gebhart/patrepeval huggingface dataset:
[Concentration of macrophage inflammatory proteins MIP-1 alpha and MIP-1 beta and interleukin 8 in erythema migrants]. (2002)

Chemokines constitute a group of proinflammatory cytokines with a strong chemotactic activity towards different populations of leukocytes. Their role in Lyme borreliosis has not been confirmed, although in vitro studies suggest possibility of chemokine synthesis during Borrelia burgdorferi infection. The aim of present study was to evaluate concentrations of chemokines: interleukin 8 (IL-8) and macrophage inflammatory protein 1 alpha and 1 beta (MIP-1 alpha and MIP-1 beta) in serum of patients with early clinical manifestation of Lyme borreliosis--erythema migrans (EM). Study group consisted of 20 patients with EM, control group of 12 healthy blood donors. Chemokine concentrations were measured with ELISA assays twice: before (examination 1) and after two weeks of antibiotic therapy (examination 2). Mean serum concentrations of IL-8, MIP-1 alpha and MIP-1 beta in examination 1 and of MIP-1 alpha and MIP-1 beta in examination 2 were significantly higher in comparison with control group. Chemokine concentrations were also significantly lower in examination 2 then in examination 1. These results show expression of IL-8, MIP-1 alpha and MIP-1 beta in the course of EM and suggest their role in the inflammatory response to Borrelia burgdorferi infection.
Oral Drug Absorption (2000)

A practical, hands-on guide for successfully developing oral drug products, this comprehensive reference runs the gamut from theoretical stages of computer-based calculations to practical guidelines for establishing in vitro/in vivo correlations. Coverage details the interrelationship between the physiology of the gastrointestinal tract and oral dr
Conversion of cysteine to formylglycine in eukaryotic sulfatases occurs by a common mechanism in the endoplasmic reticulum (1998)

Sulfatases undergo an unusual protein modification leading to conversion of a specific cysteine residue into alpha-formylglycine. This conversion is essential for catalytic activity. In arylsulfatase A the alpha-formylglycine is generated inside the endoplasmic reticulum at a late stage of protein translocation. Using in vitro translation in the presence of transport-competent microsomes we found that arylsulfatase B is also modified in a similar way by the formylglycine-generating machinery. Modification depended on protein transport and on the correct position of the relevant cysteine. Arylsulfatase A and B did not compete for modification, as became apparent in co-expression experiments. This could argue for an association of the modification machinery with the protein translocation apparatus.
Performing a check-in (2011)

Location-sharing services have a long history in research, but have only recently become available for consumers. Most popular commercial location-sharing services differ from previous research efforts in important ways: they use manual 'check-ins' to pair user location with semantically named venues rather than tracking; venues are visible to all users; location is shared with a potentially very large audience; and they employ incentives. By analysis of 20 in-depth interviews with foursquare users and 47 survey responses, we gained insight into emerging social practices surrounding location-sharing. We see a shift from privacy issues and data deluge, to more performative considerations in sharing one's location. We discuss performance aspects enabled by check-ins to public venues, and show emergent, but sometimes conflicting norms (not) to check-in.
The Ligation Systems for Ubiquitin and Ubiquitin-like Proteins (1998)

Ubiquitin (Ub) is a highly conserved small protein present universally in eukaryotic cells, which is covalently attached to substrate proteins by a cascade system, consisting of activating (E1), conjugating (E2), and/or ligating (E3) enzymes. The modification of cellular proteins with Ub targets them for degradation by a large multisubunit protease, called the 26S proteasome. The unexpected existence of many genes encoding E2 and E3 reveals that a number of distinct Ub-ligating pathways operate for selective proteolysis in cells, implying its involvement in divergent biologically important processes. Currently, it becomes clear that a set of novel molecules with a structural similarity to Ub, called Ub-like proteins (Ubls), is present in various eukaryotic cells. They are divided into two subclasses: type-1 Ubls with small sizes, such as SUMO1 and NEDD8, that are ligated to target proteins in a fashion similar, but not identical, to the ubiquitination pathway, and another type-2 Ubls that contain Ub-like structure in a variety of different classes of large proteins having apparently distinct functions, such as Rad23, Elongin B, and Parkin. Ub and type-1 Ubls are central players consisting of a new type of post-translational protein-modifying system, although the significance of type-2 Ubl remains obscure.
Phosphorylation of Nek in Response to a Variety of Receptors, Phorbol Myristate Acetate, and Cyclic AMP (1992)

