gebhart/patrepeval huggingface dataset:
Magnetic nanoparticles for biomedical NMR-based diagnostics (2010)

Rapid and accurate measurements of protein biomarkers, pathogens and cells in biological samples could provide useful information for early disease diagnosis, treatment monitoring, and design of personalized medicine. In general, biological samples have only negligible magnetic susceptibility. Thus, using magnetic nanoparticles for biosensing not only enhances sensitivity but also effectively reduces sample preparation needs. This review focuses on the use of magnetic nanoparticles for in vitro detection of biomolecules and cells based on magnetic resonance effects. This detection platform, termed diagnostic magnetic resonance (DMR), exploits magnetic nanoparticles as proximity sensors, which modulate the spin-spin relaxation time of water molecules surrounding molecularly-targeted nanoparticles. By developing more effective magnetic nanoparticle biosensors, DMR detection limits for various target moieties have been considerably improved over the last few years. Already, a library of magnetic nanoparticles has been developed, in which a wide range of targets, including DNA/mRNA, proteins, small molecules/drugs, bacteria, and tumor cells, have been quantified. More recently, the capabilities of DMR technology have been further advanced with new developments such as miniaturized nuclear magnetic resonance detectors, better magnetic nanoparticles and novel conjugational methods. These developments have enabled parallel and sensitive measurements to be made from small volume samples. Thus, the DMR technology is a highly attractive platform for portable, low-cost, and efficient biomolecular detection within a biomedical setting.
A functional cloning strategy, based on a binary PVX‐expression vector, to isolate HR‐inducing cDNAs of plant pathogens (2000)

We have devised a novel, high-throughput functional cloning method to isolate cDNAs from plant pathogens of which the products elicit a hypersensitive response (HR) in plants. Copy DNA, made from RNA isolated from the tomato pathogen Cladosporium fulvum grown under nutrient-limiting conditions in vitro, was cloned into a binary, potato virus X (PVX)-based expression vector and transformed to Agrobacterium tumefaciens. 9600 colonies were individually toothpick-inoculated onto leaflets of tomato plants resistant to C. fulvum. Four cDNAs were identified whose expression induced formation of a necrotic lesion around the inoculation site. One of these clones, specifically inducing HR on tomato plants carrying the Cf-4 resistance gene, encodes race-specific elicitor AVR4. The other three cDNAs, inducing a non-genotype-specific HR, encode a protein highly homologous to bZIP, basic transcription factors. To determine whether this approach has general applicability, part of the library was also inoculated onto Nicotiana tabacum var. Samsun NN, which is not a host for C. fulvum. Four independent HR-inducing cDNAs were identified which all encode ECP2, an extracellular protein of C. fulvum known to induce necrosis in certain Nicotiana species. These observations confirm that this functional screening method is a versatile strategy to identify cDNAs of pathogens that encode (race-specific) elicitors and other HR-inducing proteins.
Isolation and Expression Profiling of Genes Upregulated in the Peripheral Blood Cells of Systemic Lupus Erythematosus Patients (2005)

We have identified the genes whose expressions are augmented in the blood cells of the patients with systemic lupus erythematosus (SLE) using the 'stepwise subtraction' technique along with microarray analysis. The expression levels of these genes were assessed by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) in 31 SLE patients and 30 healthy controls. We found that the transcription levels of following eight genes were significantly increased in SLE patients; interferon (IFN)-alpha-inducible protein 27 (IFI27), IFN-alpha-inducible protein IFI-15K (G1P2), IFN stimulated gene 20 kDa (ISG20), epithelial stromal interaction 1 (EPSTI1), defensin-alpha (DEFA3), amphiregulin (AREG) and two genes of unknown function (BLAST accession nos AL050290 and AY358224 = SLED1). In comparison with idiopathic thrombocytopenic purpura (ITP), an organ-specific autoimmune disease, IFI27, G1P2 and SLED1 were preferentially upregulated in SLE. In contrast, AREG and AL050290 were more highly expressed in ITP than in SLE. We correlated changes in gene expression and clinical/laboratory features of SLE and found that expression of ISG20, EPSTI1 and SLED1 are significantly correlated with lymphocyte counts. Genes linked to IFN are well known to influence SLE, but several other novel genes unrelated to IFN signaling we report here would be useful to understand the pathophysiology of SLE.
Activation, processing and trafficking of extracellular heparanase by primary human fibroblasts (2002)

