gebhart/patrepeval huggingface dataset:
An intronic structure enabled by a long-distance interaction serves as a novel target for splicing correction in spinal muscular atrophy (2013)

Here, we report a long-distance interaction (LDI) as a critical regulator of alternative splicing of Survival Motor Neuron 2 (SMN2) exon 7, skipping of which is linked to spinal muscular atrophy (SMA), a leading genetic disease of children and infants. We show that this LDI is linked to a unique intra-intronic structure that we term internal stem through LDI-1 (ISTL1). We used site-specific mutations and Selective 2'-Hydroxyl Acylation analyzed by Primer Extension to confirm the formation and functional significance of ISTL1. We demonstrate that the inhibitory effect of ISTL1 is independent of hnRNP A1/A2B1 and PTB1 previously implicated in SMN2 exon 7 splicing. We show that an antisense oligonucleotide-mediated sequestration of the 3' strand of ISTL1 fully corrects SMN2 exon 7 splicing and restores high levels of SMN and Gemin2, a SMN-interacting protein, in SMA patient cells. Our results also reveal that the 3' strand of ISTL1 and upstream sequences constitute an inhibitory region that we term intronic splicing silencer N2 (ISS-N2). This is the first report to demonstrate a critical role of a structure-associated LDI in splicing regulation of an essential gene linked to a genetic disease. Our findings expand the repertoire of potential targets for an antisense oligonucleotide-mediated therapy of SMA.
SNF2-Related CBP Activator Protein (SRCAP) Functions as a Coactivator of Steroid Receptor-Mediated Transcription through Synergistic Interactions with CARM-1 and GRIP-1 (2003)

SRCAP (SNF2-related CBP activator protein) is a 350-kDa protein that shares homology with the SNF2 family of proteins whose members function in various aspects of transcriptional regulation. In various cell types, SRCAP is found in distinct multiprotein complexes that include proteins found in SWI/SNF chromatin remodeling complexes. SRCAP was identified by its ability to bind to CBP and was found to potentiate the ability of CBP to activate transcription. Studies in our laboratory have demonstrated that SRCAP functions as a coactivator for CREB-mediated transcription of a number of promoters, including that of the phosphoenolpyruvate carboxykinase gene. Our current studies demonstrate that SRCAP enhances phosphoenolpyruvate carboxykinase promoter transcription induced by glucocorticoids. SRCAP also enhances glucocorticoid receptor-mediated transcription of a simple promoter containing only two glucocorticoid response elements, indicating that SRCAP functions as a glucocorticoid receptor coactivator. In similar studies, SRCAP was also found to serve as a coactivator for the androgen receptor. SRCAP exhibits synergistic activation with nuclear receptor coactivators and functionally interacts in vivo with glucocorticoid receptor-interacting protein-1 and coactivator-associated arginine methyltransferase-1. We propose that SRCAP, by virtue of its ability to interact with CBP, functions as a coactivator to regulate transcription initiated by several signaling pathways.
Overview of NASA Glenn Seal Program (2003)

The Seal Team is divided into four primary areas. These areas include turbine engine seal development, structural seal development, acoustic seal development, and adaptive seal development. The turbine seal area focuses on high temperature, high speed shaft seals for secondary air system flow management. The structural seal area focuses on high temperature, resilient structural seals required to accommodate large structural distortions for both space- and aero-applications. Our goal in the acoustic seal project is to develop non-contacting, low leakage seals exploiting the principles of advanced acoustics. We are currently investigating a new acoustic field known as Resonant Macrosonic Synthesis (RMS) to see if we can harness the large acoustic standing pressure waves to form an effective air-barrier/seal. Our goal in the adaptive seal project is to develop advanced sealing approaches for minimizing blade-tip (shroud) or interstage seal leakage. We are planning on applying either rub-avoidance or regeneration clearance control concepts (including smart structures and materials) to promote higher turbine engine efficiency and longer service lives.
C1-CBP-vancomycin: Impact of a Vancomycin C-Terminus Trimethylammonium Cation on Pharmacological Properties and Insights into Its Newly Introduced Mechanism of Action (2019)

