gebhart/patrepeval huggingface dataset:
Conditional Expression of a Dominant-Negative c-Myb in Vascular Smooth Muscle Cells Inhibits Arterial Remodeling After Injury (2003)

Inhibiting activity of the c-Myb transcription factor attenuates G1 to S phase cell cycle transitions in vascular smooth muscle cells (SMCs) in vitro. To determine the effects of arterial SMC-specific expression of a dominant-negative c-Myb molecule (Myb-Engrailed) on vascular remodeling in vivo, we performed carotid artery wire-denudation in 2 independent lines of binary transgenic mice with SM22alpha promoter-defined Doxycycline-suppressible expression of Myb-Engrailed. Adult mice with arterial SMC-specific expression of Myb-Engrailed were overtly normal in appearance and did not display any changes in cardiovascular structure or physiology. However, bromodeoxyuridine-defined arterial SMC proliferation, neointima formation, medial hyperplasia, and arterial remodeling were markedly decreased in mice expressing arterial SMC-restricted Myb-Engrailed after arterial injury. These data suggest that c-Myb activity in arterial SMCs is not essential for arterial structure or function during development, but is involved in the proliferation of arterial SMCs as occurs in vascular pathology, and that the expression of a dominant-negative c-Myb can dramatically reduce adverse arterial remodeling in an in vivo model of restenosis. As such, this model represents a novel tissue-specific strategy for the potential gene therapy of diseases characterized by arterial SMC proliferation.
Positive selection of hematopoietic CD34+ stem cells provides 'indirect purging' of CD34- lymphoid cells and the purging efficiency is increased by anti-CD2 and anti-CD30 immunotoxins. (1994)

Human CD34+ hematopoietic cells were purified using the avidin-biotin immunoabsorption technique. The selected population showed 78.6 +/- 3% CD34+ cells and the overall recovery of CD34+ cells, CFU-GM and BFU-E from the starting population was 34 +/- 5%, 71 +/- 4% and 67 +/- 2%, respectively. Hematopoietic progenitor cell purification also resulted in 3 log of normal T cell depletion from the bone marrow (BM) by immunofluorescence analysis. Moreover, when unseparated BM cells were mixed with the CD34- lymphoma cell lines D430B and Raji, the removal of greater than 3 log of tumor cells from the enriched CD34+ cell fraction was demonstrated. To increase the neoplastic cell purging, several immunotoxins (IT) containing the ribosome-inactivating protein (RIP) saporin and directed toward the lymphoid-associated antigens CD30 and CD2 were prepared. Our experiments showed only a minimal toxicity of the immunoconjugates on colony-forming cells (CFC) derived from purified CD34+ cells. Conversely, all the ITs were very effective in inhibiting protein synthesis and growth of normal and neoplastic lymphoid cells. Further experiments demonstrated that the sequential combination of CD34+ cells purification and IT treatment resulted in 5 or more log of tumor cell purging with no additional loss of BM progenitor cells.
Travel in immersive virtual environments: an evaluation of viewpoint motion control techniques (2002)

Presents a categorization of techniques for first-person motion control, or travel, through immersive virtual environments, as well as a framework for evaluating the quality of different techniques for specific virtual environment tasks. We conduct three quantitative experiments within this framework: a comparison of different techniques for moving directly to a target object varying in size and distance, a comparison of different techniques for moving relative to a reference object, and a comparison of different motion techniques and their resulting sense of "disorientation" in the user. Results indicate that "pointing" techniques are advantageous relative to "gaze-directed" steering techniques for a relative motion task, and that motion techniques which instantly teleport users to new locations are correlated with increased user disorientation.
Norovirus–host interaction: implications for disease control and prevention (2007)

Noroviruses (NVs) are a major cause of acute gastroenteritis epidemics in both developing and developed countries and affect people of all ages. Three main human histo-blood group antigens (HBGAs) - the ABO, Lewis and secretor families - are involved in NV recognition and eight strain-specific receptor-binding patterns in two major binding groups have been described. The receptor-binding interface is located at the outermost surface of the P domain of the viral capsid. Each interface contains two major binding sites and each site interacts with a carbohydrate side-chain of the HBGAs via multiple hydrogen bonds. Soluble HBGAs in human milk are able to block binding of NV to HBGA receptors, suggesting a potential decoy receptor for the protection of infants from NV infection. Phylogenetic analysis has revealed limited genetic relatedness among NVs with similar receptor-binding patterns. This review summarises and discusses recent advances and highlights implications for future studies in the control and prevention of NV gastroenteritis.
Volumetric capillary cytometry: A new method for absolute cell enumeration (1996)

