gebhart/patrepeval huggingface dataset:
Single-cut genome editing restores dystrophin expression in a new mouse model of muscular dystrophy (2017)

Duchenne muscular dystrophy (DMD) is a severe, progressive muscle disease caused by mutations in the dystrophin gene. The majority of DMD mutations are deletions that prematurely terminate the dystrophin protein. Deletions of exon 50 of the dystrophin gene are among the most common single exon deletions causing DMD. Such mutations can be corrected by skipping exon 51, thereby restoring the dystrophin reading frame. Using clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9), we generated a DMD mouse model by deleting exon 50. These ΔEx50 mice displayed severe muscle dysfunction, which was corrected by systemic delivery of adeno-associated virus encoding CRISPR/Cas9 genome editing components. We optimized the method for dystrophin reading frame correction using a single guide RNA that created reframing mutations and allowed skipping of exon 51. In conjunction with muscle-specific expression of Cas9, this approach restored up to 90% of dystrophin protein expression throughout skeletal muscles and the heart of ΔEx50 mice. This method of permanently bypassing DMD mutations using a single cut in genomic DNA represents a step toward clinical correction of DMD mutations and potentially those of other neuromuscular disorders.
Sputter parameters and magnetic properties of permalloy for thin film heads (1986)

The sputter parameters of Permalloy for the magnetic poles of thin film heads are optimized. The experiments are carried out in a standard RF diode system with RF bias. Argon nitrogen mixtures are used as sputter gas. The anisotropy field strength H <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">k</inf> keeps relatively constant for all parameter variations, whereas the coercivity drops when the nitrogen content of the sputter gas is raised from 0 % to more than 1 %. The saturation magnetostriction λ <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">s</inf> is very sensitive on the target composition. Changing from 76.6 to 82.4 wt % Ni causes a λ <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">s</inf> variation from +5×10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-6</sup> to -2.5×10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-6</sup> . Higher bias voltages result in more negative λ <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">s</inf> values. Additionally λ <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">s</inf> can be controlled over a relatively wide range (about 1.6×10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-6</sup> ) by the nitrogen content (0-5 %) of the sputter gas. About 1.3 wt % in composition of the target can be compensated by this nitrogen doping. X-ray investigations show that the different values are caused by composition variations in the film. Depending on whether /λ <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">s</inf> /< 1×10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-6</sup> or /λ <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">s</inf> / > 1×10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-6</sup> mainly two different types of domain structures were observed on patterned pole structures.
Expression of a maize proteinase inhibitor gene is induced in response to wounding and fungal infection: systemic wound‐response of a monocot gene (1994)

The isolation and characterization of cDNA and genomic clones encoding a proteinase inhibitor protein (MPI) in maize is reported. Accumulation of the MPI mRNA is induced in response to fungal infection in germinating maize embryos. The expression pattern of the MPI gene, in healthy and fungal infected maize tissues, was examined and compared with the expression pattern of a gene that codes for a pathogenesis-related protein (the PRms protein) from maize. These two genes are induced by fungal infection, however different signals trigger their activation. Accumulation of the proteinase inhibitor mRNA is more a consequence of the wound produced by the penetration and colonization of the host tissues by the pathogen, than the result of a direct molecular recognition of the pathogen by the plant, as is the case for the induction of the PRms gene. Wounding, or treatment with abscisic acid or methyl jasmonate, stimulate MPI mRNA accumulation, but not PRms mRNA accumulation. Local and systemic induction of the MPI gene expression in response to wounding occurs in maize plants. To the authors' knowledge, this is the first example of a gene from a monocotyledonous species that clearly shows a systemic wound response. The possible functional implications for the existence of different signal transduction pathways that simultaneously activate a battery of defense mechanisms against potential pathogens are discussed.
Determination of ligand-binding specificity by alternative splicing: two distinct growth factor receptors encoded by a single gene. (1992)

Expression cDNA cloning and structural analysis of the human keratinocyte growth factor receptor (KGFR) revealed identity with one of the fibroblast growth factor (FGF) receptors encoded by the bek gene (FGFR-2), except for a divergent stretch of 49 amino acids in their extracellular domains. Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. Genomic analysis of the bek gene revealed two alternative exons responsible for the region of divergence between the two receptors. The KGFR transcript was specific to epithelial cells, and it appeared to be differentially regulated with respect to the alternative FGFR-2 transcript. Thus, two growth factor receptors with different ligand-binding specificities and expression patterns are encoded by alternative transcripts of the same gene.
A reusable BIST with software assisted repair technology for improved memory and IO debug, validation and test time (2014)

