gebhart/patrepeval huggingface dataset:
Do long-chain n-3 fatty acids reduce arterial stiffness? A meta-analysis of randomised controlled trials (2011)

Fish oils, rich in long-chain n-3 PUFA, are known to reduce various risk factors for CVD. However, conclusive evidence regarding the benefits of n-3 on arterial stiffness, a risk factor for CVD, has not yet been established. Consequently, we conducted the first study aimed to quantify the effects of n-3 supplementation on arterial stiffness through meta-analysis. Multiple databases and clinical trial registries were systematically searched up until September 2010 for randomised and controlled adult human clinical trials to investigate the effects of long-chain n-3 fatty acids on arterial stiffness. No limits were set on dosage sizes or sample characteristics. A total of ten n-3 trials met the final inclusion criteria; four using pulse wave velocity (PWV) and six using arterial compliance, measured as capacitive compliance or systemic arterial compliance, as respective outcome measures. Meta-analysis revealed that n-3 was statistically significant in effectively improving both PWV (g = 0·33; 95 % CI 0·12, 0·56; P < 0·01) and arterial compliance (g = 0·48; 95 % CI 0·24, 0·72; P < 0·001). There was no evidence of heterogeneity or publication bias. Results were not influenced by changes in blood pressure, heart rate or BMI. The findings of the present study reveal that supplementation with n-3 offers a scientifically supported means of reducing arterial stiffness. Reduction in arterial stiffness by n-3 may account for some of its purported cardioprotective effects.
Glycoconjugates as noninvasive probes of intrahepatic metabolism: pathways of glucose entry into compartmentalized hepatic UDP-glucose pools during glycogen accumulation. (1986)

Recent studies have questioned the efficiency with which administered glucose generates hepatic glycogen through the direct nonrecycling route compared with the indirect route from glucose recycled through glycolysis followed by gluconeogenesis. Using fasted and refed rats, we examined the relative access of infused [1-3H]- and [U-14C]glucose by way of these two pathways to liver glycogen and to hepatic glucuronic acid, the latter recovered from the urine as the glucuronide conjugated with administered acetaminophen. In fasted animals and during early refeeding, extensive dilution of administered [3H]- and [14C]glucose recovered in glycogen showed that 60-70% of the labeled glucose had undergone recycling by the indirect route. As refeeding progressed with substantial glycogen deposition, the contribution of the recycling pathway to glycogen and glucuronic acid diminished considerably. Thus, there is a shift in pathways of hepatic glucose utilization as liver glycogen accumulates. Consequently, the ratio of 3H/14C in glucuronic acid was closely correlated with the glycogen content of the liver at sacrifice, indicating that this ratio may prove useful as a noninvasive indicator of liver glycogen concentration. Since glycogen and glucuronic acid are derived by single reactions from UDP-glucose, they should show a common labeling pattern with 3H and 14C under various nutritional conditions. However, detailed analysis of their labeling patterns showed a striking divergence, implying that there must be compartmentation of the UDP-glucose pools leading to each of these end products, either because they are made in separate compartments within the same cell or because each is made in different hepatocyte populations. We favor the former explanation because galactose secreted in glycoproteins shows 3H and 14C labeling patterns similar to those of glucuronic acid conjugated with acetaminophen, and both of these conjugations occur in the endoplasmic reticulum of the liver, whereas most glycogen is present in the cytosol.
A VLSI chip set for high-speed lossless data compression (1992)

A VLSI implementation of a lossless data compression algorithm is reported. This is the first implementation of an encoder/decoder chip set that uses the Rice (see JPL Publication 91-1, 1991) algorithm and provides an introduction to the algorithm and a description of the high-performance hardware. The algorithm is adaptive over a aide entropy range. Its performance on several 8-b test images exceeds other techniques employing differential pulse code modulation (DPCM) followed by arithmetic coding, adaptive Huffman coding, and a Lempel-Ziv-Welch (LZW) algorithm. A major feature of the algorithm is that it requires no look-up tables or external RAM. There are only 71000 transistors required to implement the encoder and decoder. Each chip was fabricated in a 1.0- mu m CMOS process and both are only 5 mm on a side. A comparison is made with other hardware realizations. Under laboratory conditions, the encoder compresses at a rate in excess of 50 Msamples/s and the decoder operates at 25 Msamples/s. The current implementation processes quantized data from 4 to 14 b/sample.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Effects of dibutyryl cAMP on stanniocalcin and stanniocalcin-related protein mRNA expression in neuroblastoma cells (2002)