Heparanase is a heparan-sulfate-degrading endoglycosidase that has important roles in various biological processes, including angiogenesis, wound healing and metastatsis. Human heparanase is synthesized as a 65 kDa latent precursor, which is proteolytically processed into a highly active 50 kDa form. Extracellular heparanase is found in various tissues and is utilized by both normal cells and metastatic cancer cells to degrade heparan sulfate moieties in basement membranes and extracellular matrices. This study characterizes the processing and trafficking events associated with cellular activation of extracellular heparanase. We show that primary human fibroblasts are capable of binding and converting the 65 kDa heparanase precursor into its highly active 50 kDa form, concomitantly with its cytoplasmic accumulation. Heparanase uptake depends on the actin cytoskeleton integrity, resulting in a prolonged storage of the enzyme, mainly in endosomal structures. Heparanase endocytosis and its proteolytic activation are independent processes, indicating that heparanase cleavage is a cell surface event. Heparin completely inhibits heparanase endocytosis but only partially inhibits its association with the cells, suggesting that cell surface heparan sulfate moieties play a specific role in its endocytosis. Cellular binding and uptake of extracellular heparanase control its activation, clearance rate and storage within the cells.
Selection of Customized Polymers to Enhance Oil Recovery from High Temperature Reservoirs (2015)

Abstract While polymer flooding has proven to be an effective technique to improve oil recovery from mature reservoirs, the new objective pursued by the main stakeholders consists now in optimizing the overall costs and decrease the risks associated to the implementation of chemical enhanced oil recovery methods. This is particularly true for reservoir conditions with high temperatures (above 85°C) using injection brine with high hardness. In such conditions, using specific robust polymers is necessary to ensure stability over months during propagation in reservoirs. These polymers containing Acrylamido-Tert-Butyl-Sulfonate (ATBS) and N- Vinyl Pyrrolidone (NVP) are more expensive than regular HPAM and have to be overdosed to reach target viscosities since their molecular weights are low. In extreme cases, the project can be aborted for economic reasons. However, many fields, especially in South America, have access to very soft injection brines with a total dissolved salt lower than 3000 ppm in many cases. Using such brine is a tremendous advantage for polymer flooding since less robust polymers can be selected and target viscosity can be achieved with low dosages. This paper describes the selection and evaluation of polymers dedicated to high temperature reservoir conditions (from 85°C to 140°C) using very low salinity brine in comparison with harder brine. A series of rheological, shear and thermal stability tests have been performed to select the most appropriate polymer for each case. The impact of the chemical composition and the microstructure shows that the incorporation of NVP is not necessarily required to ensure stability over 6 months above 100°C in soft brines. Results show as well that ATBS improves shear and thermal stability in both soft and hard brine conditions. Besides, the incorporation of thermo-responsive moieties in the polymer improves viscosity properties resulting in a lower dosage even at high temperature to reach target viscosity. The objective of the study is also to demonstrate the possibility to develop innovative and cost-effective polymers for each reservoir condition. It encompasses an early and particularly close cooperation between the polymer manufacturer and the company willing to improve oil recovery from its reservoirs.
Simultaneous determination of glucose and galactose in dairy products by two parallel amperometric biosensors. (1999)

