gebhart/patrepeval huggingface dataset:
Adeno-associated virus vectors preferentially transduce cells in S phase. (1994)

Vectors based on adeno-associated virus can stably transfer genes by chromosomal integration in recipient cells. In this study we have infected stationary and dividing primary human fibroblast cultures with adeno-associated virus vectors encoding alkaline phosphatase and neomycin phosphotransferase. We find that the transduction frequency of S phase cells is about 200 times that of non-S phase cells. However, neither S phase nor mitosis is essential for transduction. Single-stranded vector genomes survive in stationary cultures and can be recruited for transduction by stimulating these cultures to divide. Stable transductants contain randomly integrated vector sequences. These findings have important implications for the use of adeno-associated virus vectors in gene therapy.
Purification and characterization of an enzyme releasing lacto-N-biose from oligosaccharides with type 1 chain. (1993)

An enzyme specific for oligosaccharides with type 1 chain was purified 7,000-fold from the culture broth of Streptomyces sp. 142. The enzyme, lacto-N-biosidase, was induced and secreted into culture medium when the strain was cultured in the presence of porcine stomach mucin. The enzyme was purified by anion-exchange chromatography on Q Sepharose, cation-exchange chromatography on S Sepharose, fast protein liquid chromatography on a Mono S column, and gel filtration chromatography on TSK gel HW55S. To remove contaminating alpha-1,3/4-fucosidase and beta-N-acetylglucosaminidase, final purification was done by fast protein liquid chromatography on a Mono S column and affinity chromatography on N-acetylglucosamine agarose. The purified enzyme gave only one major protein band with an apparent M(r) of 60,000 on sodium dodesyl sulfate-polyacrylamide gel electrophoresis. The enzyme had maximum activity at pH 5.5 and was stable at the pH range of 4.0-10.0. Substrate specificity studies with oligosaccharides labeled with 2-aminopyridine showed that the enzyme specifically hydrolyzed lacto-N-tetraose and the N-acetyllactosamine type of triantennary sugar chain with the type 1 chain, but did not hydrolyze type 2 chain oligosaccharides or the type 1 chain oligosaccharides with fucose or sialic acid including lacto-N-fucopentaose I and II and alpha-2,3-sialyl lacto-N-tetraose. The enzyme released lacto-N-biose from asialofetuin, and almost all oligosaccharides in asialofetuin were found to have only type 2 chains. Sequential digestion of extended type 1 chain oligosaccharides with alpha-1,3/4-fucosidase and lacto-N-biosidase was possible.
Isolation and characterization of eight tumor necrosis factor-induced gene sequences from human fibroblasts. (1990)

A lambda cDNA library was prepared from polyadenylated RNA isolated from quiescent human diploid FS-4 fibroblasts stimulated with tumor necrosis factor for 3 h. Differential screening was used to isolate cDNA sequences that are stimulated by tumor necrosis factor. Eight distinct tumor necrosis factor-stimulated gene sequences (designated TSG-1, -6, -8, -12, -14, -21, -27, and -37) were partially sequenced and compared with known sequences from GenBank. TSG-1 was identical to the gene for interleukin-8. TSG-8 corresponded to the gene for monocyte chemotactic and activating factor. TSG-21 and -27 were identical to the genes for collagenase and stromelysin, respectively. The other four sequences showed no homologies with known genes. Patterns of induction of mRNAs corresponding to the eight cloned cDNAs by various cytokines, growth factors, and activators of second messenger pathways were analyzed in FS-4 cells.
Expression and Characterization of Human CD4: Immunoglobulin Fusion Proteins (1990)

Different chimeric antibody-like molecules consisting of the four human CD4 extracellular domains (amino acids 1-369) fused to different parts of human IgG1 and IgM heavy-chain constant regions have been created and expressed in mammalian cells. For both IgG1 and IgM fusion proteins, the best expression in COS cells was observed for molecules lacking the CH1 domain of the heavy-chain constant region. The chimeric molecules are potent inhibitors of human immunodeficiency virus (HIV) infection and HIV-mediated cytotoxicity. A CD4:IgG1 hinge fusion protein, which was analyzed in more detail, binds efficiently to HIV gp160 and human Fc receptors and shows complement-assisted inhibition of viral propagation in culture. Half-life studies after intravenous application of the latter human fusion protein into mice and monkeys showed significant prolongation of serum survival compared to soluble CD4. An IgG2b murine homolog of the human CD4:IgG1 hinge fusion protein was prepared and evaluated in mice, where it was found to be nontoxic and to have no detectable effect on the humoral response to soluble antigen.
MutS HOMOLOG1-Derived Epigenetic Breeding Potential in Tomato (2015)