As silicon integration complexity increases with 3D stacking and Through-Silicon-Via (TSV), so does the occurrence of memory and IO defects and associated test and validation time. This ultimately leads to an overall cost increase. On a 14nm Intel SOC, a reusable BIST engine called Converged-Pattern-Generator-Checker (CPGC) are architected to detect memory and IO defects, and combined with the software assisted repair technology to automatically repair memory cell defects on 3D stacked Wide-IO DRAM. Additionally, we also present the CPGC gate count, power, simulation, and silicon results. The reusable CPGC IP is designed to connect to a standard IP interface, which enables a quick turn-key SOC development cycle. Silicon results show CPGC can speed up validation by 5x, improve test time from minutes down to seconds, and decrease debug time by 5x including root-cause of boot failures of the memory interface. CPGC is also used in memory training and initialization, which makes it a critical part of Intel SOC.
Memory Organization for a Cubic Frame Buffer (1986)

A special memory organization of a cubic voxel-based frame buffer is presented. The memory of voxels is divided into n modules of voxels each. The k-th module groups together all the principal diagonal planes within the cubic frame buffer, that their sequential index is k mod (n ). This organization guarantees that all the n voxels which constitute a row in any direction parallel to the axes reside in different modules, permitting the retrieval of all the voxels of a row simultaneously. This memory layout is the heart of a voxel-based CUBE Architecture for three-dimensional graphics. The architecture employs three processors which access the memory, to input, manipulate, and view the image within the memory. The unique memory organization enables these processors and the entire system to cope with real-time constraints.
Transgenic mice expressing mutant forms VCP/p97 recapitulate the full spectrum of IBMPFD including degeneration in muscle, brain and bone (2010)

Inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD) is a dominantly inherited degenerative disorder caused by mutations in the valosin-containing protein (VCP) gene. VCP (p97 in mouse, TER94 in Drosophila melanogaster and CDC48 in Saccharomyces cerevisiae) is a highly conserved AAA(+)-ATPase that regulates a wide array of cellular processes. The mechanism of IBMPFD pathogenesis is unknown. Towards elucidating the pathogenic mechanism we have developed and characterized transgenic mice with ubiquitous expression of wild-type and disease-causing versions of human VCP/p97. Here, we report that mice expressing VCP/p97 harboring the mutations R155H or A232E develop pathology that is limited to muscle, brain and bone, recapitulating the spectrum of disease in humans with IBMPFD. The mice exhibit progressive muscle weakness and pathological examination of muscle shows classic characteristics of inclusion body myopathy including rimmed vacuoles and TDP-43 pathology. The mice exhibit abnormalities in behavioral testing and pathological examination of the brain shows widespread TDP-43 pathology. Furthermore, radiological examination of the skeleton reveals that mutant mice develop severe osteopenia accompanied by focal lytic and sclerotic lesions in vertebrae and femur. In vitro studies indicate that mutant VCP causes inappropriate activation of the NF-kappaB signaling cascade, which could contribute to the mechanism of pathogenesis in multiple tissues including muscle, bone and brain.
Synthetische Analoga von niedermolekularen Spinnentoxinen mit Acyl‐polyamin‐Struktur (1993)

Synthetic Analogues of Low‐Molecular‐Weight Acyl‐polyamine Spider Toxins Low‐molecular‐weight spider and wasp toxins are selective inhibitors of glutamate receptors of the central nervous system and consist of a polyamine backbone and one or several carboxylic acids and/or amino acids linked by a peptide‐like bond. The syntheses of twelve analogues of spider and wasp toxins are described ( 10a – c , 15a – c , 20a – c , 25a – c ) having the general structure of acyl, arylacyl, or heteroarylacyl → DL ‐alanyl → ω‐aminoacyl → N 1 ‐spermidine, with variation in the acyl and the ω‐aminoacyl part.
Nerve growth factor NT-5 induce increased thermal sensitivity of cutaneous nociceptors in vitro (1996)

1. Perfusion of the receptive field (RF) of C- or A delta-fiber nociceptors with nerve growth factor (NGF) in an in vitro preparation of the rat saphenous nerve with functionally attached skin induced a significant decrease in heat threshold without changing mechanical or cold sensitivity. 2. NGF-induced thermal sensitization was absent after saline perfusion and in skin taken from mast-cell depleted animals, hence confirming a role for mast cells in NGF-induced thermal hyperalgesia. 3. Neurotrophin-5 (NT-5) also induced a small but significant reduction in heat threshold without affecting mechanical sensitivity. It is speculated that NT-5 exerts its action either directly on the trkA receptor, as with NGF or alternatively through trkB receptors located on sympathetic efferents or on small diameter afferents.
Alzheimer's Disease Drug Discovery from Herbs: Neuroprotectivity from β -Amyloid (1-42) Insult (2007)

Selective herbs may be potentially important resources to discover drug candidates against the onset of Alzheimer's disease.
Targeted Massively Parallel Sequencing of Maternal Plasma DNA Permits Efficient and Unbiased Detection of Fetal Alleles (2010)

