measured. A new type of foils for the support of the zone plates as well as for the x-ray windows are more stable under synchrotron radiation than the polyimide foils used before and have a higher transmission for x-rays in the `water-window' region. The x-ray microscope installed at BESSY, Berlin, Germany was modified in such a way that the environmental chamber is now placed in air with better access to the specimens under investigation. In addition, a light microscope was incorporated in the x-ray microscope providing a better practicability to adjust object details to the object field of the x-ray microscope, selecting another object or object detail to be investigated, and prefocussing the object for x-ray imaging. With the improved x-ray microscope different wet biological specimens and test structures were investigated, showing features as small as 30 nm. The x-ray microscope using a pulsed plasma x-ray source, installed in Gottingen, Germany was modified in such a way that instead of a zone plate an ellipsoidal mirror is used as the condenser. The pulsed plasma x-ray source was improved too, i.e., the number of pulses needed for an image is reduced.
The Polar High Molecular Weight Fraction of the <i>Agaricus blazei</i> Murill Extract, AndoSan™, Reduces the Activity of the Tumor-Associated Protease, Legumain, in RAW 264.7 Cells (2014)

AndoSan™ is an extract of Agaricus blazei Murill (AbM; 82.4%), Hericium erinaceum (14.7%), and Grifola frondosa (2.9%). The main ingredient of AndoSan, AbM, is rich in different forms of β-glucans. Since these exhibit potent antitumor activity and have immunomodulatory effects, the stimulatory effect of AndoSan on the production of different cytokines, chemokines, and leukocyte growth factors has predominantly been attributed to β-glucans. AndoSan has been claimed to consist of 90% carbohydrate, of which 2.8% is β-glucans, but in this study, we show that the carbohydrate content is only 2% of the dry weight, corresponding to 0.09% β-glucan per mL of AndoSan. Fractionation of AndoSan, followed by carbohydrate analysis and HPLC analysis revealed that most of the glucose was concentrated in the polar high molecular weight fraction of AndoSan (ethanol insoluble water extract [EIWE]-A) and that this extract was able to significantly inhibit the activity of the tumor-associated protease, legumain, in RAW 264.7 cells. Legumain is synthesized as a zymogen and undergoes pH-dependent autoactivation of the proform to reach an enzymatically active form. In this study, we demonstrate that both the polar and nonpolar AndoSan fractions are able to inhibit the autoactivation of prolegumain, and that the polar fractions of AndoSan are the most potent inhibitors of the active form of the enzyme.
Properties and applications of optical thyristors (1994)

The optical thyristor is a promising device for optical information processing. It combines a receiving-, transmitting- and memory function in a single device, with at the same time a considerable optical gain. We show in this paper the dynamics of differential switching, i.e., the switching of a single thyristor in an array of thyristors, and compare it to the switching of a single device. We also review the recent developments which have led to a dramatic increase of the speed and optical sensitivity of optical thyristors. Finally, we show some interesting applications which have been realized with differential switching in arrays of sensitive thyristors (5 ×5, 16 ×16 unto 32 ×64 devices), such as locating the maximum light intensity or integrated intensity of optical input patterns, and transcription of optical information from one thyristor array to another in free space.
Image Enhancement with Polymer Grid Triode Arrays (1995)

An array of polymer grid triodes connected by a common grid functions as a “plastic retina,” providing local contrast gain control for image enhancement. This simple device, made from layers of conducting polymers, functions as an active resistive network that performs center-surround filtering. The polymer grid triode array with common grid is a continuous analog of the discrete approach of Mead, with a variety of fabrication advantages and significant savings in area within the unit cell of each pixel.
A novel vectorcardiogram system (2014)

This paper presents the proof-of-concept investigation for a miniaturized vectorcardiogram [VCG] system for ambulatory on-body applications that continuously monitors the electrical activity of the heart in three dimensions. We investigate the minimum distance between a pair of leads in the X, Y and Z axes such that the signals are distinguishable from the noise. The target dimensions for our VCG are 3×3×2 cm and, based on our preliminary results, it is possible to achieve these dimensions. The next step in our research is to build the miniaturized VCG system that includes processing, learning and communication capabilities.
A global maximum power point tracking method for PV module integrated converters (2012)