This article describes a novel cytometry system that is capable of imaging, identifying, and counting populations of fluorescently labeled cells within a precisely known volume of unlysed whole blood contained in a precision capillary. The whole blood is reacted with dye-labeled antibodies directed at cell surface antigens. A red excitation source (helium-neon laser) is used to minimize auto-fluorescence and interference by blood components. A two-color fluorescence detection system is described, using the dyes Cy5 and Cy5.5, allowing the simultaneous detection and quantitation of two different types of surface antigens. Image processing techniques are used to identify cellular events in the image and to quantitate the fluorescent intensities in both color planes. The utility of this technique is demonstrated by performing absolute CD3+/CD4+ lymphocyte counts in whole blood, with minimal sample preparation, and with the blood sample completely contained in a disposable cartridge. A correlation study comparing this technique to flow cytometry gives a correlation coefficient of 0.98. In addition, the ability of this system to monitor reaction kinetics is demonstrated with a measurement of the rate of association of the anti-CD4 antibody onto the surface of CD4+ lymphocytes.
Knowledge-based augmented reality (1993)

article Free Access Share on Knowledge-based augmented reality Authors: Steven Feiner Columbia Univ., New York, NY Columbia Univ., New York, NYView Profile , Blair Macintyre Columbia Univ., New York, NY Columbia Univ., New York, NYView Profile , Dorée Seligmann AT&T Bell Labs, Holmdel, NJ AT&T Bell Labs, Holmdel, NJView Profile Authors Info & Claims Communications of the ACMVolume 36Issue 7July 1993pp 53–62https://doi.org/10.1145/159544.159587Published:01 July 1993Publication History 624citation10,490DownloadsMetricsTotal Citations624Total Downloads10,490Last 12 Months588Last 6 weeks55 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Inhibition of JAK kinase activity enhances Fas-mediated apoptosis but reduces cytotoxic activity of topoisomerase II inhibitors in U266 myeloma cells. (2001)

Our previous work demonstrated that the Janus kinase (JAK)-Stat3 pathway regulates expression of Bcl-x(L) in the U266 human multiple myeloma cell line and prevents Fas-mediated apoptosis. Inhibition of this pathway by the JAK selective kinase inhibitor AG490 or dominant-negative Stat3 protein results in down-regulation of Bcl-x(L) expression and enhanced sensitivity to Fas-mediated apoptosis. Because Bcl-x(L) has also been implicated in resistance to chemotherapeutic drugs, we investigated whether inhibition of the JAK-Stat3 pathway and subsequent reduction in Bcl-x(L) expression would also enhance cytotoxic drug activity. Contrary to this prediction, pretreatment of U266 myeloma cells with AG490, followed by exposure to topoisomerase II- inhibiting agents, antagonized drug-induced apoptosis. This effect correlated with reduced cyclin D1 expression and cell cycle arrest. The cell cycle arrest following AG490 pretreatment further correlated with reduced mitoxantrone-induced DNA double-strand breaks and reduced cell death, findings consistent with the critical requirement of DNA damage for drug cytotoxicity. These studies demonstrate that inhibition of the JAK-Stat3 pathway can result in paradoxical effects relative to cytotoxic drug response. These paradoxical responses may be explained by the findings that JAK-Stat3 signaling regulates the expression of multiple genes involved in controlling cell proliferation and apoptosis. Thus, understanding the cellular context of inhibiting signal transduction pathways is essential for the design of novel combination therapies for cancer.
Novel α-Amino-3-hydroxy-5-methylisoxazole-4-propionate Receptor Antagonists:  Synthesis and Structure−Activity Relationships of 6-(1H-Imidazol-1-yl)- 7-nitro-2,3(1H,4H)-pyrido[2,3-b]pyrazinedione and Related Compounds (1996)