Stanniocalcin is a polypeptide hormone that was first reported in fish as a regulator of mineral metabolism. Its recent identification in mammals has opened a new area of investigation in basic and clinical endocrinology. In the present study, regulation of the stanniocalcin (STC) and stanniocalcin related protein (STCrP) genes were investigated in mouse neuroblastoma cells (Neuro-2A) in relation to neuronal cell differentiation. Neuro-2A is an undifferentiated cell line that contains measurable levels of STCrP mRNA, but undetectable levels of STC mRNA. Treatment of the cells with either dbcAMP (1-4 mM) or 50 microM euxanthone (PW1) resulted in extensive differentiation and neurite outgrowth. However, only neurites of dbcAMP-treated cells developed varicosities, a phenotypic marker of axon formation. Furthermore, following differentiation induced by dbcAMP, there was an upregulation of STC and downregulation of STCrP mRNA levels. In the first 24 and 48 h of treatments, there was a maximum twofold induction and 1.5-fold reduction in STC and STCrP mRNAs respectively. Following 96 h of treatment, an additional 14-fold STC induction and 1.2-fold STCrP reduction were observed. The increase in STC mRNA levels was accompanied by a concomitant increase in axon-specific low molecular form microtubule-associated protein (MAP-2c) mRNA and varicosities on the neurites, suggesting a possible role for STC in axonogenesis. There was no induction of STC mRNA levels when PW1 was added into the culture media, whereas ionomycin (1-10 microM) had no observable effects on cell differentiation or STC/STCrP mRNA. Immunocytochemical staining of dbcAMP-treated cells revealed abundant levels of immunoreactive STC, particularly in the varicosities, with only weak staining in control, untreated cells. Antisense oligodeoxynucleotides transfection studies indicated that the expression of STC was a cause of varicosity formation and a consequence of cell differentiation. Our findings lend further support to the notion that STC is involved in the process of neural differentiation.
Probing the role of loop 2 in Ras function with unnatural amino acids. (1993)

The YDPT sequence motif (residues 32-35) in loop 2 (residues 32-40) of Ha-Ras p21 protein is conserved in the Ras protein family. X-ray crystal structures have revealed significant conformational differences in this region between the GTP- and GDP-bound forms. Moreover, mutations in this region block neoplastic transformation and prevent interaction with GTPase-activating protein (GAP), suggesting that this region may contribute to the effector function of Ras. To better understand the structural features required for GAP interaction and GTPase activity, the expanded repertoire of unnatural amino acid mutagenesis has been used to investigate the roles of the key residues, Pro-34, Thr-35, and Ile-36. A Pro-34-->methanoproline mutant, in which residue 34 is locked in the trans conformation, was found to retain high levels of intrinsic and GAP-activated GTPase activity, making unlikely conformational isomerization at this position. Deletion of a single methyl group from Ile (Ile-36-->norvaline) abolished GAP activation of Ras, revealing a remarkable specificity in this protein-protein interaction. Finally, replacement of Thr-35 with diastereomeric allo-threonine led to inactivation of Ras, demonstrating the importance of the orientation of this critical residue in Ras function.
Lysosomal enzyme trafficking in mannose 6-phosphate receptor-positive mouse L-cells: demonstration of a steady state accumulation of phosphorylated acid hydrolases. (1986)

