gebhart/patrepeval huggingface dataset:
Adiponectin Sensitizes Insulin Signaling by Reducing p70 S6 Kinase-mediated Serine Phosphorylation of IRS-1 (2007)

Adiponectin functions as an insulin sensitizer, and yet the underlying molecular mechanism(s) remains largely unknown. We found that treating C2C12 myotubes with adiponectin or rapamycin enhanced the ability of insulin to stimulate IRS-1 tyrosine phosphorylation and Akt phosphorylation, concurrently with reduced p70 S6 kinase phosphorylation at Thr389 as well as IRS-1 phosphorylation at Ser302 and Ser636/639. Overexpression of dominant-negative AMP kinase (AMPK), but not dominant-negative p38 MAPK, reduced the insulin-sensitizing effect of adiponectin. Rapamycin, but not adiponectin, enhanced insulin-stimulated Akt phosphorylation in HeLa cells, which lack LKB1, and exogenous expression of LKB1 in HeLa cells rescued the insulin-sensitizing effect of adiponectin. Finally, overexpression of wild-type Rheb (Ras homology-enriched in brain) or the TSC2 mutant lacking the AMPK phosphorylation site (TSC2S1345A) inhibited the insulin-sensitizing effect of adiponectin in C2C12 cells. These results indicate that activation of the LKB1/AMPK/TSC1/2 pathway alleviates the p70 S6 kinase-mediated negative regulation of insulin signaling, providing a mechanism by which adiponectin increases insulin sensitivity in cells.
Changes in Vaginal Bacterial Flora During the Oestrous Cycle of the Mouse (1991)

The vaginal bacterial flora of MF1 mice was studied using bacteriological culturing techniques, light microscopy and scanning electron microscopy, and results related to stage in oestrous cycle as determined by cytological smears. Total viable bacterial numbers at metoestrus and dioestrus were lower than at oestrus and proestrus. Bacteria of the genera Streptococcus, Lactobacillus, Corynebacterium, Staphylococcus and Actinomyces were consistently isolated at all stages of the cycle, although at proestrus and oestrus the Streptococcus and Lactobacillus mainly contributed to the increase in bacterial numbers. These results are associated with vaginal cellular changes at various stages of the oestrous cycle. Metabolic end-products produced by the vaginal bacterial flora may contribute in signalling the sexual status of the mice to receptive males.
Effects of RuPeng15 Powder (RPP15) on Monosodium Urate Crystal-Induced Gouty Arthritis in Rats (2015)

RuPeng15 Powder (RPP15) is a herbal multicompound remedy that originates from traditional Tibetan medicine and possesses antigout, anti-inflammatory, and antihyperuricemic properties based on the traditional conceptions. The present study was undertaken to evaluate the therapeutic effect of PRP15 in rat gouty arthritis induced by monosodium urate (MSU) crystals. In the present study, we found that treatment with RPP15 (0.4, 0.8, and 1.2 g/kg) in rats with gouty arthritis induced by MSU crystals significantly attenuated the knee swelling. Histomorphometric and immunohistochemistry analyses revealed that MSU-induced inflammatory cell infiltration and the elevated expressions of nuclear transcription factor-κB p65 (NF-κB p65) in synovial tissues were significantly inhibited, and enzyme-linked immunosorbent assay (ELISA) result showed that MSU-induced high levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-8 (IL-8) in synovial fluid were reduced by treatment with RPP15 (0.4, 0.8, and 1.2 g/kg). We conclude that RPP15 may be a promising candidate for the development of a new treatment for gout and its activity of antigout may be partially related to inhibiting TNF-α, IL-1β, IL-8, and NF-κB p65 expression in the synovial tissues.
Cell-mediated killing: effector mechanisms and mediators (1990)