BACKGROUND Massively parallel sequencing has recently been used in noninvasive prenatal diagnosis. The current costs of this technology are still relatively expensive, however, and sample throughput is still relatively low when it is used as a molecular diagnostic tool. Rather than nonselectively sequencing the genome, target enrichment provides a logical approach for more efficient and cost-effective massively parallel sequencing because it increases the proportion of informative data from the targeted region(s). Existing applications of targeted sequencing have mainly been qualitative analyses of genomic DNA. In this study, we investigated its applicability in enriching selected genomic regions from plasma DNA and the quantitative performance of this approach. METHODS DNA was extracted from plasma samples collected from 12 pregnant women carrying female fetuses. The SureSelect Target Enrichment System (Agilent Technologies) was used to enrich for exons on chromosome X. Plasma DNA libraries with and without target enrichment were analyzed by massively parallel sequencing. Genomic DNA samples of the mother and fetus for each case were genotyped by microarray. RESULTS For the regions targeted by the enrichment kit, the mean sequence coverage of the enriched samples was 213-fold higher than that of the nonenriched samples. Maternal and fetal DNA molecules were enriched evenly. After target enrichment, the coverage of fetus-specific alleles within the targeted region increased from 3.5% to 95.9%. CONCLUSIONS Targeted sequencing of maternal plasma DNA permits efficient and unbiased detection of fetal alleles at genomic regions of interest and is a powerful method for measuring the proportion of fetal DNA in a maternal plasma sample.
Phenolic Acids in Berries, Fruits, and Beverages (2006)

The contents of soluble and total phenolic acids were analyzed in samples of 29 berries and berry products, 24 fruits and fruit peels, and 12 beverages. Variation of phenolic acids in berries was also studied. Soluble phenolic acids were extracted with methanolic acetic acid, and a tentative quantification was performed by high-performance liquid chromatography (HPLC). The total phenolic acid content was determined by HPLC after alkaline and acid hydrolyses. The content of total phenolic acids as aglycones in the above samples varied from 0 (pear cider) to 103 mg/100 g fresh weight (rowanberry). Besides rowanberry, the best phenolic acid sources among berries were chokeberry (96 mg/100 g), blueberry (85 mg/100 g), sweet rowanberry (75 mg/100 g), and saskatoon berry (59 mg/100 g). Among fruits, the highest contents (28 mg/100 g) were determined in dark plum, cherry, and one apple variety (Valkea Kuulas). Coffee (97 mg/100 g) as well as green and black teas (30-36 mg/100 g) were the best sources among beverages. Caffeic acid dominated in all of these samples except in tea brews. Variation in the phenolic acid contents of the berries was either small or moderate.
DTASelect and Contrast:  Tools for Assembling and Comparing Protein Identifications from Shotgun Proteomics (2002)

The components of complex peptide mixtures can be separated by liquid chromatography, fragmented by tandem mass spectrometry, and identified by the SEQUEST algorithm. Inferring a mixture's source proteins requires that the identified peptides be reassociated. This process becomes more challenging as the number of peptides increases. DTASelect, a new software package, assembles SEQUEST identifications and highlights the most significant matches. The accompanying Contrast tool compares DTASelect results from multiple experiments. The two programs improve the speed and precision of proteomic data analysis.
Molecular imaging of gene expression and protein function in vivo with PET and SPECT (2002)

Molecular imaging is broadly defined as the characterization and measurement of biological processes in living animals, model systems, and humans at the cellular and molecular level using remote imaging detectors. One underlying premise of molecular imaging is that this emerging field is not defined by the imaging technologies that underpin acquisition of the final image per se, but rather is driven by the underlying biological questions. In practice, the choice of imaging modality and probe is usually reduced to choosing between high spatial resolution and high sensitivity to address a given biological system. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) inherently use image-enhancing agents (radiopharmaceuticals) that are synthesized at sufficiently high specific activity to enable use of tracer concentrations of the compound (picomolar to nanomolar) for detecting molecular signals while providing the desired levels of image contrast. The tracer technologies strategically provide high sensitivity for imaging small-capacity molecular systems in vivo (receptors, enzymes, transporters) at a cost of lower spatial resolution than other technologies. We review several significant PET and SPECT advances in imaging receptors (somatostatin receptor subtypes, neurotensin receptor subtypes, alpha(v)beta(3) integrin), enzymes (hexokinase, thymidine kinase), transporters (MDR1 P-glycoprotein, sodium-iodide symporter), and permeation peptides (human immunodeficiency virus type 1 (HIV-1) Tat conjugates), as well as innovative reporter gene constructs (herpes simplex virus 1 thymidine kinase, somatostatin receptor subtype 2, cytosine deaminase) for imaging gene promoter activation and repression, signal transduction pathways, and protein-protein interactions in vivo.
Picture archiving and communication systems: an overview. (1992)