C1-CBP-vancomycin (<b>3</b>) was examined alongside CBP-vancomycin for susceptibility to acquired resistance upon serial exposure against two vancomycin-resistant enterococci strains where its activity proved more durable and remarkably better than many current therapies. Combined with earlier studies, this observation confirmed an added mechanism of action was introduced by incorporation of the trimethylammonium cation and that C1-CBP-vancomycin exhibits activity against vancomycin-resistant organisms through two synergistic mechanisms of action, both independent of d-Ala-d-Ala/d-Lac binding. New insights into this added mechanism of action, induced cell membrane permeabilization, can be inferred from studies that show added exogenous lipoteichoic acid reduces antimicrobial activity, rescues bacteria cell growth inhibition, and blocks induced cell permeabilization properties of C1-CBP-vancomycin, suggesting a direct binding interaction with embedded teichoic acid is responsible for the added mechanism of action and enhanced antimicrobial activity. Further studies indicate that the trimethylammonium cation does not introduce new liabilities in common pharmacological properties of the analogue and established that <b>3</b> is well tolerated in mice, displays substantial PK improvements over both vancomycin and CBP-vancomycin, and exhibits in vivo efficacy against a challenging multidrug-resistant and vancomycin-resistant <i>S. aureus</i> strain that is representative of the resistant pathogens all fear will emerge in the general population.
Strain-Transcending Inhibitory Antibodies against Homologous and Heterologous Strains of Duffy Binding Protein region II (2016)

Duffy binding protein region II (DBPII) is a promising vaccine candidate against vivax malaria. However, polymorphisms of DBPII are the major obstacle to designing a successful vaccine. Here, we examined whether anti-DBPII antibodies from individual P. vivax exposures provide strain-transcending immunity and whether their presence is associated with DBPII haplotypes found in patients with acute P. vivax. The ability of antibodies to inhibit DBL-TH-erythrocyte binding was tested by COS7 erythrocyte binding inhibition assay. Seven samples of high responders (HR) were identified from screening anti-DBPII levels. HR no.3 and HR no.6 highly inhibited all DBL-TH binding to erythrocytes, by >80%. Antibodies from these two patients' plasma had the potential to be broadly inhibitory against DBL-TH1, -TH2, -TH6, -TH7, -TH8 and -TH9 haplotypes when plasma was serially diluted from 1:500 to 1:2000. To further examine the association of DBPII haplotypes and the ability of antibodies to broadly inhibit DBL-TH variants, the individual samples underwent sequencing analysis and the inhibitory function of the anti-DBPII antibodies was tested. The patterns of DBPII polymorphisms in acute patients were classified into two groups, DBPII Sal I (55%) and DBL-TH variants (45%). Plasma from Sal I and DBPII-TH patients who had the highest inhibition against Sal I or DBL-TH4 and -TH5 was serially diluted from 1:500 to 1:2000 and their inhibitory capacity was tested against a panel of DBL-TH haplotypes. Results provided evidence of both strain-transcending inhibition as well as strain-specific inhibition by antibodies that blocked erythrocyte binding against some DBL-TH variants and against homologous alleles. This study demonstrated broad inhibition by anti-DBPII antibodies against DBL-TH haplotypes in natural P. vivax exposed individuals. The identification of conserved epitopes among DBL-TH may have implications for vaccine development of a DBPII-based vaccine against diverse P. vivax infections.
Making image quality assessment robust (2012)

We develop a robust framework for natural scene statistic (NSS) model based blind image quality assessment (IQA). The robustified IQA model utilizes a robust statistics approach based on L-moments. Such robust statistics based approaches are effective when natural or distorted images deviate from assumed statistical models, and achieves better prediction performance on distorted images relative to human subjective judgments. We also show how robustifying the model makes IQA approach resilient against deviation in model assumptions, small variations in the distortions and amount of data the model is trained on.
Parallel Algorithm for Precise Navigation Using Black-Box Forward Model and Motion Primitives (2019)

Reliable robot navigation is an active research topic for many real-world applications, such as the automation of industrial equipment, where machines with arbitrary shapes need to navigate very close to obstacles to perform efficiently. We have developed a new planning architecture that allows wheeled vehicles to navigate safely in cluttered environments. Our method belongs to the Model Predictive Control (MPC) family of local planning algorithms. It works in the space of two-dimensional occupancy grids and plans in motor command space using a black box forward model for state inference. Our method has several properties that make it well-suited for commercial applications: itis deterministic, computationally efficient, runs in constant time, and can be used on platforms of arbitrary shape and drive type. We provide a detailed description of the algorithm, showcase its application on real robots, and compare it with other state-of-the-art planning algorithms.
Computer aided diagnosis: design and development of a system for stroke MR image processing (2006)

We designed and developed a CAD system for acute ischemic stoke MR image processing. This CAD system supports the thrombolysis algorithm, and provides rapid, automatic and quantitative assessment. The size of the infarct versus that of MCA territory and the diffusion-perfusion mismatch are calculated rapidly, automatically and quantitatively. For image quantification, two brain atlases are employed: atlas of anatomy and atlas of blood supply territories. Atlas-assisted analysis provides the complete list of anatomical structures and blood supply territories along with their volume and percentage contributions to the infarct and penumbra. Processing of MR images is very fast, as almost all operations are near real-time. The proposed approach shifts the paradigm in stroke image processing from a 2D visual inspection of the individual scans and maps to an atlas-assisted quantification and simultaneous visualization of multiple 2D and 3D images. Our stroke CAD system facilitates and speeds up analysis of data as well as supports decision making. It is potentially useful in diagnosis and research, particularly, for clinical trials.
TH-D-332-09: Development of a Search Method to Find Lost Chest Radiographs in PACS Server (2008)

