gebhart/patrepeval huggingface dataset:
Phorbol ester-mediated downregulation of tropoelastin expression is controlled by a posttranscriptional mechanism (1992)

Expression of tropoelastin, the principal precursor of elastic fibers, is tissue-specific and is limited to a brief developmental period. Little is known, however, about the mechanisms that regulate the tissue- and temporal-specific expression of elastogenesis. The tropoelastin promoter contains putative phorbol ester responsive elements, or AP-1 binding sites, but the functional significance of these sequences is unknown. To test if tropoelastin expression is influenced by phorbol esters, we exposed elastogenic fetal bovine chondrocytes to 10(-7) M 12-O-tetradecanoylphorbol 13-acetate (TPA). Tropoelastin mRNA levels decreased greater than 10-fold in response to TPA, and this downregulation was paralleled by a decline in the secretion of tropoelastin protein into the culture medium. As determined by nuclear-runoff assay and transient transfection with a human gene promoter-CAT construct, tropoelastin transcription was unaffected after exposure to TPA. As indicated by actinomycin D experiments, the half-life of tropoelastin mRNA in control cells was about 20 h, but exposure to TPA resulted in an accelerated decay of the tropoelastin transcript (t1/2 = 2.2 h). These data indicate that downregulation of tropoelastin expression was controlled by a posttranscriptional mechanism and that the AP-1 elements in the bovine tropoelastin promoter may not be involved in regulation of production.
Self-organized vascular networks from human pluripotent stem cells in a synthetic matrix (2013)

The success of tissue regenerative therapies is contingent on functional and multicellular vasculature within the redeveloping tissue. Although endothelial cells (ECs), which compose the vasculature's inner lining, are intrinsically able to form nascent networks, these structures regress without the recruitment of pericytes, supporting cells that surround microvessel endothelium. Reconstruction of typical in vivo microvascular architecture traditionally has been done using distinct cell sources of ECs and pericytes within naturally occurring matrices; however, the limited sources of clinically relevant human cells and the inherent chemical and physical properties of natural materials hamper the translational potential of these approaches. Here we derived a bicellular vascular population from human pluripotent stem cells (hPSCs) that undergoes morphogenesis and assembly in a synthetic matrix. We found that hPSCs can be induced to codifferentiate into early vascular cells (EVCs) in a clinically relevant strategy amenable to multiple hPSC lines. These EVCs can mature into ECs and pericytes, and can self-organize to form microvascular networks in an engineered matrix. These engineered human vascular networks survive implantation, integrate with the host vasculature, and establish blood flow. This integrated approach, in which a derived bicellular population is exploited for its intrinsic self-assembly capability to create microvasculature in a deliverable matrix, has vast ramifications for vascular construction and regenerative medicine.
Glial Progenitors in the CNS and Possible Lineage Relationships Among Them (2004)

Summry— Glial cells are derived from stem cells that mature through specific stages of development to generate fully differentiated astrocytes and oligodendrocytes. Several types of intermediate precursors have been described and in some cases lineage relationships identified although this remains a subject of controversy. We review recent findings and discuss some possibilities. Motoneuron‐oligodendrocyte precursors (MNOPs), white matter progenitor cells (WMPCs), polydendrocytes, glial restricted precursors (GRPs), astrocyte precursor cells (APCs), and oligodendroblasts are likely all derived from earlier appearing stem cells but segregate at different stages in development. Some of these precursors persist in the adult, and it is these glial progenitors rather than stem cells that respond after injury and participate in the repair process. Although which specific glial progenitor responds remains unclear, the availability of new markers will likely resolve this issue. We believe that the development of consensus sets of markers and an improvement in our ability to define stages of glial maturation will lead to a clearer appreciation of the importance of glia in the etiopathology of disease.
Biofilm Formation and Interaction with the Surfaces of Gallstones by Salmonella spp (2002)

Salmonellae can exist in an asymptomatic carrier state in the human gallbladder. Individuals with gallstones are more likely to become typhoid carriers, and antibiotic treatments are often ineffectual against Salmonella enterica serovar Typhi in carriers with gallstones. Therefore, we hypothesized that Salmonella spp. form biofilms on the surfaces of gallstones, where the bacteria are protected from high concentrations of bile and antibiotics. A number of methods were utilized to examine biofilm formation on human gallstones and glass coverslips in vitro, including confocal, light, and scanning electron microscopy. In our assays, salmonellae formed full biofilms on the surfaces of gallstones within 14 days and appeared to excrete an exopolysaccharide layer that bound them to the surfaces and to other bacteria. Efficient biofilm formation on gallstones was dependent upon the presence of bile, as a biofilm did not form on gallstones within 14 days in Luria-Bertani broth alone. The biofilms formed by a Salmonella enterica serovar Typhi Vi antigen mutant, as well as strains with mutations in genes that eliminate production of four different fimbriae, were indistinguishable from the biofilms formed by the parents. Mutants with an incomplete O-antigen, mutants that were nonmotile, and mutants deficient in quorum sensing were unable to develop complete biofilms. In addition, there appeared to be selectivity in salmonella binding to the gallstone surface that did not depend on the topology or surface architecture. These studies should aid in the understanding of the Salmonella carrier state, an important but underresearched area of typhoid fever pathogenesis. If the basis of carrier development can be understood, it may be possible to identify effective strategies to prevent or treat this chronic infection.
A fluorescence resonance energy transfer-derived structure of a quantum dot-protein bioconjugate nanoassembly (2004)

