gebhart/patrepeval huggingface dataset:
Skeletal Muscle Tissue Engineering Using Isolated Myoblasts on Synthetic Biodegradable Polymers: Preliminary Studies (1999)

Skeletal muscle is responsible for the control of voluntary movement and the maintenance of structural contours of the body. Muscle loss or deficiency is encountered in various pathological states, and attempts to correct them have been employed with limited success. The aim of the present study was to tissue engineer three-dimensional vascularized skeletal muscle using isolated myoblasts attached to synthetic biodegradable polymer for tissue replacement in the enhancement of muscle regeneration. Myoblasts derived from neonatal rats (3-5-day-old), Fisher CDF-F344, were seeded onto polyglycolic acid meshes and implanted into the omentum of syngeneic adult Fisher CDF-F344 rats. Rats were sacrificed on day 30 and day 45 after the transplantation, and the cell-polymer constructs were harvested for morphological analysis. Histological analysis of the constructs were performed by hematoxylin and eosin, and immunohistochemical staining was positive for alpha sarcomeric actin and desmin skeletal muscle marker. Viable myoblasts organized between strands of degrading polymer mesh formed the new tissue, and vascularization of the entire construct was observed. Organization of neomuscle strands surrounded by vascularized tissue composed of degrading polymer and fusing myoblasts demonstrated the ability of myoblast constructs to survive, reorganize and regenerate tissue-like structures. Since myoblast transplantation to date has been limited to the cellular level of replacement, myoblast-polyglycolic acid constructs may be useful in defining the application of tissue engineering for future skeletal muscle transplantations.
Ultrafast studies of single semiconductor and metal nanostructures through transient absorption microscopy (2010)

The past decade has seen tremendous progress in the development of absorption based techniques for studying single semiconductor and metal nanoparticles. These techniques complement the more common emission and Rayleigh scattering measurements. The advantages of absorption-based detection are that a wider range of materials can be examined compared to emission, and smaller particles can be studied than is possible with Rayleigh scattering. These advantages are somewhat offset by increased difficulty. Importantly, by employing absorption based detection with a pump and probe beam, transient absorption experiments can be performed on single nanostructures. This allows dynamics measurements on ultrafast (sub-ps) timescales, and is the focus of this mini-review. These experiments provide information about how processes such as electron–phonon coupling, energy dissipation, and charge carrier trapping vary between nanostructures, as well as how they depend on environment.
Identification of a Class of Small Molecule Inhibitors of the Sirtuin Family of NAD-dependent Deacetylases by Phenotypic Screening (2001)

The yeast transcriptional repressor Sir2p silences gene expression from the telomeric, rDNA, and silent mating-type loci and may play a role in higher order processes such as aging. Sir2p is the founding member of a large family of NAD-dependent deacetylase enzymes, named the sirtuins. These proteins are conserved from prokaryotes to eukaryotes, but most remain uncharacterized, including all seven human sirtuins. A reverse chemical genetic approach would be useful in identifying the biological function of sirtuins in a wide variety of experimental systems, but no cell-permeable small molecule inhibitors of sirtuins have been reported previously. Herein we describe a high throughput, phenotypic screen in cells that led to the discovery of a class of sirtuin inhibitors. All three compounds inhibited yeast Sir2p transcriptional silencing activity in vivo, and yeast Sir2p and human SIRT2 deacetylase activity in vitro. Such specific results demonstrate the utility and robustness of this screening methodology. Structure-activity relationship analysis of the compounds identified a key hydroxy-napthaldehyde moiety that is necessary and sufficient for inhibitory activity. Preliminary studies using one of these compounds suggest that inhibition of sirtuins interferes with body axis formation in Arabidopsis.
In vivo investigation of the placental transfer of 13C-labeled fatty acids in humans (2003)