Organizational techniques that enable small departments to function efficiently often fail as departments become larger. With the recent growth in imaging technology, the capacity of film-based systems to meet the increasing needs of radiology departments has decreased. Electronic picture archiving and communication systems (PACS) have been developed in an attempt to provide economical storage, rapid retrieval of images, access to images acquired with multiple modalities, and simultaneous access at multiple sites. Input to a PACS may come from digital or analog sources (when the latter have been digitized). A PACS consists primarily of an image acquisition device (an electronic gateway to the system), data management system (a specialized computer system that controls the flow of information on the network), image storage devices (both short- and long-term archives), transmission network (which serves local or wide areas), display stations (which include a computer, text monitor, image monitors, and a user interface), and devices to produce hard-copy images (currently, a multiformat or laser camera). The goals of PACS are to improve operational efficiency while maintaining or improving diagnostic ability.
Nanoparticles and microparticles for drug and vaccine delivery. (1996)

Nanoparticles are polymeric particles in the nanometer size range whereas microparticles are particles in the micrometre size range. Both types of particle are used as drug carriers into which drugs or antigens may be incorporated in the form of solid solutions or solid dispersions or onto which these materials may be absorbed or chemically bound. These particles have been shown to enhance the delivery of certain drugs across a number of natural and artificial membranes. In addition, the particles were shown to accumulate in areas of the intestine that appear to be the Peyer's patches. Possibly because of the combination of both effects these particles were able to significantly improve the bioavailability of some drugs after peroral administration in comparison with solutions. Recently nanoparticles coated with polysorbate 80 enabled the passage of small peptides and other drugs across the blood-brain barrier and the exhibition of a pharmacological effect after intravenous injection. Without the use of this type of nanoparticles the drugs did not cross this barrier and yielded no effect.
Realization of the therapeutic potential of CTLA-4 blockade in low-dose chemotherapy-treated tumor-bearing mice. (1998)

CTLA-4 blockade has been shown by other investigators [D. R. Leach, et al., Science (Washington DC), 271: 1734-1736, 1996; and Y-F. Yang, et al., Cancer Res., 57: 4036-4041, 1997] to retard tumor growth in selected tumor systems. Here, we show that CTLA-4 blockade alone was ineffective in retarding tumor growth in the murine MOPC-315 tumor system. Yet, CTLA-4 blockade offered significant therapeutic benefits to MOPC-315 tumor bearers when combined with a subtherapeutic dose of the chemotherapeutic agent melphalan, which was previously shown (L. Gorelik, et al., Cancer Immunol. Immunother., 39: 117-126, 1994) to shift the cytokine profile in the tumor bearers toward type-1 cytokines. In addition, we show here that anti-CTLA-4 monoclonal antibody enhanced antitumor cytotoxicity when the anti-CTLA-4 monoclonal antibody was added to stimulation cultures of spleen cells from low-dose melphalan-treated MOPC-315 tumor-bearing mice but not from untreated tumor-bearing mice. These results suggest that the therapeutic benefits of CTLA-4 blockade depend on the ability of drugs such as melphalan to promote an immunogenic environment by altering the cytokine profile of tumor-specific T cells.
Synthesis, cellular location, and immunogenicity of bovine herpesvirus 1 glycoproteins gI and gIII expressed by recombinant vaccinia virus (1989)

Two of the major glycoproteins of bovine herpesvirus 1 (BHV-1) are gI, a polypeptide complex with apparent molecular weights of 130,000, 74,000, and 55,000, and gIII (a 91,000-molecular-weight [91K] glycoprotein), which also exists as a 180K dimer. Vaccinia virus (VAC) recombinants were constructed which carry full-length gI (VAC-I) or gIII (VAC-III) genes. The genes for gI and gIII were each placed under the control of the early VAC 7.5K gene promoter and inserted within the VAC gene for thymidine kinase. The recombinant viruses VAC-I and VAC-III retained infectivity and expressed both precursor and mature forms of glycoproteins gI and gIII. The polypeptide backbones, partially glycosylated precursors, and mature gI and gIII glycoproteins were indistinguishable from those produced in BHV-1-infected cells. Consequently, they were apparently cleaved, glycosylated, and transported in a manner similar to that seen during authentic BHV-1 infection, although the processing efficiencies of both gI and gIII were generally higher in recombinant-infected cells than in BHV-1-infected cells. Immunofluorescence studies further demonstrated that the mature gI and gIII glycoproteins were transported to and expressed on the surface of cells infected with the respective recombinants. Immunization of cattle with recombinant viruses VAC-I and VAC-III resulted in the induction of neutralizing antibodies to BHV-1, which were reactive with authentic gI and gIII. These data demonstrate the immunogenicity of VAC-expressed gI and gIII and indicate the potential of these recombinant glycoproteins as a vaccine against BHV-1.