We have synthesized and evaluated azaquinoxalinediones 3a-c for their activity in inhibiting [3H]AMPA binding from rat whole brain. It was found that the azaquinoxalinedione nucleus functions as a bioisostere for quinoxalinedione in AMPA receptor binding. The detailed structure-activity relationships of 6- and/or 7-substituted 2,3(1H,4H)-pyrido[2,3-b]pyrazinedione derivatives 4, 7-1-, 13, 15 and 16 showed some differences in comparison with those of the corresponding substituted quinoxalinediones, including 6-(1H-imidazol-1-yl)-7-nitro-2,3-(1H,4H)-quinoxalinedione (1) (YM90K). The X-ray study exhibited that conformation of the 7-nitro group of 1.HCl was nearly coplanar with the quinoxaline ring, whereas the 6-imidazol-1-yl group was rotated with respect to the aromatic ring. From the glycine site on NMDA receptor binding study, it is indicated that bulkiness of 6-substituents on pyridopyrazinediones may be responsible for the selectivity against the glycine site. Among the series of azaquinoxalinediones, 6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-pyrido[2,3-b]pyrazinedione (8c) exhibited a combination of the best affinity to AMPA receptors with a Ki value of 0.14 microM and selectivity against the glycine site (no affinity at 10 microM). In vivo, 8c also protected against sound-induced seizure in DBA/2 mice (minimum effective dose, 10 mg/kg ip).
Improved Production of Gutted Adenovirus in Cells Expressing Adenovirus Preterminal Protein and DNA Polymerase (1999)

Production of gutted, or helper-dependent, adenovirus vectors by current methods is inefficient. Typically, a plasmid form of the gutted genome is transfected with helper viral DNA into 293 cells; the resulting lysate is serially passaged to increase the titer of gutted virions. Inefficient production of gutted virus particles after cotransfection is likely due to suboptimal association of replication factors with the abnormal origins found in these plasmid substrates. To test this hypothesis, we explored whether gutted virus production would be facilitated by transfection into cells expressing various viral replication factors. We observed that C7 cells, coexpressing adenoviral DNA polymerase and preterminal protein, converted plasmid DNA into replicating virus approximately 50 times more efficiently than did 293 cells. This property of C7 cells can be used to greatly increase the efficiency of gutted virus production after cotransfection of gutted and helper viral DNA. These cells should also be useful for generation of recombinant adenovirus from any plasmid-based precursor.
Targeted Correction of Single-Base-Pair Mutations with Adeno-Associated Virus Vectors under Nonselective Conditions (2004)

Recombinant adeno-associated virus (rAAV) vectors possess the unique ability to introduce genetic alterations at sites of homology in genomic DNA through a mechanism thought to predominantly involve homologous recombination. We have investigated the efficiency of this approach using a mutant enhanced green fluorescent protein (eGFP) fluorescence recovery assay that facilitates detection of gene correction events in living cells under nonselective conditions. Our data demonstrate that rAAV infection can correct a mutant eGFP transgene at an efficiency of 0.1% in 293 cells, as determined by fluorescence-activated cell-sorting analysis. Gene repair was also confirmed using clonal expansion of GFP-positive cells and sequencing of the eGFP transgene. These results support previous findings demonstrating the efficacy of rAAV for gene targeting. In an effort to improve gene-targeting efficiencies, we evaluated several agents known to increase rAAV transduction (i.e., expression of an expressed gene), including genotoxic stress and proteasome inhibitors, but observed no correlation between the level of gene repair and rAAV transduction. Interestingly, however, our results demonstrated that enrichment of G(1)/S-phase cells in the target population through the addition of thymidine moderately (approximately 2-fold) increased gene correction compared to cells in other cell cycle phases, including G(0)/G1, G(1), and G(2)/M. These results suggest that the S phase of the cell cycle may more efficiently facilitate gene repair by rAAV. Transgenic mice expressing the mutant GFP were used to evaluate rAAV targeting efficiencies in primary fetal fibroblast and tibialis muscles. However, targeting efficiencies in primary mouse fetal fibroblasts were significantly lower (approximately 0.006%) than in 293 cells, and no correction was seen in tibialis muscles following rAAV infection. To evaluate the molecular structures of rAAV genomes that might be responsible for gene repair, single-cell injection studies were performed with purified viral DNA in a mutant eGFP target cell line. However, the failure of direct cytoplasm- or nucleus-injected rAAV DNA to facilitate gene repair suggests that some aspect of intracellular viral processing may be required to prime recombinant viral genomes for gene repair events.
MyD88-Dependent Silencing of Transgene Expression During the Innate and Adaptive Immune Response to Helper-Dependent Adenovirus (2009)