Evidence is compelling in support of a naturally occurring epigenetic influence on phenotype expression in land plants, although discerning the epigenetic contribution is difficult. Agriculturally important attributes like heterosis, inbreeding depression, phenotypic plasticity, and environmental stress response are thought to have significant epigenetic components, but unequivocal demonstration of this is often infeasible. Here, we investigate gene silencing of a single nuclear gene, MutS HOMOLOG1 (MSH1), in the tomato (Solanum lycopersicum) 'Rutgers' to effect developmental reprogramming of the plant. The condition is heritable in subsequent generations independent of the MSH1-RNA interference transgene. Crossing these transgene-null, developmentally altered plants to the isogenic cv Rutgers wild type results in progeny lines that show enhanced, heritable growth vigor under both greenhouse and field conditions. This boosted vigor appears to be graft transmissible and is partially reversed by treatment with the methylation inhibitor 5-azacytidine, implying the influence of mobile, epigenetic factors and DNA methylation changes. These data provide compelling evidence for the feasibility of epigenetic breeding in a crop plant.
The human immunodeficiency virus type 1 packaging signal and major splice donor region have a conserved stable secondary structure (1992)

Interaction of cis-acting RNA sequences with nucleocapsid proteins is one of the critical events leading to retroviral genomic RNA packaging. We have derived a potentially stable secondary structure for the packaging signal region of human immunodeficiency virus strain IIIB, using a combination of biochemical analysis and computer modelling. This region encompasses the major splice donor (SD), which is found in a highly structured conserved stem-loop. Comparison with other published human immunodeficiency virus type 1 sequences shows almost absolute nucleotide conservation in base-paired regions required to maintain this structure. Presently and previously described packaging-defective mutants would disrupt the structure. The structure depends on base pairing between nucleotide sequences 5' of the major SD which are common to both genomic and subgenomic RNAs and sequences 3' of SD which are unique to the unspliced RNA. This may explain how in retroviruses such as Rous sarcoma virus, mutations in regions common to genomic and subgenomic RNA might prevent packaging of the unspliced mRNA by disrupting a signal structure which can exist only in the genomic RNA species.
Activation of nuclear factor kappa B and cytokine imbalance in experimental alcoholic liver disease in the rat (1999)

Inflammatory stimuli and lipid peroxidation activate nuclear factor kappa B (NF-kappaB) and upregulate proinflammatory cytokines and chemokines. The present study evaluated the relationship between pathological liver injury, endotoxemia, lipid peroxidation, and NF-kappaB activation and imbalance between pro- and anti-inflammatory cytokines. Rats (5 per group) were fed ethanol and a diet containing saturated fat, palm oil, corn oil, or fish oil by intragastric infusion. Dextrose isocalorically replaced ethanol in control rats. Pathological analysis was performed and measurements of endotoxin were taken, lipid peroxidation, NF-kappaB, and messenger RNA (mRNA) levels of proinflammatory cytokines (tumor necrosis factor-alpha [TNFalpha], interleukin-1 beta [IL-1beta], interferon-gamma, [IFN-gamma], and IL-12), C-C chemokines (regulated upon activation, normal T cell expressed and secreted [RANTES], monocyte chemotactic protein [MCP]-1, macrophage inflammatory protein [MIP]-1alpha), C-X-C chemokines (cytokine induced neutrophil chemoattractant (CINC), MIP-2, IP-10, and epithelial neutrophil activating protein [ENA]-78), and anti-inflammatory cytokines (IL-10, IL-4, and IL-13). Activation of NF-kappaB and increased expression of proinflammatory cytokines C-C and C-X-C chemokines was seen in the rats exhibiting necroinflammatory injury (fish oil-ethanol [FE] and corn oil-ethanol[CE]). These groups also had the highest levels of endotoxin and lipid peroxidation. Levels of IL-10 and IL-4 mRNA were lower in the group exhibiting inflammatory liver injury. Thus, activation of NF-kappaB occurs in the presence of proinflammatory stimuli and results in increased expression of proinflammatory cytokines and chemokines. The Kupffer cell is probably the major cell type showing activation of NF-kappaB although the contribution of endothelial cells and hepatocytes cannot be excluded. Downregulation of anti-inflammatory cytokines may additionally exacerbate liver injury.
Efficient Ether Cleavage in Lignins: The Derivatization Followed by Reductive Cleavage Procedure as a Basis for New Analytical Methods (1998)