The 47-kDa protein coimmunoprecipitated with phospholipase C (PLC)-gamma 1 by anti-PLC-gamma 1 monoclonal antibodies is proved to be Nck, a protein composed almost exclusively of one SH2 and three SH3 domains. Nck and PLC-gamma 1 are recognized by certain anti-PLC-gamma 1 monoclonal antibodies because Nck and PLC-gamma 1 share an epitope that likely is located in their SH3 domains. Nck is widely distributed in rat tissues, with an especially high level of expression in testes. The expression levels of Nck remains unchanged during the development of rat brain, whereas PLC-gamma 1 decreases during the same developmental period. Stimulation of A431 cells with epidermal growth factor elicits the tight association of Nck with the epidermal growth factor receptor and phosphorylation of Nck on both serine and tyrosine residues. The phosphorylation of Nck is also enhanced in response to stimulation of the nerve growth factor receptor in PC12 cells, the T-cell receptor complex in Jurkat cells, the membrane immunoglobulin M in Daudi cells, and the low-affinity immunoglobulin G receptor (Fc gamma RII) in U937 cells. The phosphorylation of Nck was also enhanced following treatment of A431 cells with phorbol 12-myristate 13-acetate or forskolin. These results suggest that Nck is a target for a variety of protein kinases that might modulate the postulated role of Nck as an adaptor for the physical and functional coordination of signalling proteins.
Muscle dysfunction in a zebrafish model of Duchenne muscular dystrophy (2016)

<i>Sapje</i> zebrafish lack the protein dystrophin and are the smallest vertebrate model of Duchenne muscular dystrophy (DMD). Their small size makes them ideal for large-scale drug discovery screens. However, the extent that <i>sapje</i> mimic the muscle dysfunction of higher vertebrate models of DMD is unclear. We used an optical birefringence assay to differentiate affected dystrophic <i>sapje</i> larvae from their unaffected siblings and then studied trunk muscle contractility at 4-7 days postfertilization. Preparation cross-sectional area (CSA) was similar for affected and unaffected larvae, yet tetanic forces of affected preparations were only 30-60% of normal. ANCOVA indicated that the linear relationship observed between tetanic force and CSA for unaffected preparations was absent in the affected population. Consequently, the average force/CSA of affected larvae was depressed 30-70%. Disproportionate reductions in twitch vs. tetanic force, and a slowing of twitch tension development and relaxation, indicated that the myofibrillar disorganization evident in the birefringence assay could not explain the entire force loss. Single eccentric contractions, in which activated preparations were lengthened 5-10%, resulted in tetanic force deficits in both groups of larvae. However, deficits of affected preparations were three- to fivefold greater at all strains and ages, even after accounting for any recovery. Based on these functional assessments, we conclude that the <i>sapje</i> mutant zebrafish is a phenotypically severe model of DMD. The severe contractile deficits of <i>sapje</i> larvae represent novel physiological endpoints for therapeutic drug screening.
Elevated intracellular levels of iron in host cells promotes Burkholderia pseudomallei infection (2012)

Background: Burkholderia pseudomallei is the causative agent of melioidosis. The disease is endemic in northeast Thailand. Several studies have reported the effect of iron-overloaded environment in promoting bacterial infection. However, little is known about the effect of host cell iron elevation on melioidosis. Objective: We investigated the impact of increased host cell iron levels on B. pseudomallei infection. Methods: HeLa and A549 cell monolayers were supplemented with ferrous sulfate (FeSO 4 ) and ascorbic acid to increase intracellular iron levels. The iron elevated host cells were infected with B. pseudomallei and examined for plaque formation, cell invasion, intracellular survival and multinucleated giant cell (MNGC) formation and compared to bacteria infecting control cells. Results: The ability of B. pseudomallei to form plaques in iron supplemented HeLa cells and to invade iron supplemented A549 cells was significantly higher. Furthermore, the intracellular survival of B. pseudomallei and the ability to induce MNGC formation in iron-supplemented host cells was greater than in infected control cells. Conclusion: Elevation of iron levels in host cells promotes B. pseudomallei infection.
G-protein-coupled receptors, cholesterol and palmitoylation: facts about fats (2009)