Activation of the host innate immune response after systemic administration of adenoviral vectors constitutes a principal impediment to successful clinical gene replacement therapies. Although helper-dependent adenoviruses (HDAds) lack all viral functional genes, systemic administration of a high dose of HDAd still elicits a potent innate immune response in host animals. Toll-like receptors (TLRs) are innate receptors that sense microbial products and trigger the maturation of antigen-presenting cells and cytokine production via MyD88-dependent signaling (except TLR3). Here we show that mice lacking MyD88 exhibit a dramatic reduction in proinflammatory cytokines after intravenous injection of a high dose of HDAd, and show significantly reduced induction of the adaptive immune response when compared with wild-type and TLR2-deficient mice. Importantly, MyD88(-/-) mice also show significantly higher and longer sustained transgene expression than do wild-type mice. Chromatin immunoprecipitation studies using wild-type and MyD88-deficient primary mouse embryonic fibroblasts showed significant MyD88-dependent transcriptional silencing of the HDAd-encoded transgenes. Our results demonstrate that MyD88 signaling, activated by systemic delivery of HDAd, initiates an innate immune response that suppresses transgene expression at the transcriptional level before initiation of the adaptive immune response.
Dietary supplementation with phosphorylated mannans improves growth response and modulates immune function of weanling pigs1 (2004)

Phosphorylated mannans derived from the yeast cell wall of Saccharomyces cerevisiae may beneficially modulate immune function in the weanling pig, possibly providing an alternative to the use of dietary growth-promoting antibiotics. Therefore, in this study, 32 pigs averaging 19 d of age and 5.7 +/- 0.2 kg initial BW were randomly assigned to 16 pens in an environmentally controlled nursery to determine the effects of dietary supplementation with phosphorylated mannans on growth and immune function. Average daily gain and G:F ratio increased (P < 0.05) when pigs were fed diets supplemented with mannans from d 0 to 14 after weaning and in the overall experiment. Percentage of neutrophils was lower (P < 0.08) and percentage of lymphocytes was higher (P < 0.05) in blood from pigs fed mannans than when pigs were fed the basal diet. Lamina propria macrophages isolated from pigs fed diets containing mannans phagocytosed a greater (P < 0.05) number of sheep red blood cells (2.63 +/- 0.11) than did lamina propria macrophages isolated from pigs fed the basal diet (2.31 +/- 0.11). On d 19 after weaning, pigs fed diets supplemented with mannans tended to have a greater (P < 0.10) percentage of CD14+ lamina propria leukocytes than did pigs fed the basal diet. On d 21 following weaning, the percentage of CD14+MHCII+ leukocytes isolated from lamina propria tissue tended (P < 0.10) to be lower when pigs were fed mannans than when pigs were fed the basal diet. Pigs fed diets containing mannans had a lower (P < 0.05) ratio of CD3+CD4+:CD3+CD8+ T lymphocytes isolated from jejunal lamina propria tissue only on d 21 after weaning compared with pigs fed the basal diet. Supplementation of mannans in the diets of weanling pigs improved gain and efficiency, and intermittently affected selected components of the young pigs' immune function both systemically and enterically.
Fecal microbiota transplantation in gastrointestinal diseases. What practicing physicians should know (2015)

Clostridium difficile infection (CDI) is one of the most commonly reported nosocomial pathogens in the United States and Europe, with recent CDI-associated mortality in the United States approaching 30 000 deaths annually. Antibiotics remain the preferred treatment for CDI; however, a minority of patients experience numerous relapses and are treated with restoration of the bowel microbiota, termed fecal microbiota transplantation (FMT). FMT involves the introduction of a fecal suspension from a healthy donor into the gut of the infected patient to cure the CDI and replace depleted components of the gut microbiota. FMT is particularly effective and safe in curing CDI, using a colonoscope or enema to deliver 1 to 2 infusions. Given that 6425 CDIs were reported in Poland in 2014, practicing physicians should understand the benefits and limitations of FMT in CDI as this novel therapy has rapidly advanced to the level of the "standard-of-care" status in Australia, the United States, and many parts of Europe. FMT has been administered either as a suspension in saline, a highly refined liquid product which can be frozen, as lyophilized powder in capsules, and as an encapsulated spore preparation. The ultimate products to reach the market will be shaped by the indications approved by regulatory bodies. At present, the fecal suspension in saline remains the treatment of choice to terminate relapsing and severe CDI, which we will review here. The use of FMT for non-CDI indications, such as inflammatory bowel disease and irritable bowel syndrome, is likely to increase. At present, these indications remain in the domain of research institutions.
Chemical‐ and cuticular phenoloxidase‐ mediated synthesis of cysteinyl–catechol adducts (1989)

