gebhart/patrepeval huggingface dataset:
Overlapping functions of the myogenic bHLH genes MRF4 and MyoD revealed in double mutant mice (1998)

The myogenic basic helix-loop-helix (bHLH) genes - MyoD, Myf5, myogenin and MRF4 - exhibit distinct, but overlapping expression patterns during development of the skeletal muscle lineage and loss-of-function mutations in these genes result in different effects on muscle development. MyoD and Myf5 have been shown to act early in the myogenic lineage to establish myoblast identity, whereas myogenin acts later to control myoblast differentiation. In mice lacking myogenin, there is a severe deficiency of skeletal muscle, but some residual muscle fibers are present in mutant mice at birth. Mice lacking MRF4 are viable and have skeletal muscle, but they upregulate myogenin expression, which could potentially compensate for the absence of MRF4. Previous studies in which Myf5 and MRF4 null mutations were combined suggested that these genes do not share overlapping myogenic functions in vivo. To determine whether the functions of MRF4 might overlap with those of myogenin or MyoD, we generated double mutant mice lacking MRF4 and either myogenin or MyoD. MRF4/myogenin double mutant mice contained a comparable number of residual muscle fibers to mice lacking myogenin alone and myoblasts from those double mutant mice formed differentiated multinucleated myotubes in vitro as efficiently as wild-type myoblasts, indicating that neither myogenin nor MRF4 is absolutely essential for myoblast differentiation. Whereas mice lacking either MRF4 or MyoD were viable and did not show defects in muscle development, MRF4/MyoD double mutants displayed a severe muscle deficiency similar to that in myogenin mutants. Myogenin was expressed in MRF4/MyoD double mutants, indicating that myogenin is insufficient to support normal myogenesis in vivo. These results reveal unanticipated compensatory roles for MRF4 and MyoD in the muscle differentiation pathway and suggest that a threshold level of myogenic bHLH factors is required to activate muscle structural genes, with this level normally being achieved by combinations of multiple myogenic bHLH factors.
Yersinia pestis , the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis (1999)

Plague, one of the most devastating diseases of human history, is caused by Yersinia pestis. In this study, we analyzed the population genetic structure of Y. pestis and the two other pathogenic Yersinia species, Y. pseudotuberculosis and Y. enterocolitica. Fragments of five housekeeping genes and a gene involved in the synthesis of lipopolysaccharide were sequenced from 36 strains representing the global diversity of Y. pestis and from 12-13 strains from each of the other species. No sequence diversity was found in any Y. pestis gene, and these alleles were identical or nearly identical to alleles from Y. pseudotuberculosis. Thus, Y. pestis is a clone that evolved from Y. pseudotuberculosis 1,500-20,000 years ago, shortly before the first known pandemics of human plague. Three biovars (Antiqua, Medievalis, and Orientalis) have been distinguished by microbiologists within the Y. pestis clone. These biovars form distinct branches of a phylogenetic tree based on restriction fragment length polymorphisms of the locations of the IS100 insertion element. These data are consistent with previous inferences that Antiqua caused a plague pandemic in the sixth century, Medievalis caused the Black Death and subsequent epidemics during the second pandemic wave, and Orientalis caused the current plague pandemic.
Ligand-Modified Aminobisphosphonate for Linking Proteins to Hydroxyapatite and Bone Surface (2007)

An increase in bone resorption is one of the main symptoms of osteoporosis, a disease that affects more and more individuals every day. Bisphosphonates are known to inhibit bone resorption and thus are being used as a treatment for osteoporosis. Aminobisphosphonates present a functionality that can be easily used for conjugation to other molecules, such as peptides, proteins, and ligands for protein recognition. In this study, an aminobisphosphonate conjugated with biotin was used as a model linker for protein attachment to bone. With this system, the interaction of biotinylated aminobisphosphonate with hydroxyapatite, a major mineral component of bone, was investigated. Quantification of the binding of aminobisphosphonate to hydroxyapatite was performed using a fluorescently labeled antibody for biotin. Additionally, the interaction of the biotinylated aminobisphosphonate with multiple treatments of cortical bone from the midshaft of a cow femur was studied. It was demonstrated that modified aminobisphosphonate reagents can bind hydroxyapatite and bone at high levels, while the biotin functionality is free to be recognized by the fluorescently labeled antibiotin antibody, suggesting that modified aminobisphosphonates could be used to link other peptides or proteins to the bone surface.
Synthesis of nucleoside sulfamates related to nucleocidin (1970)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of nucleoside sulfamates related to nucleocidinDennis A. Shuman, Morris J. Robins, and Roland K. RobinsCite this: J. Am. Chem. Soc. 1970, 92, 11, 3434–3440Publication Date (Print):June 1, 1970Publication History Published online1 May 2002Published inissue 1 June 1970https://pubs.acs.org/doi/10.1021/ja00714a035https://doi.org/10.1021/ja00714a035research-articleACS PublicationsRequest reuse permissionsArticle Views519Altmetric-Citations43LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Proteomic characterization of novel serum amyloid P component variants from human plasma and urine (2004)