Placental fatty acid transfer in humans in vivo was studied using stable isotopes. Four pregnant women undergoing cesarean section received 4 h before delivery an oral dose of [(13)C]palmitic acid (PA), [(13)C]oleic acid (OA), [(13)C]linoleic acid (LA), and [(13)C]docosahexaenoic acid (DHA). Maternal blood samples were collected at -4 h (basal), -3 h, -2 h, -1 h, 0 h, and +1 h relative to time of cesarean section. At the time of birth, venous cord blood and placental tissue were collected. Fatty acid composition was determined by gas-liquid chromatography and isotopic enrichment by gas chromatography-combustion-isotope ratio mass spectrometry. (13)C-enrichment of fatty acids in the nonesterified fatty acids (NEFA) of cord plasma tended to be higher than in NEFA of placenta, with statistically significant differences for the nonesterified OA and DHA ([(13)C]PA, 0.024 +/- 0.011 vs. 0.001 +/- 0.001; [(13)C]OA, 0.042 +/- 0.008 vs. 0.005 +/- 0.003; [(13)C]LA, 0.038 +/- 0.010 vs. 0.008 +/- 0.002; [(13)C]DHA, 0.059 +/- 0.009 vs. 0.010 +/- 0.003). The ratio of tracer fatty acid concentrations of placenta to maternal plasma was significantly higher for [(13)C]DHA than for the other fatty acids ([(13)C]PA, 7.1 +/- 1%; [(13)C]OA, 3.8 +/- 0.4%; [(13)C]LA, 9.2 +/- 1.3%; [(13)C]DHA, 25.9 +/- 3.4%). These results suggest that only a part of the placental NEFA participated in fatty acid transfer, and that the placenta showed a preferential accretion of DHA relative to the other fatty acids.
Current and future approaches for control of graft-versus-host disease (2008)

Graft-versus-host disease (GVHD), both acute and chronic, remains one of the major barriers to improving outcomes after allogeneic stem cell transplantation. The pathophysiology of GVHD is complex and incompletely understood. GVHD is believed to arise from the interaction of: tissue damage and proinflammatory cytokines causing activation of antigen-presenting cells (APCs, donor T-cell activation by APCs and cytokines and host tissue injury by effector T lymphocytes and proinflammatory cytokines. There is also a role for additional lymphocyte subtypes (naive and memory T cells, regulatory T cells, natural killer T cells and B cells) in GVHD pathogenesis. Strategies to improve donor-recipient HLA match, and to minimize conditioning toxicity, cytokine release and APC and effector T-lymphocyte activation, will likely improve prophylaxis of acute (and possibly chronic) GVHD. Therapy of established acute and chronic GVHD is still heavily dependent on corticosteroids, despite their limited efficacy and considerable toxicity. Novel agents (and/or combinations of agents) comprising pharmacologic, biologic and cellular therapies targeting specific steps or subsets involved in immune activation will likely comprise future advances in GVHD control. This article reviews the current state of knowledge regarding the prevention and treatment of acute and chronic GVHD. Novel approaches currently undergoing evaluation are also highlighted.
Industrial Upgrading Effect of OFDI of Sichuan Province of China (2018)

Despite the upgrading of industrial structure is not the direct purpose of OFDI, the experience of many countries shows that there is a connection between them. Through the method of fixed effect and SGMM, this paper aims to estimate and analysis the industrial upgrading effect of OFDI of Sichuan province of China, using the panel data of 31 districts of China from 2003 to 2016. From the empirical results we come to the conclusion that OFDI can promote the optimization and upgrading of industrial structure in China and in Sichuan province. For every 1% increase in OFDI, China&amp;rsquo;s industrial structure index rose 0.00182% and Sichuan&amp;rsquo;s industrial structure index rose 0.0237%.
Homotypic and Heterotypic Epitope-Specific Antibody Responses in Adult and Infant Rotavirus Vaccinees: Implications for Vaccine Development (1990)

Sera from infants and adults who received a live, attenuated monovalent rotavirus vaccine of serotype 1, 2, 3, or 4 VP7 specificity and rhesus rotavirus (RRV) VP4 specificity were analyzed for serotype-specific antibody responses by an epitope blocking immunoassay (EBA) and by neutralization. Although the assays correlated well, responses to the individual neutralization proteins or to different defined antigenic sites on the same protein could be distinguished only by EBA. In general, adult vaccinees exhibited both a homotypic response to the immunizing strain and a heterotypic response to other serotypes. Infant vaccinees less than 6 months old also had a homotypic antibody response but developed significantly fewer heterotypic responses than adults (1.2% and 59%, respectively; P less than .0001). In addition, postvaccination sera from vaccinees who developed naturally occurring rotavirus diarrhea during an efficacy trial of RRV (MMU-18006) or RIT 4237 vaccine were analyzed for serotype-specific responses. The data suggest that the inability to mount a heterotypic antibody response to the infecting serotypes in young infants may have been an important factor in failure of the vaccines to induce protection.
Automatic Image Enhancement by Content Dependent Exposure Correction (2004)