A new method is introduced for cleaving α- and β-alkyl ethers in lignins. Acetyl bromide treatment dissolves the lignin or whole cell wall material, cleaving benzyl aryl ethers, acetylating primary hydroxyl groups, and brominating benzylic positions. The key step is reductive cleavage of the resulting α-bromo-β-ethers to give cinnamyl acetates. Finally, the product is acetylated to minimize the number of components and to facilitate GC separation. The method has been named the 'DFRC' procedure, an acronym for the methodology involved (Derivatization Followed by Reductive Cleavage). Low molecular mass products can be extracted from the crude mixture; GC analysis gives data similar to those from analytical thioacidolysis. The basic method itself can be adapted for numerous other analytical determinations of value to lignin researchers.
Therapy Options in Imatinib Failures (2008)

Chronic myelogenous leukemia (CML) is defined by the presence of the constitutively active tyrosine kinase breakpoint cluster region/Abelson (Bcr-Abl), which activates numerous signal transduction pathways leading to uncontrolled cell proliferation. The development of the Bcr-Abl-targeted imatinib represents a paradigm shift in the treatment of CML, because treatment with imatinib resulted in significantly better patient outcome, response rates, and overall survival compared with previous standards. Despite this advance, not all patients benefit from imatinib because of resistance and intolerance. Resistance to imatinib can develop from a number of mechanisms that can be defined as Bcr-Abl-dependent (e.g., most commonly resulting from point mutations in the Abl kinase domain) and Bcr-Abl-independent mechanisms (including the constitutive activation of downstream signaling molecules, e.g., Src family kinases), which could result in the activation of the pathway regardless of Bcr-Abl inhibition. Clearly, new treatment approaches are required for patients resistant to or intolerant of imatinib, which can be dose escalated in patients who demonstrate resistance. This does not result in long-term responses. Hematopoietic stem cell transplantation is limited by the availability of matched donors and the potential for morbidity. Dasatinib, a dual Bcr-Abl/Src kinase inhibitor, has shown efficacy against all imatinib-resistant Bcr-Abl mutations except for T315I. A large trial program showed that dasatinib is effective in patients previously exposed to imatinib and has a manageable safety profile in all phases of CML and Philadelphia chromosome-positive acute lymphoblastic leukemia, resulting in its approval. Nilotinib, an analogue of imatinib, also has demonstrated activity in a similar patient population. These agents and less clinically advanced strategies are discussed in this review.
HEVC Lossless Coding and Improvements (2012)

The lossless coding mode of the High Efficiency Video Coding (HEVC) main profile that bypasses transform, quantization, and in-loop filters is described. Compared to the HEVC nonlossless coding mode with the smallest quantization parameter value (i.e., 0 for 8-b video and -12 for 10-b video), the HEVC lossless coding mode provides perfect fidelity and an average bit-rate reduction of 3.2%-13.2%. It also significantly outperforms the existing lossless compression solutions, such as JPEG2000 and JPEG-LS for images as well as 7-Zip and WinRAR for data archiving. To further improve the coding efficiency of the HEVC lossless mode, a sample-based angular intra prediction (SAP) method is presented. The SAP employs the same prediction mode signaling method and the sample interpolation method as the HEVC block-based angular prediction, but uses adjacent neighbors for better intra prediction accuracy and performs prediction sample by sample. The experimental results reveal that the SAP provides an additional bit-rate reduction of 1.8%-11.8% on top of the HEVC lossless coding mode.
Bottom-up and top-down neuromorphic processor design : Unveiling roads to embedded cognition (2020)