Serum amyloid P component (SAP) is a human plasma protein that has been widely studied for its influence on amyloid plaque formation and stabilization. SAP was characterized directly from human plasma and urine samples via novel affinity mass spectrometry-based proteomic technology that is able to readily discriminate between mass-altered protein variants. These analyses were able to identify several variants of SAP that have not been previously reported. These variants include microheterogeneity of the glycan structure, from the loss of one or both terminal sialic acid residues, as well as the loss of the C-terminal valine residue. Moreover, the analysis of urine allowed for the consistent identification of serum amyloid P component as a normal constituent of the urine proteome.
Coating-techniques to improve the hemocompatibility of artificial devices used for extracorporeal circulation (1999)

Above and beyond the long-term applications, routine heart operations have also markedly begun to utilize heparin-coated devices. This trend will assuredly continue in the coming years and is an important step toward higher hemocompatibility of blood-contacting surfaces in the ECC device. Heparin-coatings are merely the beginning of improved hemocompatibility for all materials that come into contact with human blood or tissues. Intelligent materials with almost completely physiological surfaces will be at the surgeon's disposal within the next few years.
Reversible Defects in Natural Killer and Memory Cd8 T Cell Lineages in Interleukin 15–Deficient Mice (2000)

C57BL/6 mice genetically deficient in interleukin 15 (IL-15(-/-) mice) were generated by gene targeting. IL-15(-/-) mice displayed marked reductions in numbers of thymic and peripheral natural killer (NK) T cells, memory phenotype CD8(+) T cells, and distinct subpopulations of intestinal intraepithelial lymphocytes (IELs). The reduction but not absence of these populations in IL-15(-/-) mice likely reflects an important role for IL-15 for expansion and/or survival of these cells. IL-15(-/-) mice lacked NK cells, as assessed by both immunophenotyping and functional criteria, indicating an obligate role for IL-15 in the development and functional maturation of NK cells. Specific defects associated with IL-15 deficiency were reversed by in vivo administration of exogenous IL-15. Despite their immunological defects, IL-15(-/-) mice remained healthy when maintained under specific pathogen-free conditions. However, IL-15(-/-) mice are likely to have compromised host defense responses to various pathogens, as they were unable to mount a protective response to challenge with vaccinia virus. These data reveal critical roles for IL-15 in the development of specific lymphoid lineages. Moreover, the ability to rescue lymphoid defects in IL-15(-/-) mice by IL-15 administration represents a powerful means by which to further elucidate the biological roles of this cytokine.
Efficient Gene Delivery and Targeted Expression to Hepatocytes In Vivo by Improved Lentiviral Vectors (2002)

Safe and efficient genetic modification of liver cells could enable new therapies for a variety of hepatic and systemic diseases. Lentiviral vectors are promising tools for in vivo gene delivery. Previous data suggested that recruitment into the cell cycle was required for transduction of hepatocytes in vivo. We developed an improved vector design that enhanced nuclear translocation in target cells and significantly improved gene transfer performance. Using the new vector and a panel of internal promoters, we showed that rat hepatocytes were transduced ex vivo to high frequency without requirement for proliferation. On intravenous administration of vector into adult severe combined immunodeficient (SCID) mice, we found high levels (up to 30%) of transduction of parenchymal and nonparenchymal cells of the liver, integration of the vector genome in liver DNA and stable expression of the marker green fluorescent protein (GFP)-encoding gene without signs of toxicity. Coadministration of vectors and 5'-bromo-2'-deoxyuridine in vivo proved that cell cycling was not required for efficient transduction of hepatocytes. In addition to the liver, the spleen and the bone marrow were transduced effectively by systemic delivery of vector. GFP expression was observed in all these organs when driven by the cytomegalovirus promoter and by the phosphoglycerate kinase gene promoter. Using the promoter of the albumin gene, we could restrict expression to hepatocytes. By a single vector injection into the bloodstream of SCID mice, we achieved therapeutic-range levels of the human clotting factor IX, stable in the plasma for up to 1 year (the longest time tested), indicating the potential efficacy of improved lentiviral vectors for the gene therapy of hemophilias and other diseases.
Multiplexed protein and gene profiling of circulating tumor cells (CTCs) in metastatic castration-resistant prostate cancer (mCRPC) using automated immunofluorescence and fluorescence in situ hybridization. (2013)