A sensitive, specific and rapid procedure for the simultaneous determination of glucose and galactose in dairy products based on biosensors is described. The biosensing probes consisted in two electrodes operating in parallel in a Flow Injection Analysis (FIA) system. Both electrodes consisted of a 5% rhodium-on-carbon paste, one equipped with glucose oxidase (GOX) and the other with galactose oxidase (GAOX) and peroxidase (HRP) for the determination of glucose and galactose, respectively. The rhodium-on-carbon paste electrode shows enhanced selectivity (particularly discrimination against ascorbic acid) and electro-catalysis of the reduction at lower potential of hydrogen peroxide produced by the oxidase. The response was linear from 250 to 4,000 mg L -1 with a detection limit of 45 for glucose and 98 mg L -1 for galactose. Compared with classical methods mainly based on HPLC, the proposed procedure features straightforward sample preparation and improved sensitivity and selectivity. All results reported demonstrate that the rhodium-on-carbon paste/ enzyme electrode constitutes a robust amperometric biosensor which can be used for quality control in dairy industries.
Differentiation of Human Embryonic Stem Cells to Hepatocytes Using Deleted Variant of HGF and Poly-amino-urethane-Coated Nonwoven Polytetrafluoroethylene Fabric (2006)

Human embryonic stem (hES) cells have recently been studied as an attractive source for the development of a bioartificial liver (BAL). Here we evaluate the differentiation capacity of hES cells into hepatocytes. hES cells were subjected to suspension culture for 5 days, and then cultured onto poly-amino-urethane (PAU)-coated, nonwoven polytetrafluoroethylene (PTFE) fabric in the presence of fibroblast growth factor-2 (bFGF) (100 ng/ml) for 3 days, then with deleted variant of hepatocyte growth factor (dHGF) (100 ng/ml) and 1% dimethyl sulfoxide (DMSO) for 8 days, and finally with dexamethasone (10(-7) M) for 3 days. The hES cells showed gene expression of albumin in a time-dependent manner of the hepatic differentiation process. The resultant hES-derived hepatocytes metabolized the loaded ammonia and lidocaine at 7.8% and 23.6%, respectively. A million of such hepatocytes produced albumin and urea at 351.2 ng and urea at 7.0 microg. Scanning electron microscopy showed good attachment of the cells on the surface of the PTFE fabric and well-developed glycogen rosettes and Gap junction. In the present work we have demonstrated the efficient differentiation of hES cells to functional hepatocytes. The findings are useful to develop a BAL.
Calcimimetics with potent and selective activity on the parathyroid calcium receptor (1998)

Parathyroid hormone (PTH) secretion is regulated by a cell surface Ca2+ receptor that detects small changes in the level of plasma Ca2+. Because this G protein-coupled receptor conceivably provides a distinct molecular target for drugs useful in treating bone and mineral-related disorders, we sought to design small organic molecules that act on the Ca2+ receptor. We discovered that certain phenylalkylamine compounds, typified by NPS R-568 and its deschloro derivative NPS R-467, increased the concentration of cytoplasmic Ca2+ ([Ca2+]i) in bovine parathyroid cells and inhibited PTH secretion at nanomolar concentrations. These effects were stereoselective and the R enantiomers were 10- to 100-fold more potent than the S enantiomers. NPS R-568 potentiated the effects of extracellular Ca2+ on [Ca2+]i and PTH secretion but was without effect in the absence of extracellular Ca2+. Both compounds shifted the concentration-response curves for extracellular Ca2+ to the left. Presumably, these compounds act as positive allosteric modulators to increase the sensitivity of the Ca2+ receptor to activation by extracellular Ca2+. Both NPS R-467 and NPS R-568 increased [Ca2+]i in HEK 293 cells expressing the human parathyroid Ca2+ receptor but were without effect in wild-type HEK 293 cells. Neither compound affected the cytoplasmic Ca2+ responses elicited by several other G protein-coupled receptors in HEK 293 cells or in bovine parathyroid cells. Significantly, these compounds did not affect responses elicited by the homologous metabotropic glutamate receptors, mGluR1a, mGluR2, or mGluR8. These compounds therefore act selectively on the Ca2+ receptor. Compounds that mimic or potentiate the effects of extracellular Ca2+ at the Ca2+ receptor are termed calcimimetics. The discovery of calcimimetic compounds with potent and selective activity enables a pharmacological approach to regulating plasma levels of PTH. Calcimimetic compounds could conceivably provide a specific medical therapy for primary hyperparathyroidism.
Protein Structure-Based Drug Design (1994)