G-protein-coupled receptors (GPCRs) are integral membrane proteins, hence it is not surprising that a number of their structural and functional features are modulated by both proteins and lipids. The impact of interacting proteins and lipids on the assembly and signalling of GPCRs has been extensively investigated over the last 20-30 years, and a further impetus has been given by the proposal that GPCRs and/or their immediate signalling partners (G proteins) can partition within plasma membrane domains, termed rafts and caveolae, enriched in glycosphingolipids and cholesterol. The high content of these specific lipids, in particular of cholesterol, in the vicinity of GPCR transmembranes can affect GPCR structure and/or function. In addition, most GPCRs are post-translationally modified with one or more palmitic acid(s), a 16-carbon saturated fatty acid, covalently bound to cysteine(s) localised in the carboxyl-terminal cytoplasmic tail. The insertion of palmitate into the cytoplasmic leaflet of the plasma membrane can create a fourth loop, thus profoundly affecting GPCR structure and hence the interactions with intracellular partner proteins. This review briefly highlights how lipids of the membrane and the receptor themselves can influence GPCR organisation and functioning.
A phase I trial of antibody directed enzyme prodrug therapy (ADEPT) in patients with advanced colorectal carcinoma or other CEA producing tumours (2002)

Antibody-directed enzyme prodrug therapy is a targeted therapy in which a prodrug is activated selectively at the tumour site by an enzyme, which has been targeted to the tumour by an antibody (antibody-enzyme conjugate). Previous clinical trials have shown evidence of tumour response, however, the activated drug had a long half-life, which resulted in dose-limiting myelosuppression. Also, the targeting system, although giving high tumour to blood ratios of antibody-enzyme conjugate (10 000:1) required administration of a clearing antibody in addition to the antibody-enzyme conjugate. The purpose of this current study therefore was to attempt tumour targeting of the antibody-enzyme conjugate without the clearing antibody, and to investigate a new prodrug (bis-iodo phenol mustard, ZD2767P) whose activated form is highly potent and has a short half-life. Twenty-seven patients were treated with antibody-directed enzyme prodrug therapy using A5CP antibody-enzyme conjugate and ZD2767P prodrug, in a dose-escalating phase I trial. The maximum tolerated dose of ZD2767P was reached at 15.5 mg m−2 × three administrations with a serum carboxypeptidase G2 level of 0.05 U ml−1. Myelosuppression limited dose escalation. Other toxicities were mild. Patients' quality of life was not adversely affected during the trial as assessed by the measures used. There were no clinical or radiological responses seen in the study, but three patients had stable disease at day 56. Human anti-mouse antibody and human anti-carboxypeptidase G2 antibody were produced in response to the antibody enzyme conjugate (A5CP). The antibody-enzyme conjugate localisation data (carboxypeptidase G2 enzyme levels by HPLC on tumour and normal tissue samples, and gamma camera analysis of I-131 radiolabelled conjugate) are consistent with inadequate tumour localisation (median tumour: normal tissue ratios of antibody-enzyme conjugate of less than 1). A clearance system is therefore desirable with this antibody-enzyme conjugate or a more efficient targeting system is required. ZD2767P was shown to clear rapidly from the circulation and activated drug was not measurable in the blood. ZD2767P has potential for use in future antibody-directed enzyme prodrug therapy systems.
Pharmaceutically Active Natural Product Synthesis and Supply via Plant Cell Culture Technology (2008)