This paper proposes a maximum power point tracking (MPPT) method to seek the global maximum power point (MPP) in photovoltaic (PV) modules. The method infers partial shading-and hence the possibility of multiple maxima-by monitoring bypass-diode voltages and initiates a global search routine only if a bypass diode turns on. Under nominal conditions, conventional MPPT is implemented through a perturbation-based approach. This technique provides a significant advantage over existing methods to counter partial shading that periodically scan the entire PV power profile. Experimental results demonstrate the ability of the algorithm to track the global MPP for string and cell-level shading scenarios.
Characterization of a Drosophila protein that binds both epidermal growth factor and insulin-related growth factors. (1987)

The identification of a novel protein from Drosophila melanogaster that binds both mammalian epidermal growth factor (EGF) and insulin has been reported (Thompson, K. L., S. J. Decker, and M. R. Rosner, 1985, Proc. Natl. Acad. Sci. USA., 82:8443-8447). This 100-kD protein (designated dp100) is also recognized by an antiserum against the human EGF receptor. To further characterize the properties of this protein, we have determined the binding spectrum, glycosylation state, and cellular distribution of dp100. Our results indicate that dp100 binds to other insulin-like and EGF-like growth factors with dissociation constants ranging from 10(-6) to 10(-9) M, and these ligands compete with each other for binding to dp100. All other ligands tested, including platelet-derived growth factor, transforming growth factor-beta, nerve growth factor, and glucagon, either did not bind or bound with a Kd greater than 10(-6) M. Unlike the Drosophila insulin receptor, dp100 does not bind to wheat germ agglutinin and is present in a cytoplasmic as well as a membrane-bound form that cannot be differentiated by two-dimensional PAGE. Further, dp100 is the sole transforming growth factor-alpha-binding protein detected by affinity labeling in Drosophila Kc cells. These results indicate that dp100 shares properties in common with, but distinct from, the Drosophila homologues of the insulin and EGF receptors.
A Chloroacetamidine‐Based Inactivator of Protein Arginine Methyltransferase 1: Design, Synthesis, and In Vitro and In Vivo Evaluation (2010)

Protein arginine methyltransferases (PRMTs) catalyze the post-translational methylation of arginine residues. PRMT1 is the predominant mammalian isozyme and is responsible for generating the majority of the asymmetrically dimethylated arginine found in vivo. Herein, we describe the most potent PRMT1 inhibitor, C21, described to date. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Real-time rendering of realistic rain (2006)

We propose a new GPU based technique to render realistic rain in real-time. It consists of two parts: off-line image analysis of rain videos, and real-time particle-based synthesis of rain. Videos of real rain are analyzed to extract the rain mattes; random samples of these rain stroke mattes are then used for online synthesis. We incorporate pre-computed radiance transfer (PRT) in our particle system to take into account the scene radiance. The transfer function of a raindrop can be highly efficiently evaluated with a closed-form solution. Our approach achieves high realism with low computation cost and a small memory footprint. Our technique applies to a variety of scenarios, from synthetic 3D scenes to real videos.
Curcumin Conjugates of Non‐steroidal Anti‐Inflammatory Drugs: Synthesis, Structures, Anti‐proliferative Assays, Computational Docking, and Inflammatory Response (2020)