Abstract N ‐Acetylcysteine adducts of o ‐benzoquinones derived from catechol, 4‐methylcatechol, and N ‐acetyldopamine were chemically synthesized and characterized by a combination of UV, IR, and NMR spectral studies. Oxidation of catechol, 4‐methylcatechol, and N ‐acetyldopamine by cuticle‐bound phenoloxidase from Sarcophaga bullata in the presence of N ‐acetylcysteine resulted in the formation of covalent adducts between catecholic compounds and N ‐acetylcysteine. Structural identities of these adducts were established by comparison of their HPLC retention time and UV spectra with those of synthetic adducts and by cochromatography with authentic samples. Although insect cuticle is known to contain only trace amounts of cysteine, the in vitro synthesis of quinone cysteine adducts mediated by cuticular phenoloxidase strongly indicates the occurrence of similar reactions in vivo as well and is in support of Pryor's quinone tanning hypothesis.
Association of Muscle Strength With the Risk of Alzheimer Disease and the Rate of Cognitive Decline in Community-Dwelling Older Persons (2009)

These findings suggest a link between muscle strength, AD, and cognitive decline in older persons.
Characterization of broadly pleiotropic phenotypes caused by an hfq insertion mutation in Escherichia coli K‐12 (1994)

The region immediately downstream from the miaA tRNA modification gene at 94.8 min contains the hfq gene and the hflA region, which are important in the bacteriophage Q beta and lambda life cycles. The roles of these genes in bacteria remain largely unknown. We report here the characterization of two chromosomal hfq insertion mutations. An omega (omega) cassette insertion near the end of hfq resulted in phenotypes only slightly different from the parent, although transcript mapping demonstrated that the insertion was completely polar on hflX expression. In contrast, an equally polar omega cassette insertion near the beginning of hfq caused pronounced pleiotropic phenotypes, including decreased growth rates and yields, decreased negative supercoiling of plasmids in stationary phase, increased cell size, osmosensitivity, increased oxidation of carbon sources, increased sensitivity to ultraviolet light, and suppression of bgl activation by hns mutations. hfq::omega mutant phenotypes were distinct from those caused by omega insertions early in the miaA tRNA modification gene. On the other hand, both hfq insertions interfered with lambda phage plaque formation, probably by means of polarity at the hflA region. Together, these results show that hfq function plays a fundamental role in Escherichia coli physiology and that hfq and the hflA-region are in the amiB-mutL-miaA-hfq-hflX superoperon.
Role of calcitonin gene-related peptide in gastric hyperemic response to intragastric capsaicin (1991)

Stimulation of sensory neurons in the rat stomach by intragastric capsaicin leads to a marked rise in gastric mucosal blood flow (GMBF). The gastric mucosa, in particular submucosal blood vessels, is densely innervated by afferent neurons containing peptides, of which calcitonin gene-related peptide (CGRP) is the most potent vasodilator. Using selective ablation of either the vagal or spinal sensory innervation to the stomach by perineural application of capsaicin, and by intra-arterial infusion of the CGRP receptor antagonist hCGRP-(8-37) close to the stomach, we investigated 1) the origin (vagal or spinal) of the sensory neurons and 2) whether CGRP mediates this hyperemic response. Perivagal application of capsaicin to the rat 10-20 days before experiments had no effect on the hyperemic response to intragastric capsaicin. In contrast, periceliac application of capsaicin significantly reduced this response by 60%. Intra-arterial infusion of CGRP (20 pmol/min) close to the stomach produced a marked rise in GMBF and this was completely blocked by hCGRP-(8-37) (500 pmol/min). intra-arterial infusion of hCGRP-(8-37) or its vehicle, bovine serum albumin, had no significant effect on basal GMBF. However, the increment in GMBF in response to intragastric capsaicin was significantly attenuated by 79%. We conclude that 1) spinal sensory neurons innervating the gastric mucosa partially mediate the increase in GMBF induced by intragastric capsaicin and 2) CGRP is the major vasodilator released by these fibers.