The first generation of luminescent semiconductor quantum dot (QD)-based hybrid inorganic biomaterials and sensors is now being developed. It is crucial to understand how bioreceptors, especially proteins, interact with these inorganic nanomaterials. As a model system for study, we use Rhodamine red-labeled engineered variants of Escherichia coli maltose-binding protein (MBP) coordinated to the surface of 555-nm emitting CdSe-ZnS core-shell QDs. Fluorescence resonance energy transfer studies were performed to determine the distance from each of six unique MBP-Rhodamine red dye-acceptor locations to the center of the energy-donating QD. In a strategy analogous to a nanoscale global positioning system determination, we use the intraassembly distances determined from the fluorescence resonance energy transfer measurements, the MBP crystallographic coordinates, and a least-squares approach to determine the orientation of the MBP relative to the QD surface. Results indicate that MBP has a preferred orientation on the QD surface. The refined model is in agreement with other evidence, which indicates coordination of the protein to the QD occurs by means of its C-terminal pentahistidine tail, and the size of the QD estimated from the model is in good agreement with physical measurements of QD size. The approach detailed here may be useful in determining the orientation of proteins in other hybrid protein-nanoparticle materials. To our knowledge, this is the first structural model of a hybrid luminescent QD-protein receptor assembly elucidated by using spectroscopic measurements in conjunction with crystallographic and other data.
Metal ion promoted phosphate ester hydrolysis. Intramolecular attack of coordinated hydroxide ion (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMetal ion promoted phosphate ester hydrolysis. Intramolecular attack of coordinated hydroxide ionPhilip Hendry and Alan M. SargesonCite this: J. Am. Chem. Soc. 1989, 111, 7, 2521–2527Publication Date (Print):March 1, 1989Publication History Published online1 May 2002Published inissue 1 March 1989https://pubs.acs.org/doi/10.1021/ja00189a025https://doi.org/10.1021/ja00189a025research-articleACS PublicationsRequest reuse permissionsArticle Views781Altmetric-Citations94LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
An update on the recent advances in antifibrotic therapy (2018)

Chronic injury to the liver, such as viral hepatitis, alcoholism, non-alcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH), promotes extracellular matrix deposition and organ scarring, termed hepatic fibrosis. Fibrosis might progress to cirrhosis and predisposes to hepatocellular carcinoma (HCC), but is also associated with extrahepatic morbidity and mortality in NAFLD/NASH. The improved understanding of pathogenic mechanisms underlying chronic inflammation and fibrogenesis in the liver prompted recent advances in antifibrotic therapies. Areas covered: We review recent advances in antifibrotic therapy, of which most are currently tested in clinical trials for NAFLD or NASH. This explains the manifold metabolic pathways as antifibrotic targets, including farnesoid X receptor (FXR) agonism (obeticholic acid, nonsteroidal FXR agonists), acetyl-CoA carboxylase inhibition, peroxisome proliferator-activator receptor agonism (elafibranor, lanifibranor, saroglitazar), and fibroblast growth factor (FGF)-21 or FGF-19 activation. Other antifibrotic drug candidates target cell death or inflammation, such as caspase (emricasan) or ASK1 inhibitors (selonsertib), galectin-3 inhibitors and reducing inflammatory macrophage recruitment by blocking chemokine receptors CCR2/CCR5 (cenicriviroc). Expert commentary: The tremendous advances in translational and clinical research fuels the hope for efficacious antifibrotic therapies within the next 5 years. Very likely, a combination of etiology-specific, metabolic, anti-inflammatory, and direct antifibrotic interventions will be most effective.
Optical properties of multicellular tumour spheroids (1996)

Multicellular tumour spheroids grown in vitro have been widely used in cancer research as an experimental preparation with many of the characteristics of tumours. They provide a model system for understanding the optical behaviour of tumour tissue, which is of interest in novel diagnostic and therapeutic procedures. Optical measurements on fresh spheroids in the wavelength range of 600-1000 nm yielded scattering coefficients, absorption coefficients and g values (mean cosine of scatter) of 160-90 mm-1, 0.1-0.4 mm-1 and 0.99, respectively. Following fixation, considerably higher values of scattering and absorption coefficients were seen. The values are compared with those reported elsewhere for excised tumour tissue and interpretations of the optical behaviour are suggested.
DRAW: A Recurrent Neural Network For Image Generation (2015)