In an effort to combine the anti-proliferative effect of CUR-BF<sub>2</sub> and CUR compounds with anti-inflammatory benefits of non-steroidal anti-inflammatory drugs (NSAIDs), a library of the <i>bis</i>- and <i>mono</i>-NSAID/CUR-BF<sub>2</sub> and NSAID/CUR conjugates were synthesized by coupling flufenamic acid, flurbiprofen, naproxen, indomethacin, and ibuprofen to diversely substituted hydroxy-benzaldehydes via an ester linkage, and by subsequent reaction with acetylacetone-BF<sub>2</sub> to form the <i>bis</i>- and the <i>mono</i>-NSAID/CUR-BF<sub>2</sub> adducts. Since conversion to NSAID/CUR by the previously developed decomplexation protocol showed limited success, a set of NSAID/CUR conjugates were independently prepared by directly coupling the NSAIDs with parent curcumin. The <i>bis</i>-NSAID/CUR-BF<sub>2</sub> and <i>bis</i>-NSAID-CUR hybrids exhibited low cytotoxicity in NCI-60 assay, and in independent cell viability assay on colorectal cancer (CRC) cells (HCT116, HT29, DLD-1, RKO, SW837, CaCo2) and in normal CR cells (CCD841CoN). By contrast, the mono-naproxin and mono-flurbiprofen CUR-BF<sub>2</sub> adducts exhibited remarkable anti-proliferative and apoptopic activity in NCI-60 assay most notably against HCT-116 (colon), OVCAR-3 (ovarian), and ACHN (renal) cells. Computational molecular docking calculations showed favorable binding energies to HER2, VEGFR2, BRAF, and Bcl-2 as well as to COX-1 and COX-2, which in several cases exceeded known inhibitors. The main interactions between the ligands and the proteins were hydrophobic, although several hydrogen bonds were also observed. A sub-set of six compounds that had exhibited little or no cytotoxicity were tested for their anti-inflammatory response with THP-1 human macrophages in comparison to parent NSAIDs or parent curcumin.
Composition and therapeutic utility of conotoxins from genus Conus. Patent status 1996 - 2000 (2001)

With an exponentially increasing body of scientific evidence pointing toward the potential of conotoxins for treatment of a wide variety of nervous system and associated neurological disorders, there has been an explosion of activity in this patent area with more than eighty new patents and PCT publications in the past five years. With the emergence of ziconotide (SNX-111, ω-conotoxin MVIIA) as the first clinically used conotoxin for treatment of a neurological disorder, the first part of the new millennium is likely to see many more new filings in this field. The majority of the applications from this period focus on those classes of conopeptides that interact with nicotinic acetylcholine receptors (nAChRs) together with those that block voltage-gated ion channels. This arena has to date been dominated by three research groups: Neurex (a wholly-owned subsidiary of Elan, South San Francisco, CA, USA), Xenome and the Institute for Molecular Bioscience (IMB), University of Queensland (Melbourne, Australia) and Cognetix (Salt Lake City, UT, USA) together with the University of Utah Research Foundation and the Salk Institute for Biological Studies (La Jolla, CA, USA).
Chimeric Phage Lysins Act Synergistically with Lysostaphin To Kill Mastitis-Causing Staphylococcus aureus in Murine Mammary Glands (2012)

Staphylococci cause bovine mastitis, with Staphylococcus aureus being responsible for the majority of the mastitis-based losses to the dairy industry (up to $2 billion/annum). Treatment is primarily with antibiotics, which are often ineffective and potentially contribute to resistance development. Bacteriophage endolysins (peptidoglycan hydrolases) present a promising source of alternative antimicrobials. Here we evaluated two fusion proteins consisting of the streptococcal λSA2 endolysin endopeptidase domain fused to staphylococcal cell wall binding domains from either lysostaphin (λSA2-E-Lyso-SH3b) or the staphylococcal phage K endolysin, LysK (λSA2-E-LysK-SH3b). We demonstrate killing of 16 different S. aureus mastitis isolates, including penicillin-resistant strains, by both constructs. At 100 μg/ml in processed cow milk, λSA2-E-Lyso-SH3b and λSA2-E-LysK-SH3b reduced the S. aureus bacterial load by 3 and 1 log units within 3 h, respectively, compared to a buffer control. In contrast to λSA2-E-Lyso-SH3b, however, λSA2-E-LysK-SH3b permitted regrowth of the pathogen after 1 h. In a mouse model of mastitis, infusion of 25 μg of λSA2-E-Lyso-SH3b or λSA2-E-LysK-SH3b into mammary glands reduced S. aureus CFU by 0.63 or 0.81 log units, compared to >2 log for lysostaphin. Both chimeras were synergistic with lysostaphin against S. aureus in plate lysis checkerboard assays. When tested in combination in mice, λSA2-E-LysK-SH3b and lysostaphin (12.5 μg each/gland) caused a 3.36-log decrease in CFU. Furthermore, most protein treatments reduced gland wet weights and intramammary tumor necrosis factor alpha (TNF-α) concentrations, which serve as indicators of inflammation. Overall, our animal model results demonstrate the potential of fusion peptidoglycan hydrolases as antimicrobials for the treatment of S. aureus-induced mastitis.
Immunohistochemical demonstration of membrane cofactor protein (MCP) of complement in normal and diseased kidney tissues (1993)