Cytolytic T lymphocytes and natural killer cells appear to mediate cell killing by several different mechanisms. In one mechanism, a pore-forming protein, called perforin or cytolysin, is exocytosed by the effector cell and is inserted into the plasma membrane of the target cells, thereby collapsing its permeability barrier. Alternatively, the cytolytic cells activate a pathway of programmed cell death that causes specific fragmentation of target cell DNA. The physiological circumstances that determine which mechanism will be employed by the effector cells have not yet been fully determined. Recent experiments suggest that perforin is employed in situations in which there are high local concentrations of interleukin-2, such as cancer and acute viral infections, while a role for the programmed cell death pathway remains to be elucidated.
Coupling of modes analysis of resonant channel add-drop filters (1999)

The operation principle of resonant channel add-drop filters based on degenerate symmetric and antisymmetric standing-wave modes has been described elsewhere using group theoretical arguments. In this paper, the analysis is carried out using coupling of modes in time. A possible implementation of such a filter is a four-port system utilizing a pair of identical single-mode standing wave resonators. The analysis allows a simple derivation of the constraints imposed on the design parameters in order to establish degeneracy. Numerical simulations of wave propagation through such a filter are also shown, as idealized by a two-dimensional geometry.
Engineering exosomes toward folate receptor expressing cells (2017)

In this project it has been evaluated a new drug delivery system based on the use of natural vehicles called Extracellular Vesicles (EV). Particularly, these vesicles have been modified through the use of a targeting agent (FA-PEG3,4Da-DSPE) expressed on their surface in orders to exploit both the passive and active targeting of the tumor microenviroment.
Segmental genomic replacement in embryonic stem cells by double lox targeting (1999)

We have applied Cre-mediated double lox recombination to embryonic stem (ES) cells to facilitate repeated knock-ins at a target locus, thus helping to assure correct temporal and spatial transgene expression in mice. Using homologous recombination, we inserted a double lox cassette a few nucleo-tides before the authentic ATG start of MHL-1, the gene coding for the major subunit of the asialoglycoprotein receptor. The cassette carries a marker gene bounded by heterospecific lox sites that cannot recombine with each other, but which can undergo recombination with like sites on an incoming double lox targeting vector. Cre-mediated replacement of the lox-delimited genomic segment at MHL-1 with targeting DNA occurs at a frequency three times that of random DNA integration and is sufficiently robust that correctly targeted ES colonies can be identified by PCR screening without relying on any drug selection procedure. Moreover, double lox recombination at the MHL-1 locus is not dependent on the presence or absence of a transcriptionally active promoter at the genomic target. The strategy and vectors described here are generally applicable to designing double lox targeted knock-ins at any locus in ES cells and should prove useful in more precise molecular engineering of the mouse genome.
Turnover Rates in Heterogeneous Catalysis (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTurnover Rates in Heterogeneous CatalysisM. BoudartCite this: Chem. Rev. 1995, 95, 3, 661–666Publication Date (Print):May 1, 1995Publication History Published online1 May 2002Published inissue 1 May 1995https://pubs.acs.org/doi/10.1021/cr00035a009https://doi.org/10.1021/cr00035a009research-articleACS PublicationsRequest reuse permissionsArticle Views15041Altmetric-Citations489LEARN 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
Vasodilator Compounds Derived from Plants and Their Mechanisms of Action (2013)

The present paper reviews vasodilator compounds isolated from plants that were reported in the past 22 years (1990 to 2012) and the different mechanisms of action involved in their vasodilator effects. The search for reports was conducted in a comprehensive manner, intending to encompass those metabolites with a vasodilator effect whose mechanism of action involved both vascular endothelium and arterial smooth muscle. The results obtained from our bibliographic search showed that over half of the isolated compounds have a mechanism of action involving the endothelium. Most of these bioactive metabolites cause vasodilation either by activating the nitric oxide/cGMP pathway or by blocking voltage-dependent calcium channels. Moreover, it was found that many compounds induced vasodilation by more than one mechanism. This review confirms that secondary metabolites, which include a significant group of compounds with extensive chemical diversity, are a valuable source of new pharmaceuticals useful for the treatment and prevention of cardiovascular diseases.
Correlation between in vitro and in vivo parameters of commercial paracetamol tablets. (2001)