158 Background: Clinically, CTCs are used primarily in longitudinal monitoring of metastatic disease progression. However, the analysis of specific CTC biomarkers has the potential to optimize patient management by identifying those likely to respond to specific targeted agents. Often, mCRPC is driven by dysregulation of the androgen receptor (AR) and phosphatidylinositol 3-kinase/protein kinase B (PI 3 K/AKT) oncogenic pathways such that blockade of one pathway stimulates the other. These functional deficits in the AR and PI3K/AKT pathways are associated with fusion of the TMPRSS2 and ERG genes and with loss of PTEN protein, respectively. Therefore, we sought to characterize CTCs for the simultaneous presence of both these biomarkers using immunofluorescence (IF) and fluorescence in situ hybridization (FISH). Methods: Nucleated peripheral blood cells from mCRPC patients were attached to slides and examined using CTC technology (Epic Sciences). Cytokeratin-positive/CD45-negative cells with an intact nucleus and a malignancy-consistent morphology were identified as CTCs, and their exact positions on the slides were recorded. The slides were then subjected to multiplex Quantum Dot IF and FISH procedures with anti-AR, -ERG, and -PTEN antibodies and 5’ERG, 3’ERG, PTEN, and Cen10 probes, respectively, on an automated slide-staining platform (Ventana Medical Systems, Inc.). The IF and FISH signals were visualized by spectral imaging (Ventana). Results: The automated IF/FISH staining procedure facilitated multiplex characterization of individual CTCs from patient samples for the protein biomarker targets AR, ERG, and PTEN and the genomic biomarker targets 5’ERG, 3’ERG, PTEN, and Cen10. Conclusions: This method for high-sensitivity, multiplex molecular characterization of critical CTC biomarkers in mCRPC patients might aid oncologists in identifying and stratifying those patients likely to respond to combination therapy with targeted PI 3 K/AKT inhibitors and anti-androgens/Cyp17 inhibitors. Patient trials examining the clinical utility of this assay in mCRPC are currently underway.
Non-viral Delivery of Nucleic Acids: Insight Into Mechanisms of Overcoming Intracellular Barriers (2018)

Delivery of genes, including plasmid DNAs, short interfering RNAs (siRNAs), and messenger RNAs (mRNAs), using artificial non-viral nanotherapeutics is a promising approach in cancer gene therapy. However, multiple physiological barriers upon systemic administration remain a key challenge in clinical translation of anti-cancer gene therapeutics. Besides extracellular barriers including sequestration of gene delivery nanoparticles from the bloodstream by resident organ-specific macrophages, and their poor extravasation and tissue penetration in tumors, overcoming intracellular barriers is also necessary for successful delivery of nucleic acids. Whereas for RNA delivery the endosomal barrier holds a key importance, transfer of DNA cargo additionally requires translocation into the nucleus. Better understanding of crossing membrane barriers by nucleic acid nanoformulations is essential to the improvement of current non-viral carriers. This review aims to summarize relevant literature on intracellular trafficking of non-viral nanoparticles and determine key factors toward surmounting intracellular barriers. Moreover, recent data allowed us to propose new interpretations of current hypotheses of endosomal escape mechanisms of nucleic acid nanoformulations.
A Planar Labyrinth Micromixer (2010)

Rapid mixing of two fluids in microchannels has posed an important challenge to the development of many integrated lab-on-a-chip systems. In this paper, we present a planar labyrinth micromixer (PLM) to achieve rapid and passive mixing by taking advantage of a synergistic combination of the Dean vortices in curved channels, a series of perturbation to the fluids from the sharp turns, and an expansion and contraction of the flow field via a circular chamber. The PLM is constructed in a single soft lithography step and the labyrinth has a footprint of 7.32 mm × 7.32 mm. Experiments using fluorescein isothiocyanate solutions and deionized water demonstrate that the design achieves fast and uniform mixing within 9.8 s to 32 ms for Reynolds numbers between 2.5 and 30. Compared to the mixing in the prevalent serpentine design, our design results in 38% and 79% improvements on the mixing efficiency at Re = 5 and Re = 30 respectively. An inverse relationship between mixing length and mass transfer Pe´clet number (Pe) is observed, which is superior to the logarithmic dependence of mixing length on Pe in chaotic mixers. Having a simple planar structure, the PLM can be easily integrated into lab-on-a-chip devices where passive mixing is needed.
Laminar optical tomography: high-resolution 3D functional imaging of superficial tissues (2006)