The immunohistochemically stained membrane cofactor protein of complement (MCP/CD46), one of the complement regulatory proteins, was up-regulated in some diseased kidney tissues. MCP in diseased kidneys was strongly concentrated along the glomerular capillary walls as well as in the mesangial regions, while MCP in normal kidneys was weakly detected in all glomerular structural cells and in the epithelial cells of tubules. Since the enhanced staining was noted in those areas where depositions of C3b/C3c occurred, ongoing complement reaction might be responsible for the up-regulation of MCP expression. MCP expression may be up-regulated by complement fragments generated during complement activation in glomerulonephritis. Furthermore, anti-MCP staining was stronger in intensity in patients with moderate to massive proteinuria, indicating that up-regulation of MCP expression could be directly correlated to the kidney damage.
ETS rearrangements in prostate cancer (2012)

Prostate cancer is a clinically and molecularly heterogeneous disease. Understanding the biologic underpinning of prostate cancer is necessary to best determine how biology is associated with the risk of disease progression and how this understanding might provide insight into the development of novel therapeutic approaches. The focus of this review is on the recently identified common ETS and non-ETS gene rearrangements in prostate cancer. Although multiple molecular alterations have been detected in prostate cancer, a basic understanding of gene fusion prostate cancer should help explain the clinical and biologic diversity, providing a rationale for a molecular subclassification of the disease.
Floating Substrate Passive Voltage Contrast (FSPVC) (2006)

Abstract Light emission [1,2] and passive voltage contrast (PVC) [3,4] are common failure analysis tools that can quickly identify and localize gate oxide short sites. In the past, PVC was not used on electrically floating substrates or SOI (silicon-on-insulator) devices due to the conductive path needed to “bleed off” charge. In PVC, the SEM’s primary beam induces different equilibrium potentials on floating versus grounded (0 V) conductors, thus generating different secondary electron emission intensities for fault localization. Recently we obtained PVC signals on bulk silicon floating substrates and SOI devices. In this paper, we present details on identifying and validating gate shorts utilizing this Floating Substrate PVC (FSPVC) method.
Three-Dimensional Vertical-Bloch-Line Memory System (1994)

In proposed magnetic memory system without moving parts, data is stored in stack of two-dimensional vertical-Bloch-line (VBL) memory chips or modules. similar to one described in Three-Dimensional Magnetic-Bubble System (NPO-18533). Each VBL module in this memory system silimar to module described in Vertical-Bloch-Line Memory (NPO-18467). Advantages include high storage density, high speed, nonvolatility, and insensitivity to ionizing radiation.
Cross-Linked Protein Nanofilter with Antibacterial Properties for Multifunctional Air Filtration (2017)

Development of high-performance nanomaterials with not only strong ability to trap the pollutants but also good structure stability under varying environmental conditions is a critical need for air-filtration applications. However, it has been very challenging for a filtering material to simultaneously realize multifunctional air filtration and good environmental stability. Here, based on our previous studies on protein-based nanofilters, we report a cross-linked protein nanofabric to address this challenging issue. It is found that cross-linked protein nanofabrics can significantly improve the structure stability against different moisture levels and temperatures, while maintaining the multifunctional filtration performance. Moreover, it is demonstrated that the cross-linked protein nanomaterials also possess antibacterial properties, such as Shewanella oneidensis bacteria, further improving the environmental stability. The effects of cross-linking with different loadings of cross-linking agent on the structure stability and filtration performance are further investigated at different humidity levels and temperatures. This study provides a cost-effective solution for advanced "green" nanomaterials with excellent performance in both filtration functions and structure stability under varying environment.