During their transport from the endoplasmic reticulum to lysosomes, newly synthesized acid hydrolases are phosphorylated in the Golgi apparatus to generate a common recognition marker, mannose 6-phosphate (Man 6-P). The phosphorylated acid hydrolases then bind to the Man 6-P receptor and are transported by an unknown route to lysosomes. To learn more about the delivery pathway, we examined the fate of the phosphorylated oligosaccharides synthesized by a Man 6-P receptor-positive line of mouse L-cells. In contrast to the rapid degradation of the recognition marker previously observed in mouse lymphoma cells (Gabel, C. A., D. E. Goldberg, and S. Kornfield. 1982. J. Cell Biol., 95:536-542), the number of high mannose oligosaccharides phosphorylated by the L-cells after a 30-min pulse labeling with [2-3H]mannose increased continuously during a subsequent 4-h chase period to a maximum of 9.3% of the total cell-associated structures. After 19 h of chase the absolute number of phosphorylated oligosaccharides declined, but the loss was accompanied by a general loss of cellular oligosaccharides such that 7.4% of the cell-associated high mannose oligosaccharides remained phosphorylated. The longevity of the Man 6-P recognition marker in the L-cells was verified by analyzing the ability of an individual acid hydrolase, beta-glucuronidase, to serve as a ligand for the Man 6-P receptor. At least 60% of the steady state beta-glucuronidase molecules isolated from the L-cells could undergo receptor-mediated endocytosis into enzyme-deficient human fibroblasts. Dense lysosomal granules isolated by metrizamide gradient centrifugation from [3H]mannose-labeled L-cells were found to be highly enriched in their content of phosphomonoester-containing oligosaccharides. The data indicate that acid hydrolases may retain their Man 6-P recognition markers within lysosomes, and suggest the possibility that dephosphorylation occurs at a nonlysosomal location through which the newly synthesized enzymes pass en route to lysosomes.
Three-Dimensional Structure Determines the Pattern of CD4+T-Cell Epitope Dominance in Influenza Virus Hemagglutinin (2007)

The structural context of a CD4(+) T-cell epitope is known to influence immunodominance at the level of antigen processing, but general rules have not emerged. Dominant epitopes of influenza virus hemagglutinin are found to be localized to the C-terminal flanks of conformationally stable segments identified by low crystallographic B-factors or high COREX residue stabilities. The bias toward C-terminal flanks is distinctive for antigens from the influenza virus. Dominant epitopes in antigens/allergens from other sources also localize to the flanks of stable segments but are found on either N- or C-terminal flanks. Thus, dominance arises from preferential endoproteolytic nicking between stable segments followed by loading of fragment terminal regions into antigen-presenting proteins. This mechanism probably arose in order to direct CD4(+) responses onto sequences that are conserved for structure and function. Structure-guided presentation could enhance protection against genetically drifting influenza virus variants but most likely reduces protection against new viral subtypes.
Monoclonal antibody targeting of liposomes to mouse lung in vivo. (1989)

A monoclonal antibody (MoAb), 273-34A, specifically binds to an epitope expressed almost exclusively on capillary endothelial cells of the lung. Within 15 min after i.v. injection, approximately 80 to 85% of the injected radioiodinated MoAb 273-34A accumulates in the lung. Approximately 90 to 95% of the recovered dose is found in the lung for up to 1 week postinjection. Ratios of MoAb 273-34A to a nonspecific, irrelevant MoAb 135-14 are 250 to 285 times higher in the lung than in the serum. When 273-34A was coupled with palmitic acid and incorporated into liposomes, the amount of 125I-labeled liposomes recovered per g of tissue was 12 times higher in the lung than in the liver at 15 min postinjection, and 22 times higher at 5 h postinjection. At 24 h postinjection the amount of liposomes per gram of lung tissue was still 6.0 times the amount per gram of liver tissue. Liposomes conjugated to MoAb 273-34A locate in the lung 20 and 15 times better than do liposomes conjugated to the nonspecific MoAb 135-14 at 15 min and 24 h postinjection, respectively. The results indicate that this immunoliposome system could be used as a model for enhanced drug delivery to the lung. The potential use for delivering anticancer drugs for therapy of lung tumors is discussed.
The structure of secondary cell wall polymers: how Gram-positive bacteria stick their cell walls together (2005)