This paper introduces the Deep Recurrent Attentive Writer (DRAW) neural network architecture for image generation. DRAW networks combine a novel spatial attention mechanism that mimics the foveation of the human eye, with a sequential variational auto-encoding framework that allows for the iterative construction of complex images. The system substantially improves on the state of the art for generative models on MNIST, and, when trained on the Street View House Numbers dataset, it generates images that cannot be distinguished from real data with the naked eye.
Submucosal Bladder Neck Injection of Bovine Dermal Collagen for Stress Urinary Incontinence in the Pediatric Population (1996)

The surgical management of stress urinary incontinence in the pediatric population includes various surgical techniques of which the simplest is outpatient transurethral or periurethral injection of a bulking agent. Currently purified bovine dermal collagen cross-linked with glutaraldehyde (Contigen) is the only Food and Drug Administration approved bulking agent available. Patients with stable detrusor function are ideal candidates. We review our initial experience with children.Between January 1994 and June 1995, 23 boys and 9 girls 4 to 17 years old (mean age 9) consecutively underwent submucosal bladder neck injection with cross-linked bovine dermal collagen. Incontinence was secondary to spinal dysraphism in 24 patients, complete epispadias in 4, classic bladder exstrophy in 3 and neurogenic bladder secondary to a sacral teratoma in 1. Preoperative video urodynamics documented intrinsic sphincteric deficiency in all patients with leak point pressure of 15 to 60 cm. water (mean 37). Injection volumes ranged from 2.5 to 17 cc (mean 10). Continence results were defined as dry-requiring no protection while on a 4-hour clean intermittent catheterization program, good-improved but requiring 1 to 5 pads daily and failure-no postoperative improvement or still requiring diapers.Of the children with neurogenic bladder 20% became dry following the first injection and an additional 28% had a good result. Furthermore, of the 6 children with exstrophy or epispadias who underwent a Young-Dees-Leadbetter procedure 50% were dry and 17% had a good result after the first injection. Complications were limited to a febrile urinary tract infection associated with urinary retention in 1 patient and transiently worse continence in 2.Despite the limited success rate, we believe that transurethral collagen injection therapy has a viable role in the treatment of intrinsic sphincteric deficiency in select pediatric patients, particularly since the procedure has low morbidity and can be performed on an outpatient basis. Preoperative counseling should be given with realistic expectations.
Rapid engineering of bacterial artificial chromosomes using oligonucleotides (2000)

A rapid method obviating the use of selectable markers to genetically manipulate large DNA inserts cloned into bacterial artificial chromosomes is described. Mutations such as single-base changes, deletions, and insertions can be recombined into a BAC by using synthetic single-stranded oligonucleotides as targeting vectors. The oligonucleotides include the mutated sequence flanked by short homology arms of 35-70 bases on either side that recombine with the BAC. In the absence of any selectable marker, modified BACs are identified by specific PCR amplification of the mutated BAC from cultures of pooled bacterial cells. Each pool represents about 10 electroporated cells from the original recombination mixture. Subsequently, individual clones containing the desired alteration are identified from the positive pools. Using this BAC modification method, we have observed a frequency of one recombinant clone per 90-260 electroporated cells. The combination of high targeting frequency and the sensitive yet selective PCR-based screening method makes BAC manipulation using oligonucleotides both rapid and simple.
Cytokine Maturation Followed by CD40L mRNA Electroporation Results in a Clinically Relevant Dendritic Cell Product Capable of Inducing a Potent Proinflammatory CTL Response (2008)

Dendritic cells (DC) for the immunotherapy of cancer and infectious disease require the appropriate maturation and activation signals to effectively present antigen to drive a proinflammatory response. Here we present a comparison of 4 different maturation protocols for antigen-encoded mRNA electroporated DC. Two protocols rely on cytokine-induced maturation given either preelectroporation or postelectroporation. In addition to the cytokine treatment, 2 further maturation protocols use coelectroporation of CD40L mRNA, with antigen-encoding RNA, to deliver CD40 signals. There were no significant differences in expression of costimulatory molecules such as CD80, CD83, and CD86 or the levels of expression of major histocompatibility complexes. However, results indicate that delivery of an inflammatory signal that includes interferon-gamma before the CD40 signal results in high levels of expression of interleukin-12 that was not seen in the absence of CD40L mRNA. All 4 preparations could induce expansion of primary MART-1-specific CD8+ T cells from healthy donors in vitro, but only the 2 processes receiving CD40L could induce interferon-gamma expression by those responder cells. Only DC electroporated with CD40L RNA after delivery of the inflammatory signal (PME-CD40L DC), could drive the long-term expansion of MART-1-reactive cells that displayed a CD28+/CD45RA- effector/memory phenotype with strong cytolytic activity.
HTLV-III large envelope protein (gp120) suppresses PHA-induced lymphocyte blastogenesis. (1987)