While Moore's law has driven exponential computing power expectations, its nearing end calls for new roads to embedded cognition. The field of neuromorphic computing aims at a two-fold paradigm shift compared to conventional computing. First, it investigates the co-location of processing and memory in neurons and synapses. Second, it aims at encoding data both in space and time with all-or-none spike events. However, it is unclear which of the bottom-up (neuroscience-driven) or top-down (application-driven) design approaches could unveil the most promising roads to embedded cognition. In order to clarify this question, this thesis is divided into two parts. The first part focuses on the bottom-up approach. From the building-block level to the silicon integration, we design two bottom-up neuromorphic processors: ODIN and MorphIC. We demonstrate with measurement results that hardware-aware neuroscience model design and selection allows reaching record neuron and synapse densities with low-power operation. However, the inherent difficulty for bottom-up designs lies in applying them to real-world problems beyond the scope of neuroscience applications. The second part investigates the top-down approach. By starting from the applicative problem of adaptive edge computing, we derive the direct random target projection (DRTP) algorithm for low-cost neural network training and design a top-down DRTP-enabled neuromorphic processor: SPOON. We demonstrate with pre-silicon implementation results that combining event-driven and frame-based processing with weight-transport-free update-unlocked training supports low-cost adaptive edge computing with spike-based sensors. However, defining a suitable target for bio-inspiration in top-down designs is difficult, as it should ensure both the efficiency and the relevance of the resulting neuromorphic devices. Therefore, we claim that each of these two design approaches can act as a guide to address the shortcomings of the other.
Protein Cross-linking by the Maillard Reaction (1996)

The Maillard reaction, initiated by nonenzymatic glycosylation of amino groups on proteins by reducing sugars, has been studied for its potential role in aging and the complications of diabetes. One of the major consequences of the advanced Maillard reaction in proteins is the formation of covalently cross-linked aggregates. The chemical nature of the cross-linking structures is largely unknown. Recently, methylglyoxal has been shown to be a potential glycating agent in vivo and suggested to be a common intermediate in the Maillard reaction involving glucose. Methylglyoxal can form enzymatically or nonenzymatically from glycolytic intermediates and by retro-aldol cleavage of sugars. Its elevation in tissues in diabetes and its high potency to glycate and cross-link proteins led us to investigate the chemical nature of its advanced Maillard products. Using an approach in which a synthetic model peptide was reacted with methylglyoxal, we isolated and purified a cross-linked peptide dimer. Characterization of this dimer revealed that the peptides are linked through epsilon amino groups of lysine residues. The actual cross-link was shown to be a methylimidazolium, formed from the reaction of two lysines and two methylglyoxal molecules. We have named this cross-link imidazolysine. Imidazolysine was detected in proteins by high performance liquid chromatography using a postcolumn derivatization method. Proteins incubated with methylglyoxal showed a time-dependent formation of imidazolysine. Quantification of imidazolysine in human serum proteins revealed a significant increase (p < 0.05) in diabetic samples (mean +/- S.D., 313.8 +/- 52.7 pmol/mg protein) when compared with normal samples (261.3 +/- 50.4). These values correlated with glycohemoglobin (p < 0.05). These results provide chemical evidence for protein cross-linking by dicarbonyl compounds in vivo.
Identification of human nephron progenitors capable of generation of kidney structures and functional repair of chronic renal disease (2013)

Identification of tissue-specific renal stem/progenitor cells with nephrogenic potential is a critical step in developing cell-based therapies for renal disease. In the human kidney, stem/progenitor cells are induced into the nephrogenic pathway to form nephrons until the 34 week of gestation, and no equivalent cell types can be traced in the adult kidney. Human nephron progenitor cells (hNPCs) have yet to be isolated. Here we show that growth of human foetal kidneys in serum-free defined conditions and prospective isolation of NCAM1(+) cells selects for nephron lineage that includes the SIX2-positive cap mesenchyme cells identifying a mitotically active population with in vitro clonogenic and stem/progenitor properties. After transplantation in the chick embryo, these cells-but not differentiated counterparts-efficiently formed various nephron tubule types. hNPCs engrafted and integrated in diseased murine kidneys and treatment of renal failure in the 5/6 nephrectomy kidney injury model had beneficial effects on renal function halting disease progression. These findings constitute the first definition of an intrinsic nephron precursor population, with major potential for cell-based therapeutic strategies and modelling of kidney disease.
Communications Systems Based on Chaos (2007)

Tesis Doctoral leida en la Universidad Rey Juan Carlos en 2007. Directores de la Tesis: Miguel Angel Fernandez Sanjuan y Luis Lopez Fernandez
Hypercholesterolemia With Cholesterol-Enriched LDL and Normal Levels of LDL–Apolipoprotein B (1996)