The cell wall of Gram-positive bacteria has been a subject of detailed chemical study over the past five decades. Outside the cytoplasmic membrane of these organisms the fundamental polymer is peptidoglycan (PG), which is responsible for the maintenance of cell shape and osmotic stability. In addition, typical essential cell wall polymers such as teichoic or teichuronic acids are linked to some of the peptidoglycan chains. In this review these compounds are considered as 'classical' cell wall polymers. In the course of recent investigations of bacterial cell surface layers (S-layers) a different class of 'non-classical' secondary cell wall polymers (SCWPs) has been identified, which is involved in anchoring of S-layers to the bacterial cell surface. Comparative analyses have shown considerable differences in chemical composition, overall structure and charge behaviour of these SCWPs. This review discusses the progress that has been made in understanding the structural principles of SCWPs, which may have useful applications in S-layer-based 'supramolecular construction kits' in nanobiotechnology.
Experience with the VuNet: A network architecture for a distributed multimedia system (2002)

The VuNet is a gigabit-per-second desk/local-area asynchronous transfer mode (ATM) network built in the context of the ViewStation distributed multimedia project. The ViewStation system takes a software-intensive approach to multimedia where real-time data are processed at the application level and not in specialized hardware. The VuNet hardware is specifically designed to support this software model. The VuNet hardware and is described, and the results of experiments in which video is transported across the system are presented.
Tumor Necrosis Factor-α-stimulated Cell Proliferation Is Mediated through Sphingosine Kinase-dependent Akt Activation and Cyclin D Expression (2006)

Tumor necrosis factor-alpha (TNF-alpha) has been shown to activate sphingosine kinase (SphK) in a variety of cell types. The extent to which SphK signaling mediates the pleiotropic effects of TNF-alpha is not entirely clear. The current study examined the role of SphK activity in TNF-alpha-stimulated cell proliferation in 1321N1 glioblastoma cells. We first demonstrated that pharmacological inhibitors of SphK markedly decrease TNF-alpha-stimulated DNA synthesis. Signaling mechanisms through which SphK mediated the effect of TNF-alpha on DNA synthesis were then examined. Inhibition of Rho proteins with C3 exoenzyme or of Rho kinase with Y27632 attenuated TNF-alpha-stimulated DNA synthesis. However, RhoA activation by TNF-alpha was not blocked by SphK inhibition. ERK activation was also required for TNF-alpha-stimulated DNA synthesis but likewise TNF-alpha-induced ERK activation was not blocked by inhibition of SphK. Thus, neither RhoA nor ERK activation are the SphK-dependent transducers of TNF-alpha-induced proliferation. In contrast, TNF-alpha-stimulated Akt phosphorylation, which was also required for DNA synthesis, was attenuated by SphK inhibition or SphK1 knockdown by small interfering RNA. Furthermore, cyclin D expression was increased by TNF-alpha in a SphK- and Akt-dependent manner. Additional studies demonstrated that TNF-alpha effects on DNA synthesis, ERK, and Akt phosphorylation are not mediated through cell surface Gi -coupled S1P receptors, because none of these responses were inhibited by pertussis toxin. We conclude that SphK-dependent Akt activation plays a significant role in TNF-alpha-induced cyclin D expression and cell proliferation.
Generation and Evaluation of a Large Mutational Library from the Escherichia coli Mechanosensitive Channel of Large Conductance, MscL (2003)

Random mutagenesis of the mechanosensitive channel of large conductance (MscL) from Escherichia coli coupled with a high-throughput functional screen has provided new insights into channel structure and function. Complementary interactions of conserved residues proposed in a computational model for gating have been evaluated, and important functional regions of the channel have been identified. Mutational analysis shows that the proposed S1 helix, despite having several highly conserved residues, can be heavily mutated without significantly altering channel function. The pattern of mutations that make MscL more difficult to gate suggests that MscL senses tension with residues located near the lipid headgroups of the bilayer. The range of phenotypical changes seen has implications for a proposed model for the evolutionary origin of mechanosensitive channels.
Thermal Conversion of Hydroxy-Containing Imides to Benzoxazoles:  Polymer and Model Compound Study (1999)