We describe an automatic image enhancement technique based on features extraction methods. The approach takes into account images in Bayer data format, captured using a CCD/CMOS sensor and/or 24-bit color images; after identifying the visually significant features, the algorithm adjusts the exposure level using a "camera response"-like function; then a final HUE reconstruction is achieved. This method is suitable for handset devices acquisition systems (e.g., mobile phones, PDA, etc.). The process is also suitable to solve some of the typical drawbacks due to several factors such as poor optics, absence of flashgun, and so forth.
In Vitro Antiviral Activity and Single-Dose Pharmacokinetics in Humans of a Novel, Orally Bioavailable Inhibitor of Human Rhinovirus 3C Protease (2005)

(E)-(S)-4-((S)-2-{3-[(5-methyl-isoxazole-3-carbonyl)-amino]-2-oxo-2H-pyridin-1-yl}-pent-4-ynoylamino)-5-((S)-2-oxo-pyrrolidin-3-yl)-pent-2-enoic acid ethyl ester (Compound 1) is a novel, irreversible inhibitor of human rhinovirus (HRV) 3C protease {inactivation rate constant (Kobs/[I]) of 223,000 M-1s-1}. In cell-based assays, Compound 1 was active against all HRV serotypes (35 of 35), HRV clinical isolates (5 of 5), and related picornaviruses (8 of 8) tested with mean 50% effective concentration (EC50) values of 50 nM (range, 14 to 122 nM), 77 nM (range, 72 to 89 nM), and 75 nM (range, 7 to 249 nM), respectively. Compound 1 inhibited HRV 3C-mediated polyprotein processing in infected cells in a concentration-dependent manner, providing direct confirmation that the cell-based antiviral activity is due to inhibition of 3C protease. In vitro and in vivo nonclinical safety studies showed Compound 1 to be without adverse effects at maximum achievable doses. Single oral doses of Compound 1 up to 2,000 mg in healthy volunteers were found to be safe and well tolerated in a phase I-ascending, single-dose study. Compound 1 estimated free observed maximum concentration in plasma (Cmax) for 500-, 1,000-, and 2,000-mg doses were higher than the protein binding-corrected EC50 required to inhibit 80% of the HRV serotypes tested. Treatment of HRV 52-infected cells with one to five 2-h pulses of 150 nM Compound 1 (corresponding to the Cmax at the 500-mg dose) was sufficient to effect a significant reduction in viral replication. These experiments highlight Compound 1 as a potent, orally bioavailable, irreversible inhibitor of HRV 3C protease and provide data that suggest that Cmax rather than the Cmin might be the key variable predicting clinical efficacy.
The nuclear pore complex protein Tpr is a common autoantigen in sera that demonstrate nuclear envelope staining by indirect immunofluorescence (2004)

We studied the autoantigen targets of 75 human sera that had antibodies to the nuclear envelope (NE) as identified by indirect immunofluorescence (IIF) on HEp-2 cells. Several different IIF staining patterns could be identified when antibodies to different components of the nuclear membrane (NM) and nuclear pore complexes (NuPC) were identified: a smooth membrane pattern characteristic of antibodies to nuclear lamins, a punctate pattern typical of antibodies to the nuclear pore complex and more complex patterns that included antibodies to nuclear and cytoplasmic organelles. Western immunoblotting of isolated nuclear and NE proteins and immunoprecipitation of radiolabelled recombinant proteins prepared by using the full-length cDNAs of the Translocated promoter region (Tpr), gp210 and p62 were used to identify specific autoantibody targets. Fifty-two of the 75 (70%) sera bound to Tpr, 25 (33%) bound to lamins A, B or C, 15 (20%) reacted with gp210 and none reacted with p62. Sixteen (21%) did not react with any of the NE components tested in our assays. The clinical features of 37 patients with anti-NE showed that there were 34 females and three males with an age range of 16-88 years (mean 59 years). The most frequent clinical diagnosis (9/37 = 24%) was autoimmune liver disease (ALD; two with primary biliary cirrhosis), followed by seven (19%) with systemic lupus erythematosus (SLE), four (11%) with a motor and/or sensory neuropathy, three (8%) with anti-phospholipid syndrome (APS), two with systemic sclerosis (SSc), two with Sjögren's syndrome (SjS), and others with a variety of diagnoses. This report indicates that Tpr, a component of the NuPC, is a common target of human autoantibodies that react with the NE.
Inhibition of sphingolipid biosynthesis by fumonisins. Implications for diseases associated with Fusarium moniliforme (1991)