Three leading and competitive commercial products of paracetamol tablets coded as brands A, B and C (A, being the innovator product) in the country were evaluated for their in vitro properties and in vivo comparative bioavailability. The studies included chemical equivalence, hardness, disintegration time, dissolution rate and systemic availability among eight healthy volunteers. The disintegration times were 2.1 min for brand A, 5.7 min for brand B and 36.2 min for brand C. The dissolution rate (T70) were 33.0 min, 74.5 min and 56.5 min for brands A, B and C, respectively. While brand A passed all the in vitro tests as specified in the official monograph, brand B failed only the dissolution rate test and brand C failed both the disintegration and dissolution tests. These significant differences observed among the products after in vitro tests were not reflected in the in vivo availability. While the absorption rate (indicated by tmax) of brand C was significantly faster (i.e. shorter) than those of Brands A and B, the extent of absorption (indicated by AUC) was comparable among the three brands. The relative bioavailabilities (with respect to brand A) were 92 and 91% for brands B and C, respectively indicating that the products were bioequivalent. Comparison of the in vitro and in vivo data suggest that the systemic absorption of paracetamol may not be dissolution--rate limited and that using in vitro dissolution rate studies alone to establish bioequivalency of paracetamol tablets should be done with caution.
A PDMS Microfluidic Spotter for Fabrication of Lipid Microarrays (2005)

A PDMS microfluidic spotter system has been developed for the patterning of lipid microarrays that require individually addressing each spot area and high spot density. Microarray spot concentration and uniformity are improved by forming array spots through continuous flow whereby a greater amount of lipid in solution will come in contact with and have the opportunity to bind to the substrate surface. Additionally, flow deposition offers more control over spot formation, since the flow rates and deposition times could be uniquely varied for each spot, producing spots with unique concentrations on the surface. The system is significant in that it facilitates the fabrication of high-density arrays with more dilute lipid solutions, which are difficult and sometimes prohibitively expensive to isolate in sufficient concentration for solid pin and ink-jet spotting. Preliminary test deposition using a fluorescent dye has demonstrated a 5-fold increase in deposition density as compared to conventional pin spotting.
Mechanistic Constraints on Diversity in Human V(D)J Recombination (1996)

We have analyzed a large collection of coding junctions generated in human cells. From this analysis, we infer the following about nucleotide processing at coding joints in human cells. First, the pattern of nucleotide loss from coding ends is influenced by the base composition of the coding end sequences. AT-rich sequences suffer greater loss than do GC-rich sequences. Second, inverted repeats can occur at ends that have undergone nucleolytic processing. Previously, inverted repeats (P nucleotides) have been noted only at coding ends that have not undergone nucleolytic processing, this observation being the basis for a model in which a hairpin intermediate is formed at the coding ends early in the reaction. Here, inverted repeats at processed coding ends were present at approximately twice the number of junctions as P nucleotide additions. Terminal deoxynucleotidyl transferase (TdT) is required for the appearance of the inverted repeats at processed ends (but not full-length coding ends), yet statistical analysis shows that it is virtually impossible for the inverted repeats to be polymerized by TdT. Third, TdT additions are not random. It has long been noted that TdT has a G utilization preference. In addition to the G preference, we find that TdT adds strings of purines or strings of pyrimidines at a highly significant frequency. This tendency suggests that nucleotide-stacking interactions affect TdT polymerization. All three of these features place constraints on the extent of junctional diversity in human V(D)J recombination.
How is pluripotency determined and maintained? (2007)

Mouse embryonic stem (ES) cells are pluripotent, as they have the ability to differentiate into the various cell types of a vertebrate embryo. Pluripotency is a property of the inner cell mass (ICM), from which mouse ES cells are derived, and of the epiblast of the blastocyst. Recent extensive molecular studies of mouse ES cells have revealed the unique molecular mechanisms that govern pluripotency. These studies show that ES cells continue to self-renew because of a self-organizing network of transcription factors that prevents their differentiation and promotes their proliferation, and because of epigenetic processes that might be under the control of the pluripotent transcription factor network.
Rich Models for Steganalysis of Digital Images (2012)