Purpose: Misfiled cases in the PACS environment may create serious medical accidents in the hospitals and medical centers. The purpose of this study was to show a potential usefulness of an automated search method by use of biological fingerprints 2), i.e., some parts of chest radiographs, and image-matching technique to find lost chest radiographs in a large database. Method and Materials: We employed five biological fingerprints in a chest radiograph such as cardiac shadow, lung apex, the superior mediastinum, the right lower lung, and a thoracic field. To find a lost image in a large database, biological fingerprints were extracted from a target image, i.e., the previous image of the same patient. Each of the biological fingerprints of the target image was used as a template for determination of the correlation value with the corresponding biological fingerprints in the current chest radiograph in the database. Our database used in this study included 36,228 patients with PA digital chest radiographs including 20,278 females and 15,950 males. Forty-six target images were selected randomly, and used hypothetically as lost images to examine the potential usefulness of our method based on the biological fingerprints and image-matching technique. Results: By use of all of images in our database, 78.3% (36/46) of the target images were correctly identified as the same patient's image by our method. Moreover, it was possible to identify 8.7% (4/46) of the additional target images correctly, when previous images with the top two to five correlation index were examined. These results appear to be promising in finding a patient with the lost images based on comparison with a large number of images. Conclusion: Our method by use of biological fingerprints and image-matching technique has potential usefulness to find the lost chest radiographs automatically in the PACS server.
The 'staggering switch': an electronically controlled optical packet switch (1993)

An architecture and implementation issues for an almost-all-optical packet switch that does not rely on recirculating loops for storage implementation are presented. The architecture is based on two rearrangeably nonblocking stages interconnected by optical delay lines with different amounts of delay. The probability of loss and the switch latency as a function of link utilization and of the size of the switch are investigated. In general, with proper setting of the number of delay lines, the switch can achieve an arbitrarily low probability of loss. Growability patterns and extension of the design to the dense wavelength-division-multiplexing (WDM) case are also shown. In particular, an extension to the architecture whereby, through the use of WDM, the switch capability can be increased several times, with only minor changes to the switch design is discussed. Additionally, issues involving practical implementation of such a switch are considered. For example, a scheme that allows optical packet synchronization for the synchronously-operated switch is shown. Using this scheme, the switch can be a central component in the design of future all-optical, packet-switched networks.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Combinatorial Domain Hunting: An effective approach for the identification of soluble protein domains adaptable to high‐throughput applications (2006)

Exploitation of potential new targets for drug and vaccine development has an absolute requirement for multimilligram quantities of soluble protein. While recombinant expression of full-length proteins is frequently problematic, high-yield soluble expression of functional subconstructs is an effective alternative, so long as appropriate termini can be identified. Bioinformatics localizes domains, but doesn't predict boundaries with sufficient accuracy, so that subconstructs are typically found by trial and error. Combinatorial Domain Hunting (CDH) is a technology for discovering soluble, highly expressed constructs of target proteins. CDH combines unbiased, finely sampled gene-fragment libraries, with a screening protocol that provides "holistic" readout of solubility and yield for thousands of protein fragments. CDH is free of the "passenger solubilization" and out-of-frame translational start artifacts of fusion-protein systems, and hits are ready for scale-up expression. As a proof of principle, we applied CDH to p85alpha, successfully identifying soluble and highly expressed constructs encapsulating all the known globular domains, and immediately suitable for downstream applications.
Chapter 11 Semaphorin-mediated neuronal growth cone guidance (1998)

The semaphorin family contains a large number of phylogenetically conserved proteins and includes several members that have been shown to function in repulsive axon guidance. The importance of repulsive cues in path finding and target selection has now been firmly established at the cellular and molecular levels. Semaphorin III (Sema III) is a secreted protein that in vitro causes neuronal growth cone collapse and chemorepulsion of neurites, and in vivo is required for correct sensory afferent innervations and other aspects of development. The mechanism of Sema III function, however, is unknown. This chapter reviews experiments demonstrating that neuropilin- 1, a type I transmembrane protein implicated in aspects of neurodevelopment, is a Sema III receptor or component of a receptor complex. Neuropilin-1 is the founding member of a gene family, including neuropilin-2, a related protein that is expressed in overlapping, yet distinct, populations of neurons in rat embryonic nervous system. These experiments suggest that the neuropilins play a critical role in imparting specificity to the action of semaphorins during neurodevelopment. In addition, evidence is accumulating that transmembrane semaphorins also play essential roles in peripheral and CNS axon guidance events. Drosophila semaphorin I (D-Sema I) is a transmembrane protein that in vivo is required for motor and central nervous system (CNS) axon guidance events. Genetic experiments in Drosophila strongly suggest that D-Sema I also can function as a repulsive guidance cue.
Proviral Organization and Sequence Analysis of Feline Immunodeficiency Virus Isolated from a Pallas' Cat (1997)