Design cycles will undoubtedly play an increasingly important role in drug discovery in the coming years, as the amount of structural information on protein targets continues to rise. However, the traditional method of drug discovery, based upon random screening and systematic modification of leads by medicinal chemistry techniques, will probably not be abandoned completely because it has a potentially important advantage over more structure-based methods--namely, leads identified in this way are unlikely to show a close resemblance to the natural ligand or substrate. They may, therefore, have advantages in terms of patent novelty, selectivity, or pharmacokinetic profile. However, such leads could then serve as the basis for structure-based, rational modification programs, in which their interactions with target receptors are defined (as we have described) and improved molecules are designed. A final important point to be made about structure-based design in drug discovery is that, while it can be of great use in the initial process of identifying ligands with improved affinity and selectivity in vitro, it can usually say very little about other essential aspects of the drug discovery process, e.g. the need to achieve an adequate pharmacokinetic profile and low toxicity in vivo. This observation reminds us that drug design is a multidisciplinary process, involving molecular biologists, biochemists, pharmacologists, organic chemists, crystallographers, and others. In order to be effective, therefore, structure-based design must be properly integrated into the overall discovery effort.
Long-acting pegylated human GH in children with GH deficiency: a single-dose, dose-escalation trial investigating safety, tolerability, pharmacokinetics and pharmacodynamics (2011)

Single doses of long-acting NNC126-0083 were safe and well tolerated in children with GHD. Increased IGF1 levels were observed in all NNC126-0083 dose groups; however, a satisfactory once-weekly IGF1 profile was not reached within the NNC126-0083 dose levels administered.
Laboratory evaluation of the inflammatory myopathies (1995)

The laboratory plays an important role in the diagnosis, evaluation, and classification of the heterogeneous group of diseases known as the IIM, which are characterized by chronic muscle inflammation. Serial measurements of the levels of muscle-derived enzymes in serum are the traditional laboratory studies used to follow the clinical course of patients with IIM, although other laboratory tests can also be useful in assessing myositis disease activity. Several markers of immune system activation, including cytokines and lymphocyte markers, show promise as possibly more sensitive measures of myositis disease activity. Discovery of a unique group of MSAs over the past decade has provided an immunologic basis for defining relatively homogeneous subsets of patients who share similar clinical features, disease courses, and responses to therapy. Future investigations of novel immunologic activation markers, as well as the cloning and expression of target autoantigens of the MSAs, should allow better diagnostic assays, enhanced prognosis, and a better understanding of the pathogenesis of these disorders.
Use of monoclonal antibodies to study alloreactivity and T cell development in Xenopus (1993)