We describe a novel general strategy for building steganography detectors for digital images. The process starts with assembling a rich model of the noise component as a union of many diverse submodels formed by joint distributions of neighboring samples from quantized image noise residuals obtained using linear and nonlinear high-pass filters. In contrast to previous approaches, we make the model assembly a part of the training process driven by samples drawn from the corresponding cover- and stego-sources. Ensemble classifiers are used to assemble the model as well as the final steganalyzer due to their low computational complexity and ability to efficiently work with high-dimensional feature spaces and large training sets. We demonstrate the proposed framework on three steganographic algorithms designed to hide messages in images represented in the spatial domain: HUGO, edge-adaptive algorithm by Luo <etal xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"/> <citerefgrp xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <citeref refid="ref32"/></citerefgrp> , and optimally coded ternary <formula formulatype="inline" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex Notation="TeX">$\pm {\hbox{1}}$</tex></formula> embedding. For each algorithm, we apply a simple submodel-selection technique to increase the detection accuracy per model dimensionality and show how the detection saturates with increasing complexity of the rich model. By observing the differences between how different submodels engage in detection, an interesting interplay between the embedding and detection is revealed. Steganalysis built around rich image models combined with ensemble classifiers is a promising direction towards automatizing steganalysis for a wide spectrum of steganographic schemes.
Molecular characterization and spatial distribution of SAP97, a novel presynaptic protein homologous to SAP90 and the Drosophila discs-large tumor suppressor protein (1995)

Synapses are highly specialized sites of cell-cell contact involved in signal transfer. The molecular mechanisms modulating the assembly and stability of synapses are unknown. We previously reported the identification of a 90 kDa synapse-associated protein, SAP90, that is localized at the presynaptic termini of inhibitory GABAergic synapses. SAP90 is a mosaic protein composed of three 90 amino acid residue repeats, an SH3 domain and a region homologous to guanylate kinases. SAP90 shares domain specific homology with a family of proteins involved in the assembly and possibly stability of sites of cell contact. These include the product of the lethal(1) discs-large-1 (dlgA) tumor suppressor gene and the zonula occludens proteins ZO-1, ZO-2. The further characterization of cDNA clones encoding components of synaptic junctions has lead to the identification of a 97 kDa protein, called SAP97, that exhibits a strong overall sequence similarity to SAP90. The present study was undertaken to determine the spatial distribution of SAP97, and to reveal further clues to the possible roles of these proteins in synapses. Light and immunoelectron microscopic analysis of the rat hippocampal formation revealed that SAP97 is localized in the presynaptic nerve termini of excitatory synapses. In other brain regions, SAP97 is found in and along bundles of unmyelinated axons. SAP97 is not restricted to the CNS, but is also present at the basal lateral membrane between a variety of epithelial cells. In cultured T84 cells, it is restricted to the cytoplasmic surface of the plasma membranes between adjacent cells, but not at the edges of cells lacking cell-cell contact suggesting a role for SAP97 in cell adhesion. These data suggest that members of the SAP90/SAP97 subfamily may be involved in the site specific assembly, stability or functions of membrane specialization at sites of cell-cell contact.
Intranasal delivery of neurotrophic factors BDNF, CNTF, EPO, and NT-4 to the CNS (2009)

Injury to the central nervous system (CNS) generally results in significant neuronal death and functional loss. In vitro experiments have demonstrated that neurotrophic factors such as brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and neurotrophin-4/5 (NT-4/5) can promote neuronal survival. However, delivery to the injured CNS is difficult as these large protein molecules do not efficiently cross the blood-brain barrier. Intranasal delivery of 70 microg [(125)I]-radiolabeled BDNF, CNTF, NT-4, or erythropoietin (EPO) resulted in 0.1-1.0 nM neurotrophin concentrations within 25 min in brain parenchyma. In addition, not only did these neurotrophic factors reach the CNS, they were present in sufficient concentrations to activate the prosurvival PI3Kinase/Akt pathway, even where lower levels of neurotrophic factors were measured. Currently traumatic, ischemic and compressive injuries to the CNS have no effective treatment. There is potential clinical relevancy of this method for rescuing injured CNS tissues in order to maintain CNS function in affected patients. The intranasal delivery method has great clinical potential due to (1) simplicity of administration, (2) noninvasive drug administration, (3) relatively rapid CNS delivery, (4) ability to repeat dosing easily, (5) no requirement for drug modification, and (6) minimal systemic exposure.
Anomalous Fluorescence Enhancement of Cy3 and Cy3.5 versus Anomalous Fluorescence Loss of Cy5 and Cy7 upon Covalent Linking to IgG and Noncovalent Binding to Avidin (2000)