One form of hypercholesterolemia is characterized by high levels of LDL cholesterol and normal levels of LDL-apolipoprotein (apo) B. The reason for hypercholesterolemia, therefore, is enrichment of LDL particles with cholesterol. We have reported previously that about one third of patients with primary moderate hypercholesterolemia have this lipoprotein pattern and have no apparent abnormality in LDL-apo B metabolism. The current study was designed to determine whether the combination of the Step I Diet (30% of total calories as fat, <10% saturated fatty acids, and <300 mg per day cholesterol) with or without cholestyramine therapy will correct the hypercholesterolemia in patients of this type. Ten hypercholesterolemic men of this type were identified and recruited into the study. Their LDL cholesterol levels were > or = 160 mg/dL and LDL-apo B levels were <120 mg/dL (LDL cholesterol/apo B ratio >1.60). For patient selection, subjects were challenged with a high fat diet (40% of total calories as fat, 18% saturated fatty acids, and 400 mg per day cholesterol) for 6 weeks to confirm persistence of a high LDL cholesterol/apo B ratio. Thereafter, they were started on a Step I Diet, and lipoprotein analyses were repeated. Finally, cholestyramine (16 g per day) was added to the Step I Diet. The Step I Diet alone significantly reduced the LDL cholesterol/apo B ratios and produced a trend toward lowering LDL cholesterol levels. Cholestyramine therapy further reduced LDL cholesterol levels and maintained a normal LDL cholesterol/apo B ratio. The present investigation thus confirms the existence of a form of moderate hypercholesterolemia that arises from a defect in LDL composition. In addition, it demonstrates that the combination of Step I Diet and cholestyramine therapy corrects this defect and normalizes LDL levels and LDL composition.
Glucose modulates hemodynamic, metabolic, and inflammatory responses to lipopolysaccharide in rabbits (1997)

Glucose is important for vascular and immunocompetent cell functions. We hypothesized that modifications in glucose metabolism (normal feeding, 24-h fasting, glucose loading) may influence the hemodynamic, metabolic, and inflammatory responses to lipopolysaccharide administration (LPS; 600 micrograms/kg iv) in rabbits. Aortic (ABFV), hepatic artery (HABFV), and portal vein blood flow velocities (PVBFV) (pulsed Doppler), plasma tumor necrosis factor (TNF) and nitrites were measured. Fasting depleted hepatic glycogen content, and intraportal glucose load (2 g/kg) partially restored it. LPS induced a similar hypotension (-20%, P < 0.05) in three groups of animals. In fed animals, systemic vasoconstriction occurred with low ABFV and PVBFV (-40%, P < 0.05), together with lactacidemia and hyperglycemia. In fasted animals, ABFV and PVBFV were maintained, without metabolic acidosis or hyperglycemia. Glucose loading induced hemodynamic and metabolic patterns comparable to those observed in fed animals, although significantly more severe. TNF release was amplified fourfold by glucose loading, with no impact on nitrite levels. In conclusion, glucose metabolism interferes with hemodynamic, metabolic, and inflammatory responses to LPS.
Structure, regulation and cellular functions of Rab geranylgeranyl transferase and its cellular partner Rab Escort Protein (2012)

Rab geranylgeranyl transferase is an enzyme responsible for double geranylgeranylation of Rab proteins in all eukaryotic cells. In the present article we would like to focus on new findings concerning the holoenzyme structure and mechanism of catalytic activity, its mode of regulation and consequences of RGGT deficiency in different eucaryotic model organisms and patients.
Cutting Edge: Naive T Cells Masquerading as Memory Cells (2000)

This study shows that naive CD8 T cells can acquire characteristics of memory T cells in the absence of stimulation with specific Ag simply by the process of homeostatic proliferation under lymphopenic conditions. This Ag-independent T cell differentiation pathway did not result in up-regulation of early activation markers (CD69, CD25, CD71), but expression of several memory markers (CD44, CD122, Ly6C) increased progressively with successive divisions. These markers were then stably expressed, and these cells also became more responsive functionally to specific Ag. Thus, all "memory" phenotype T cells in an individual may not be true Ag-experienced cells and may include naive cells masquerading as memory cells. These findings are specially relevant in cases of disease or treatment-induced lymphopenia such as in HIV-infected individuals or transplant recipients. In addition, this study may have implications for autoimmunity because homeostatic proliferation of naive T cells requires interaction with self peptide plus MHC molecules.