The chemical diversity of plant-derived natural products allows them to function in a multitude of ways including flavor enhancers, agricultural chemicals, and importantly, human medicinals. Supply of pharmaceutically active natural products is often a challenge due to the slow growing nature of some species, low yields found in nature, and unpredictable variability in accumulation. Several production options are available including natural harvestation, total chemical synthesis, semisynthesis from isolated precursors, and expression of plant pathways in microbial systems. However, for some medicinal natural products, such as the anticancer agent paclitaxel, where low yields in nature, chemical complexity and lack of knowledge of the complete biosynthetic pathway, preclude many of these options, plant cell culture technology is an attractive alternative for supply. Plant cell suspension cultures are amenable to scale-up, environmental optimization, and metabolic engineering. This review focuses on some of the key challenges in utilizing and commercializing plant cell culture suspension technology, with a focus on pharmaceutically active natural products. Recent research has been directed toward application of traditional strategies such as reactor design, cell immobilization, and enzyme elicitation as well as emerging strategies such as characterizing cellular heterogeneity and variability through flow cytometric techniques, metabolic engineering, and system-wide analysis.
JAK2V617F monitoring in polycythemia vera and essential thrombocythemia: Clinical usefulness for predicting myelofibrotic transformation and thrombotic events (2014)

The JAK2V617F allele burden has been identified as a risk factor for vascular events and myelofibrotic transformation in polycythemia vera (PV) and essential thrombocythemia (ET). However, all previous studies have evaluated a single time point JAK2V617F measurement. Therefore, the frequency and the clinical significance of changes in the JAK2V617F mutant load occurring during the disease evolution remain unknown. In the present study, JAK2V617F monitoring was performed during the follow-up of 347 patients (PV = 163, ET = 184). According to their JAK2V617F evolutionary patterns, patients were stratified as stable < 50% (n = 261), stable ≥50% (n = 52), progressive increase (n = 24) and unexplained decrease (n = 10). After a 2,453 person-years follow-up, a total of 59 thrombotic events, 16 major hemorrhages, and 27 cases of myelofibrotic transformations were registered. At multivariate analyses, patients with a persistently high (≥50%) or unsteady JAK2V617F load during follow-up had an increased risk of myelofibrotic transformation (Incidence rate ratio [IRR]: 20.7, 95% CI: 6.5-65.4; P < 0.001) and a trend for a higher incidence of thrombosis (IRR: 1.7, 1-3.3; P = 0.05) than patients with a stable allele burden below 50%. In conclusion, JAK2V617F monitoring could be useful in patients with PV and ET for predicting disease's complications, especially myelofibrotic transformation.
Retroviral targeted delivery. (1996)

The systemic delivery of genes will open new applications for gene therapy. The deployment of retroviral vectors for this purpose is being considered and requires the development of retroviral vectors with a defined target cell specificity of infection. Several reports have recently described attempts to engineer the envelope protein of murine retroviruses in order to expand the host range and enable them to infect specific human cells. The strategies are based on the introduction of binding sites specific for receptors on the surface of target cells. Although the attempts to manipulate the specificity of viral target cell recognition are ambitious and promising, they are not without pitfalls. We summarize the results obtained and the difficulties encountered.
Stabilization of cell wall proteins in Bacillus subtilis: A proteomic approach (2002)

Even though cell wall proteins of Bacillus subtilis are characterized by specific cell wall retention signals, some of these are also components of the extracellular proteome. In contrast to the majority of extracellular proteins, wall binding proteins disappeared from the extracellular proteome during the stationary phase and are subjected to proteolysis. Thus, the extracellular proteome of the multiple protease-deficient strain WB700 was analyzed which showed an increased stability of secreted WapA processing products during the stationary phase. In addition, stabilization of the WapA processing products was observed also in a sigD mutant strain which is impaired in motility and cell wall turnover. Next, we analyzed if proteins that can be extracted from B. subtilis cell walls are stabilized in the WB700 strain as well as in the sigD mutant. Thus, the cell wall proteome of B. subtilis wild type was defined showing most abundantly cell wall binding proteins (CWBPs) resulting from the WapA and WprA precursor processing. The inactivation of extracellular proteases as well as SigmaD caused an increase of CWBP105 and a decrease of CWBP62 in the cell wall proteome. We conclude that WapA processing products are substrates for the extracellular proteases which are stabilized in the absence of sigD due to an impaired cell wall turnover.
Cytochrome P-450 Involvement in the Interactions Between Plant Terpenes and Insect Herbivores (1983)