This study investigated T-cell surface antigenic changes in the spleen of Xenopus following in vivo and in vitro allergenic challenge, using novel mouse monoclonal antibodies (mAb's) against all T cells (CDS), the putative ÉÎ²-T cell receptor (TCR), the putative Î³Î´-TCR, the CD8 receptor and against major histocompatibility complex (MHC) class II proteins. Flow cytometric analyses of splenocytes from skin allografted intact, 5-day thymectomised (Tx) and skin allotolerant animals were examined. There was an increase in the number of cells expressing Î³Î´ TCR's in those froges which rejected test allografts. The Tx Xenopus laevis and allotolerant LG3 animals that tolerated grafts showed no increase in the 76 TCR. Twenty-four days post-grafting X. laevis, most of the Î³Î´ TCR positive cells surprisingly co-expressed the ÉÎ² TCR. Following mixed lymphocyte reactions (MLR) for 9-14 days, of previously grafted X. laevis and LG15 splenocytes, there was an increase in the number of T cells with a significant increase Î³Î´-TCR positive cells. Stimulation indices of MLR's were increased by pre-culturing the stimulator cells with concanavalin A (ConA). This increase was apparently not due to changes in cytokine production or cell surface antigen expression, of the stimulated cells. Little increased MHC class II expression was seen, in flow cytometric analyses. The reasons for elevated MLR with ConA-activated stimulators therefore remain to be assessed. The in vitro response of Xenopus splenocytes to the superantigen, staphylococcal enterotoxin B (SEB), was tested. The response was weakly significant but was significantly less than that seen in mice.
Selective Efficacy of Depsipeptide in a Xenograft Model of Epstein-Barr Virus-Positive Lymphoproliferative Disorder (2004)

Apoptosis is induced by depsipeptide via caspase-dependent and -independent pathways in Lat-III EBV-positive LCLs and is enhanced by inhibiting NF-kappaB activity. Depsipeptide as a treatment for Lat-III EBV-associated lymphoproliferative disorders should be explored further in clinical trials.
Re-evaluation of the fructosamine reaction. (1988)

The difference in spectral characteristics between 1-deoxy-1-morpholinofructose (DMF) and protein/plasma samples in the fructosamine reaction has been related to the solubility of the diformazan formed by reduction of nitro blue tetrazolium chloride. Addition of the surfactant Triton X-100 (20 g/L) to the reagent buffer not only corrects this anomaly but also enhances the absolute response. Detailed investigation of DMF and dihydroxyacetone as calibration standards for the reaction established a clear preference for the latter. Fundamental differences in reaction kinetics were also noted between the Amadori rearrangement products of glucose formed from morpholine (DMF) or the amino lysine groups of protein (glycated albumin). From the reactivity of dihydroxyacetone, as well as glyceraldehyde, observed in the fructosamine reaction, and the presence of this class of compounds (trioses) in human plasma, we infer that they may also contribute to the differentiation of diabetic and non-diabetic samples.
Immortalized Dopamine Neurons: A Model to Study Neurotoxicity and Neuroprotection (1999)

6-Hydroxydopamine (6-OHDA) causes selective degeneration of dopaminergic neurons in the rat brain and has been used to produce an animal model of Parkinsonism. Recently, a clonal line of immortalized dopamine (DA) neurons (1RB3AN27), which expresses varying levels of tyrosine hydroxylase, dopamine transporter, neuron specific enolase, and nestin, was established. These DA neurons reduce behavioral deficits in 6-OHDA-lesioned rats. The relative sensitivity of fetal and adult neurons to potential neurotoxins is not well defined. The availability of immortalized DA neurons provides a unique opportunity to compare the relative neurotoxicity of 6-OHDA in differentiated and undifferentiated DA neurons in vitro and identify neuroprotective agents. Our results showed that 6-OHDA treatment for 24 hr decreased the viability of undifferentiated and differentiated immortalized DA neurons in vitro, as determined by the MTT assay, and increased the rate of apoptosis in differentiated DA neurons. The differentiated DA neurons (IC50 = 33 microM) were about 2-fold more sensitive to 6-OHDA than undifferentiated DA neurons (IC50 = 75 microM) in cell culture. Similarly, the differentiated DA neurons were more sensitive to another neurotoxin, 1-methyl-4-phenylpyridinium (MPP+), which is commonly used to induce Parkinsonism in animal models, than were the undifferentiated DA neurons in culture. Among growth factors tested, only glial cell line-derived neurotrophic factor (GDNF) partially protected differentiated DA neurons against 6-OHDA-induced toxicity. These results suggest that undifferentiated and differentiated immortalized DA neurons can be a useful experimental model to study relative sensitivity to neurotoxins and neuroprotective agents that could have relevance to fetal and adult neurons.