Laminar Optical Tomography (LOT) is a new medical imaging modality for high-resolution, depth-resolved, functional imaging of superficial tissue such as rodent cortex, skin and the retina. LOT uses visible laser light to image to depths of >2mm (far deeper than microscopy) and is highly sensitive to absorption and fluorescence contrast, enabling spectroscopic functional information such as hemoglobin oxygenation to be imaged with 100-200 micron resolution. LOT has been used to image the hemodynamic response to stimulus in the somatosensory cortex of rats. The resulting three-dimensional (3D) images through the depth of the cortex can be used to delineate the arterial, capillary and venous responses, revealing new information about the intricacies of the oxygenation and blood flow dynamics related to neuronal activation. Additional applications of LOT are being explored, including the integration of 3D Voltage Sensitive Dye fluorescence imaging. LOT imaging uses a system similar to a confocal microscope, quickly scanning a focused beam of light over the surface of the tissue (~8Hz frame rate). Light is detected from both the focus of the scanning beam, and also at increasing distances from the beam's focus. This scattered light has penetrated more deeply into the tissue, and allows features at different depths to be distinguished. An algorithm that includes photon migration modeling of light scattering converts the raw data into 3D images. The motivation for functional optical imaging will be outlined, the basic principles of LOT imaging will be described, and the latest in-vivo results will be presented.
Decreased human immunodeficiency virus type 1 plasma viremia during antiretroviral therapy reflects downregulation of viral replication in lymphoid tissue. (1995)

Although several immunologic and virologic markers measured in peripheral blood are useful for predicting accelerated progression of human immunodeficiency virus (HIV) disease, their validity for evaluating the response to antiretroviral therapy and their ability to accurately reflect changes in lymphoid organs remain unclear. In the present study, changes in certain virologic markers have been analyzed in peripheral blood and lymphoid tissue during antiretroviral therapy. Sixteen HIV-infected individuals who were receiving antiretroviral therapy with zidovudine for > or = 6 months were randomly assigned either to continue on zidovudine alone or to add didanosine for 8 weeks. Lymph node biopsies were performed at baseline and after 8 weeks. Viral burden (i.e., HIV DNA copies per 10(6) mononuclear cells) and virus replication in mononuclear cells isolated from peripheral blood and lymph node and plasma viremia were determined by semiquantitative polymerase chain reaction assays. Virologic and immunologic markers remained unchanged in peripheral blood and lymph node of patients who continued on zidovudine alone. In contrast, a decrease in virus replication in lymph nodes was observed in four of six patients who added didanosine to their regimen, and this was associated with a decrease in plasma viremia. These results indicate that decreases in plasma viremia detected during antiretroviral therapy reflect downregulation of virus replication in lymphoid tissue.
What is acceptable quality in the application of digital watermarking: trade-offs of security, robustness and quality (2005)

Quality is subjective, Quality can be objectified by the industry standards process represented by such consumer items as compact disc ("CD") and digital versatile disc ("DVD"). What is lacking is a means for not only associating the creation of valued intangible assets and extensions of recognition but establishing responsibility for copies that may be digitized or pass through a digital domain. Digital watermarking exists at a convergence point between piracy and privacy. Watermarks serve as a receipt for information commerce. There is not likely to be a single digital watermark encoding scheme that best handles the trade-offs between security, robustness, and quality but several architectures to handle various concerns. The most commercially useful watermarking schemes are keybased, combining cryptographic features with models of perception. Most importantly, in audio watermarking there currently exists mature technologies which have been proven to be statistically inaudible. In this paper, a description of several of the decoding system applications, and why watermarks are a necessary feature of any workable market for the commercial exchange of content is highlighted.
Array‐CGH analysis of cell‐free fetal DNA in 10 mL of amniotic fluid supernatant (2007)

CffDNA extracted from 10 mL AF supernatant can be analyzed using array-CGH to correctly identify human chromosome abnormalities. This technology allows for rapid screening of AF samples for whole chromosomal changes by using routinely discarded supernatant, and may augment standard prenatal karyotyping techniques by providing additional molecular information.
From few to many: illumination cone models for face recognition under variable lighting and pose (2001)

We present a generative appearance-based method for recognizing human faces under variation in lighting and viewpoint. Our method exploits the fact that the set of images of an object in fixed pose, but under all possible illumination conditions, is a convex cone in the space of images. Using a small number of training images of each face taken with different lighting directions, the shape and albedo of the face can be reconstructed. In turn, this reconstruction serves as a generative model that can be used to render (or synthesize) images of the face under novel poses and illumination conditions. The pose space is then sampled and, for each pose, the corresponding illumination cone is approximated by a low-dimensional linear subspace whose basis vectors are estimated using the generative model. Our recognition algorithm assigns to a test image the identity of the closest approximated illumination cone. Test results show that the method performs almost without error, except on the most extreme lighting directions.
Protein purification techniques : a practical approach (2001)

Purification strategy Getting started Analysis of purity Clarification techniques Cell disintegration and extraction techniques Concentration of the extract Separation on the basis of chemistry Chromatography on the basis of size Purification by exploitation of activity Scale up