The cytochrome P-450-dependent microsomal monooxygenase system is important in several ways in insect herbivores that feed on terpene-containing plants. Cytochrome P-450 metabolises many terpenes to polar products that can be excreted, often after further conjugation reactions, or that may be more toxic to the insect. Many terpenes induce insect cytochrome P-450 to higher activity. Changes in cytochrome P-450 activity may influence hormone balance or pheromone production in the insect, implicating the plant allelochemicals as factors in the regulation of reproductive success of insect populations. Cytochrome P-450 is therefore an important factor in insect host-plant specialisations. Efforts at improving plant resistance to insect herbivory must take this enzyme system into consideration.
Keys to the Successful Application of Hydraulic Fracturing in an Emerging Coalbed Methane Prospect - An Example from the Peat Coals of Australia (2000)

Abstract Early stimulation work in Peat Field of Queensland, Australia involved application of cavity completion techniques to produce methane gas at commercial rates in the first wells completed in the reservoir gas cap. Early in the project life, cavity completion treatments resulted in promising and acceptable gas flow rates. However, excessive cost associated with this technique led to consideration of alternate stimulation approaches by the design team. The main objective was to achieve similar or better gas rates at the lowest cost. Multi-seam nitrogen-foam stimulation was conducted in several wells of the Peat field to assess the effectiveness of this technique in terms of: (1) production enhancement and cost reduction; (2) location of the coal-seam intervals in the gas cap (i..e. gas-saturated coals) and; (3) improved completion efficiency. To minimise the effects of tortuosity and multiple far-field fractures in addition to ensuring that each coal-seam interval received adequate treatment, a staged stimulation approach in combination with other remedies such as sand slugs and high injection rates was adopted and successfully applied. Zonal Isolation was achieved through the use of the newly developed, easily drillable composite plugs that allow staged treatment with flowback capabilities. Field data of representative Peat wells will be used to demonstrate the successful application of the hydraulic fracturing approach that resulted in methane gas rates that more than compete with the early cavity completion techniques either from a cost or production improvement point of view. The following specifics are addressed in the paper: A novel fracture design approach and modeling of fracturing treatments that can be of value to a broad audience of operators and design engineers.Real-time fracture stimulation methodology, analysis, and execution.Remedies to minimize the near-wellbore tortuosity and multiple far field fractures to avoid premature "screenout" and carry the fracture treatment to completion.Chemical optimization of fracture fluid designed based on coal characteristics.Use of newly developed composite epoxy-glass fracture and bridge plugs that provide a more efficient and cost effective way to carry out staged stimulation treatments.Post-fracture production tests to estimate the nitrogen- foam fracture treatment effectiveness in multi-seam CBM wells.
Strontium titanate surfaces (2007)

Strontium titanate (SrTiO 3 ) is a perovskite material with a variety of useful yet complex surface structures. Recent studies of SrTiO 3 have revealed how surface treatment can give rise to multi-functional surfaces, with attributes ranging from blue-light emission and high electrical conductivity to photocatalytic activity and nanostructure self-assembly. Research encompassing the surface science of strontium titanate is reviewed which includes studies that utilise scanning tunnelling microscopy, atomic force microscopy, electron diffraction, surface spectroscopy and theoretical modelling techniques. A series of investigations that characterise the structural and chemical environment of SrTiO 3 surfaces are outlined and discussed. Various issues regarding SrTiO 3 surfaces are examined, including near-surface chemistry, surface terminations and surface structure. Emphasis is put on the link between surface processing methods and properties. A rich variety of surface reconstructions and structures have been observed but few are well characterised. Future advances in understanding these surfaces will be accompanied by studies that apply these surfaces for engineering new systems on the nanoscale.