Culture materials and grains contaminated with certain isolates of Fusarium moniliforme cause equine leucoencephalomalacia, porcine pulmonary edema syndrome, and liver cancer in rats. The causative agents are thought to be a family of compounds called fumonisins, which bear considerable structural similarity to the long-chain (sphingoid) base backbones of sphingolipids. Incubation of rat hepatocytes with fumonisins inhibited incorporation of [14C]serine into the sphingosine moiety of cellular sphingolipids with an IC50 of 0.1 microM for fumonisin B1. In contrast, fumonisin B1 increased the amount of the biosynthetic intermediate sphinganine, which suggests that fumonisins inhibit the conversion of [14C]sphinganine to N-acyl-[14C]sphinganines, a step that is thought to precede introduction of the 4,5-trans double bond of sphingosine (Merrill, A.H., Jr. and Wang, E. (1986) J. Biol. Chem. 261, 3764-3769). In agreement with this mechanism, fumonisin B1 inhibited the activity of sphingosine N-acyltransferase (ceramide synthase) in rat liver microsomes with 50% inhibition at approximately 0.1 microM and reduced the conversion of [3H]sphingosine to [3H]ceramide by intact hepatocytes. As far as we are aware, this is the first discovery of a naturally occurring inhibitor of this step of sphingolipid metabolism. These findings suggest that disruption of the de novo pathway of sphingolipid biosynthesis may be a critical event in the diseases that have been associated with consumption of fumonisins.
The yeast repeated element sigma contains a hormone-inducible promoter. (1987)

A genomic clone (lambda ScG7) from Saccharomyces cerevisiae encoded a 650-nucleotide poly(A)-containing [poly(A)+] RNA that was about 50 times more abundant in MATa cells that had been exposed to the peptide pheromone alpha-factor than in untreated cells. This RNA was transcribed from a cluster of repetitive sequences: both intact and truncated delta and sigma elements adjacent to a tRNATrp gene. Strand-specific probes indicated that this RNA initiated within an intact sigma element and contained sigma sequences at its 5' end. MATa cells produced two other prominent poly(A)+ RNAs (500 and 5,300 bases) in response to alpha-factor that were homologous to the same strand of sigma but transcribed from other locations in the genome. Induction of the sigma-related transcripts was rapid, was not blocked by inhibition of protein synthesis, required a functional receptor (STE2 gene product), and hence appeared to be a primary response to pheromone. Pulse-labeling confirmed that accumulation of sigma RNA following alpha-factor administration was accounted for by an increase in its rate of transcription. The sigma RNAs also were induced in MAT alpha cells that had been treated with a-factor, but were not present at significant levels in MATa/MAT alpha diploids. In MATa cells transformed with a plasmid in which the lambda ScG7 sigma element was inserted just upstream of a gene coding for the intracellular form of invertase (SUC2) lacking its own promoter, a new poly(A)+ RNA (2.2 kilobases) appeared in response to alpha-factor that hybridized to both sigma and SUC2 probes, and intracellular invertase activity was elevated about 10-fold within 30 min. Primer extension showed that transcription from the hybrid gene initiated exclusively within the sigma sequence (117 nucleotides from the 3' end of the element).
Distinct Roles for the OX40-OX40 Ligand Interaction in Regulatory and Nonregulatory T Cells (2004)

The OX40 (CD134) molecule is induced primarily during T cell activation and, as we show in this study, is also expressed on CD25+CD4+ regulatory T (Treg) cells. A necessary role for OX40 in the development and homeostasis of Treg cells can be inferred from the reduced numbers of the cells present in the spleens of OX40-deficient mice, and their elevated numbers in the spleens of mice that overexpress the OX40 ligand (OX40L). The homeostatic proliferation of Treg cells following transfer into lymphopenic mice was also found to be potentiated by the OX40-OX40L interaction. Suppression of T cell responses by Treg cells was significantly impaired in the absence of OX40, indicating that, in addition to its homeostatic functions, OX40 contributes to efficient Treg-mediated suppression. However, despite this, we found that CD25-CD4+ T cells became insensitive to Treg-mediated suppression when they were exposed to OX40L-expressing cells, or when they were treated with an agonistic OX40-specific mAb. OX40 signaling could also abrogate the disease-preventing activity of Treg cells in an experimental model of inflammatory bowel disease. Thus, although the data reveal important roles for OX40 signaling in Treg cell development, homeostasis, and suppressive activity, they also show that OX40 signals can oppose Treg-mediated suppression when they are delivered directly to Ag-engaged naive T cells.
13C Metabolic Flux Analysis for Systematic Metabolic Engineering of S. cerevisiae for Overproduction of Fatty Acids (2016)