The addition of inactivated preparations of purified human T cell lymphotropic virus (HTLV-III) was found to inhibit normal human lymphocyte phytohemagglutinin (PHA)-induced blastogenesis but had no effect on concanavalin A (Con A), pokeweek mitogen, or allogeneic stimulation. The inhibition was concentration-dependent and also dependent on adding the virus preparation before or at the same time as PHA. The CD4 molecule is the receptor for HTLV-III binding. Immunopurified large envelope protein (gp120) from HTLV-III was found to bind to the CD4 molecule and also inhibited PHA-induced lymphocyte blastogenesis. These results suggest that the gp120 viral protein may alter immune function by binding to the CD4 molecule, which in turn serves as an "off" signal to lymphocyte response to PHA stimulation. Alternatively, by binding to the CD4 molecule, gp120 may interfere with the interaction of this molecule with class II histocompatibility antigens on accessory cells, thus selectively suppressing PHA response.
Leaf optical properties in higher plants: linking spectral characteristics to stress and chlorophyll concentration (2001)

A number of studies have linked responses in leaf spectral reflectance, transmittance, or absorptance to physiological stress. A variety of stressors including dehydration, flooding, freezing, ozone, herbicides, competition, disease, insects, and deficiencies in ectomycorrhizal development and N fertilization have been imposed on species ranging from grasses to conifers and deciduous trees. In all cases, the maximum difference in reflectance within the 400-850 nm wavelength range between control and stressed states occurred as a reflectance increase at wavelengths near 700 nm. In studies that included transmittance and absorptance as well as reflectance, maximum differences occurred as increases and decreases, respectively, near 700 nm. This common optical response to stress could be simulated closely by varying the chlorophyll concentration of model leaves (fiberglass filter pads) and by the natural variability in leaf chlorophyll concentrations in senescent leaves of five species. The optical response to stress near 700 nm, as well as corresponding changes in reflectance that occur in the green-yellow spectrum, can be explained by the general tendency of stress to reduce leaf chlorophyll concentration.
B4GALNT2 and xenotransplantation: A newly appreciated xenogeneic antigen (2018)

Analysis of non-Gal antibody induced after pig-to-baboon cardiac xenotransplantation identified the glycan produced by porcine beta-1,4-N-acetyl-galactosaminyltransferase 2 (B4GALNT2) as an immunogenic xenotransplantation antigen. The porcine B4GALNT2 enzyme is homologous to the human enzyme, which synthesizes the human SDa blood group antigen. Most humans produce low levels of anti-SDa IgM which polyagglutinates red blood cells from rare individuals with high levels of SDa expression. The SDa glycan is also present on GM2 gangliosides. Clinical GM2 vaccination studies for melanoma patients suggest that a human antibody response to SDa can be induced. Expression of porcine B4GALNT2 in human HEK293 cells results in increased binding of anti-SDa antibody and increased binding of Dolichos biflorus agglutinin (DBA), a lectin commonly used to detect SDa. In pigs, B4GALNT2 is expressed by vascular endothelial cells and endothelial cells from a wide variety of pig backgrounds stain with DBA, suggesting that porcine vascular expression of B4GALNT2 is not polymorphic. Mutations in B4GALNT2 have been engineered in mice and pigs. In both species, the B4GALNT2-KO animals are apparently normal and no longer show evidence of SDa antigen expression. Pig tissues with a mutation in B4GALNT2, added to a background of alpha-1,3-galactosyltransferase deficient (GGTA1-KO) and cytidine monophosphate-N-acetylneuraminic acid hydroxylase deficient (CMAH-KO), show reduced antibody binding, confirming the presence of B4GALNT2-dependent antibodies in both humans and non-human primates. Preclinical xenotransplantation using B4GALNT2-deficient donors has recently been reported. Elimination of this source of immunogenic pig antigen should minimize acute injury by preformed anti-pig antibody and eliminate an induced clinical immune response to this newly appreciated xenotransplantation antigen.
Adaptive strain estimation using retrospective processing [medical US elasticity imaging] (1999)

Because errors in displacement and strain estimates depend on the magnitude of the induced strain, the strain signal-to-noise ratio (SNR) will be a function of the applied deformation. If deformation is applied at the body surface, it is difficult during data acquisition to select a single surface displacement providing the highest strain SNR throughout the image. By applying continuous deformation and capturing data in real-time, the surface displacement providing the highest strain SNR can be selected retrospectively. A method to adaptively optimize strain SNR over the image plane using retrospective processing is presented and demonstrated with experimental results.