The nucleotide sequence and genomic organization have been determined for a highly cytopathic feline immunodeficiency virus (FIV) isolated from a Pallas' cat. The 9747-bp provirus of this virus, FIV-Oma, has typical lentivirus organization with LTRs, gag, pol, and env open reading frames (ORFs), putative vif and rev ORFs, and an ORF similar to ORF2/ORFA of domestic cat FIV isolates. Although the FIV-Oma provirus is 300 to 600 bp longer than other FIV proviruses, these additional bases are distributed throughout the genome. Phylogenetic analysis of a conserved region of the pol gene suggests that FIV-Oma is more closely related to some of the puma and lion lentiviruses than it is to domestic cat FIV isolates; however, many regions of the genome exhibit extensive nucleotide sequence divergence. None of the eight molecular proviral clones isolated from a genomic library are infectious, but we have constructed an infectious, cytopathic clone of FIV-Oma from subcloned and PCR-amplified fragments of these proviral clones. This clone will be useful for identifying the genetic determinants of FIV-Oma's biological activities.
X-ray excited luminescence spectroscopy of barium fluorohalides (1989)

Photostimulated luminescence (PSL) phosphors, such as BaFBr:Eu, are currently used in x-ray screens for digital medical imaging. There is, however, little known about the mechanistic details responsible for the luminescence process in these materials. This paper describes a study of the emission mechanism in the host lattice BaFX(X=Cl, Br). Electron-hole recombination luminescence produced by x-ray irradiation has been observed. The recombination luminescence intensity is temperature dependent and yields information concerning the ionization process in these crystal lattices. This information is fundamental to the PSL process.
Flicker: Saving Refresh-Power in Mobile Devices through Critical Data Partitioning (2009)

Mobile devices are left in sleep mode for long periods of time. But even while in sleep mode, the contents of DRAM memory need to be periodically refreshed, which consumes a significant fraction of power in mobile devices. This paper introduces Flicker, an application-level technique to reduce refresh power in DRAM memories. Flicker enables developers to specify critical and non-critical data in programs and the runtime system allocates this data in separate parts of memory. The portion of memory containing critical data is refreshed at the regular refresh-rate, while the portion containing non-critical data is refreshed at substantially lower rates. This saves energy at the cost of a modest increase in data corruption in the non-critical data. Flicker thus explores a novel and interesting trade-off between energy consumption and hardware correctness. We show that many mobile applications are naturally tolerant to errors in the non-critical data, and in the vast majority of cases, the errors have little or no impact on the application’s final outcome. We also find that Flicker can save between 20-25% of the power consumed by the memory subsystem in a mobile device, with negligible impact on application performance. Flicker is implemented almost entirely in software, and requires only modest changes to the application, operating system and hardware.
SU‐GG‐I‐13: Low‐Contrast Detectability for X‐Ray Computed Tomography (2008)

Low‐contrast‐detectability (LCD) is one of the important performance parameters for computed tomography (CT). Often LCD is determined by visual inspection of low‐contrast phantom images. The testing process is gated not only by limitations of existing LCD phantoms, but also by the subjective nature of the evaluation methodology. Although statistical LCD methods were proposed, these methods often unfairly favor post‐processed images, since they measure mainly the noise characteristics in uniform portion of the phantom and do not consider the impact on LCD objects. In this paper, we present a measurement methodology that incorporates the LCD objects as part of the testing process. To overcome limited availability of low‐contrast phantoms in terms of object size and contrast level, computer simulated objects are inserted into the reconstructed uniform phantom images prior to the post‐process filtering steps. These test objects are obtained by convolving the ideal disc shaped objects with the point‐spread‐function (PSF) of the system. We also propose a LCD index that incorporates the object contrasts and noise levels of the LCD images. The index is defined as the ratio of the measured object contrast over the standard deviation of means measured over a region equal to the LCD object size. This index overcomes the shortcomings of the previously proposed statistical method in which the visibility of post‐processed low‐contrast objects are over‐estimated. Extensive phantom tests were conducted. Existing statistical‐based LCD measure was compared with the proposed LCD index, and both were judged against visual inspection of experts. Phantoms vary over different contrast, object size, scan techniques, and reconstruction kernels. Test results have shown that the proposed LCD method outperforms the existing method and correlates well with human observers. Future extension of the algorithm includes the refinement of the LCD object shape and the non‐stationary characteristics of the PSF and noise in CT systems.