This study provides a critical examination of protein labeling with Cy3, Cy5, and other Cy dyes. Two alternate situations were tested. (i) Antibodies were covalently labeled with Cy dye succinimidyl ester at various fluorophore/protein ratios and the fluorescence of the labeled antibodies was compared to that of free Cy dye. (ii) Fluorescent biotin derivatives were synthesized by derivatizing ethylenediamine with one biotin and one Cy3 (or Cy5) residue. The fluorescence properties of these biotin-Cy dye conjugates were examined at all ligand/(strept)avidin ratios (0 </= n </= 4). The results showed an astounding discrepancy between Cy3 and Cy5: Cy3-labeled antibodies fluoresced very well, even at high Cy3/protein ratios, and the same applied to (strept)avidin with up to four bound biotin-Cy3 conjugates. In contrast, antibodies with six covalently bound Cy5 labels (obtained with the recommended procedure) were almost nonfluorescent, only at 2-3 Cy5 labels/IgG some moderate fluorescence was obtained. By analogy, the biotin-Cy3 conjugate fluoresced intensely, even at high ligand/avidin ratio, in contrast to the weakly fluorescing biotin-Cy5 conjugate. Three mechanisms are responsible for the discrepancy between Cy3 and Cy5. (i) Attachment of Cy3 to a protein's surface causes an anomalous enhancement in fluorescence (by 2-3-fold) while no enhancement occurs with Cy5. (ii) Mutual quenching of IgG-bound Cy dyes by resonance energy transfer is much more pronounced for Cy5 labels than for Cy3. (iii) In IgG with six bound Cy5 labels, about one-third of the labels adopt a nonfluorescent state which is characterized by a large UV-vis absorption maximum at 600 nm instead of at 650 nm. Cy3.5 was found to mimick the properties of Cy3, while Cy7, and to some extent also Cy5.5, were similar to Cy5. In conclusion the Cy dye series is divided into two groups: Antibodies with multiple Cy3 or Cy3.5 labels yield bright fluorescence while extensive quenching occurs in antibodies labeled with Cy5 and Cy7.
Emerging applications of fluorescence spectroscopy to cellular imaging: lifetime imaging, metal-ligand probes, multi-photon excitation and light quenching. (1996)

Advances in time-resolved fluorescence spectroscopy can be applied to cellular imaging. Fluorescence lifetime imaging microscopy (FLIM) creates image contrast based on the decay time of sensing probes at each point in a two-dimensional image. FLIM allows imaging of Ca2+ and other ions without the need for wavelength-ratiometric probes. Ca2+ imaging can be performed by FLIM with visible wavelength excitation. Instrumentation for FLIM is potentially simple enough to be present in most research laboratories. Applications of fluorescence are often limited by the lack of suitable fluorophores. New, highly photostable probes allow off-gating of the prompt autofluorescence, and measurement of rotational motion of large macromolecules. These luminescent metal-ligand complexes will become widely utilized. Modern pulse lasers allow new experiments based on non-linear phenomena. With picosecond and femtosecond lasers fluorophores can be excited by simultaneous absorption of two or three photons. Hence, Ca2+ probes, membrane probes, and even intrinsic protein fluorescence can be excited with red or near infrared wavelengths, without ultraviolet lasers or optics. Finally, light itself can be used to control the excited state population. By using light pulses whose wavelength overlaps the emission spectrum of a fluorophore one can modify the excited state population and orientation. This use of non-absorbed light to modify emission can have wide reaching applications in cellular imaging.