Efficient redirection of microbial metabolism into the abundant production of desired bioproducts remains non-trivial. Here, we used flux-based modeling approaches to improve yields of fatty acids in <i>Saccharomyces cerevisiae</i>. We combined <sup>13</sup>C labeling data with comprehensive genome-scale models to shed light onto microbial metabolism and improve metabolic engineering efforts. We concentrated on studying the balance of acetyl-CoA, a precursor metabolite for the biosynthesis of fatty acids. A genome-wide acetyl-CoA balance study showed ATP citrate lyase from <i>Yarrowia lipolytica</i> as a robust source of cytoplasmic acetyl-CoA and malate synthase as a desirable target for downregulation in terms of acetyl-CoA consumption. These genetic modifications were applied to <i>S. cerevisiae</i> WRY2, a strain that is capable of producing 460 mg/L of free fatty acids. With the addition of ATP citrate lyase and downregulation of malate synthase, the engineered strain produced 26% more free fatty acids. Further increases in free fatty acid production of 33% were obtained by knocking out the cytoplasmic glycerol-3-phosphate dehydrogenase, which flux analysis had shown was competing for carbon flux upstream with the carbon flux through the acetyl-CoA production pathway in the cytoplasm. In total, the genetic interventions applied in this work increased fatty acid production by ~70%.
Interaction of the chick oviduct progesterone receptor with deoxyribonucleic acid (1981)

The purified DNA binding component (receptor A) of the chick oviduct progesterone receptor has been analyzed for its ability to bind to the cloned ovalbumin gene and to plasmid DNA of various structural compositions. The rapid equilibrium filter adsorption assay of Riggs et al. [Riggs, A. D., Suzuki, H., & Bourgeois, S. (1970) J. Mol. Biol. 48, 67] has been used to demonstrate high affinity binding of the protein to DNA (Kdiss = 10(-10) M at 50 mM KCl, pH 7.2). Studies of association rates are consistent with equilibrium measurements (t 1/2 = 40-80 min). Association of purified receptor with DNA and the kinetics of the interaction have been verified independently by velocity sedimentation techniques. Direct binding assays were performed with the ovalbumin structural gene (cDNA), the entire natural ovalbumin gene containing seven intervening sequences, and various ovalbumin gene fragments coding for the 5' end of the nuclear precursor RNA, intron-exon junctions, and the 3'-noncoding region of the gene. No DNA-sequence specificity was identified for the binding of the receptor protein to any region of ovalbumin gene DNA. In contrast, the structural integrity of the DNA template greatly affected receptor binding. The poorest affinity was to supercoiled DNA and to blunt end, linear duplex gene fragments. The receptor bound saturably to DNA containing limited nicks but became nonsaturable as nicks were increased. Binding of the protein to double-stranded DNA increased susceptibility of the DNA to digestion by the enzyme S1, a single strand specific nuclease. On the basis of preferential receptor binding to single-stranded DNA, a possible mechanism involving DNA helix destabilization is discussed.
The adenovirus L3 23-kilodalton proteinase cleaves the amino-terminal head domain from cytokeratin 18 and disrupts the cytokeratin network of HeLa cells (1993)

Immunofluorescence studies revealed that adenovirus induces a reorganization of the cytokeratin system in lytically infected HeLa cells. At 24 h postinfection, the cytokeratin network began to disassemble into prominent spheroid globules. By 36 h postinfection, host cell lysis occurred, accompanied by the formation of perinuclear cytokeratin clumps and additional spheroid globules. Immunoblots detected 41- and 44-kDa fragments of cytokeratin 18 and reduced levels of cytokeratin 7 at 24 and 36 h postinfection. Cytokeratin proteins isolated from HeLa cells at 36 h postinfection were deficient in filament polymerization. The 41-kDa proteolytic cytokeratin 18-specific fragment was purified, and its amino-terminal sequence was determined to be GGIQNEKETM. These residues correspond to amino acids 74 through 83 of cytokeratin 18, identifying a cleavage site at the junction of the globular head domain and the alpha-helical rod domain. Moreover, this truncation event occurs at a consensus cleavage site for the adenovirus L3 23-kDa proteinase. The temperature-sensitive mutant H2-ts1, which contains a mutation in the proteinase, neither induced cleavage of cytokeratin 18 nor precipitated the formation of spheroid globules during lytic infection at the nonpermissive temperature. The active proteinase is therefore required for cleavage of cytokeratin 18 and morphological rearrangement of the cytokeratins. We suggest that disruptions in the cytokeratin system weaken the mechanical integrity of the cell, thus promoting host cell lysis and release of progeny virions.