A series of hydroxy-containing polyimides, containing pendent hydroxyl groups ortho to the heterocyclic imide nitrogen, were prepared via the solution condensation of aromatic dianhydrides with bisaminophenols. The polyimides were found to undergo thermal conversion to polybenzoxazoles upon heating between 350 and 500 °C under nitrogen or vacuum. The thermal conversion was accompanied by loss of carbon dioxide. No other volatile byproducts were detected by IR or NMR. Structures were confirmed by IR, solid-state NMR, and elemental analysis. Polybenzoxazole films, obtained by the thermolysis of solvent-cast poly(amic acid) or polyimide solutions, displayed excellent solvent resistance and good thermal stability. Insolubility of the polybenzoxazoles in all solvents tested indicates possible cross-linking. No crystallinity was observed by X-ray diffraction. Due to the insolubility of the resulting polybenzoxazoles, model compound reactions were also investigated. In the vapor phase at 400 °C, N-(2-hydroxyphenyl)phthalimide underwent intramolecular thermal conversion to 2-phenylbenzoxazole in 83% yield, emulating the polyimide reactions. Thermal conversion of N-(2-hydroxyphenyl)phthalimide in the melt at 400 °C resulted in the formation of intermolecular reaction products. The intermolecular reactions may be a source of possible cross-links, which would explain the insolubility of the polybenzoxazoles.
Post-translational isoprenylation of cellular proteins is altered in response to mevalonate availability (1989)

Cells incorporate isoprenoid products derived from mevalonate (MVA) into several unique proteins. The aim of this study was to delineate the effects of blocking MVA synthesis on the covalent isoprenylation of these proteins in murine erythroleukemia cells. Inhibition of protein synthesis with cycloheximide prevented the incorporation of [3H]MVA into proteins, suggesting that isoprenylation normally occurs immediately after synthesis of the polypeptides. However, incubation of cells with lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, for as little as 1 h prior to addition of cycloheximide rendered the isoprenylation step insensitive to cycloheximide. Lovastatin had no apparent effect on the stability of the isoprenylated proteins, but the development of cycloheximide insensitivity during the lovastatin preincubation was dependent on synthesis of new protein during that period. Addition of 50-200 microM MVA to the culture medium eliminated the effects of preincubation with lovastatin. Preincubation of cells with 25-hydroxycholesterol, which suppresses the synthesis and enhances the degradation of HMG-CoA reductase but is not a competitive enzyme inhibitor, did not induce cycloheximide-insensitivity of the isoprenylation reaction. The results suggest that blocking MVA synthesis with lovastatin causes a rapid depletion of isoprenoid groups available for protein modification. Consequently, there is an accumulation of non-isoprenylated substrate proteins. Shifts in the ratio of modified vs. unmodified proteins in response to MVA availability may have implications for the changes in cell morphology, cell proliferation and HMG-CoA reductase gene expression that occur when cells are subjected to MVA deprivation.
The Protein Coexpression Problem in Biotechnology and Biomedicine: Virus 2A and 2A-Like Sequences Provide a Solution (2013)

Synthetic biology enables us to create genes virtually at will. Ensuring that multiple genes are efficiently coexpressed within the same cell in order to assemble multimeric complexes, transfer biochemical pathways and transfer traits is more problematic. Viruses such as picornaviruses accomplish exactly this task: they generate multiple different proteins from a single open reading frame. The study of how foot-and-mouth disease virus controls its protein biogenesis led to the discovery of a short oligopeptide sequence, ‘2A’, that is able to mediate a cotranslational cleavage between proteins. 2A and ‘2A-like’ sequences (from other viruses and cellular sequences) can be used to concatenate multiple gene sequences into a single gene, ensuring their coexpression within the same cell. These sequences are now being used in the treatment of cancer, in the production of pluripotent stem cells, and to create transgenic plants and animals among a host of other biotechnological and biomedical applications.