gebhart/patrepeval huggingface dataset:
Therapeutic efficacy of a polymyxin B-dextran 70 conjugate in experimental model of endotoxemia (1995)

Numerous studies have suggested that lipopolysaccharide (LPS), a major component of the cell wall of gram-negative bacteria, is responsible for the initiation of gram-negative septic shock. Previously, others have designed therapeutic regimens to target the biologically active lipid A region of LPS by either neutralization of the biological properties of LPS or enhancement of clearance of this molecule. One such compound capable of neutralizing lipid A is the antibiotic polymyxin B. However, the clinical utility of polymyxin B is limited by its toxicity. We therefore covalently conjugated this antibiotic to the high-molecular-weight polysaccharide dextran 70, resulting in reduced toxicity of polymyxin B but retention of its endotoxin-neutralizing ability. The studies described in this report were designed to test the in vivo efficacy of this compound in an experimental animal model of gram-negative septic shock. Mice were administered graded doses of Escherichia coli or Pseudomonas aeruginosa along with D-galactosamine and the antibiotic imipenem. We had previously determined that antibiotic chemotherapy provides significant protection against E. coli-mediated lethality with smaller doses of bacteria; however, the antibiotic does not provide protection against larger doses of bacteria, but it is effective at killing the bacterial inoculum in vivo. Administration of the polymyxin B-dextran 70 conjugate provided significant protection when given with an antibiotic but was not effective by itself. A requirement for a pretreatment period prior to E. coli challenge was shown to depend upon the bacterial challenge dose. In other studies using this D-galactosamine sensitization model, we demonstrated that the lipid A-specific conjugate had no effect on lethality caused by staphylococcus aureus or tumor necrosis factor alpha. The results of these studies indicate that this compound is effective in preventing lethal gram-negative septic shock in mice and may be useful as a potential therapeutic agent in humans as well.
Activation of Human Immunodeficiency Virus Transcription in T Cells Revisited: NF-κB p65 Stimulates Transcriptional Elongation (2001)

Human immunodeficiency virus type 1 (HIV-1) is able to establish a persistent latent infection during which the integrated provirus remains transcriptionally silent. Viral transcription is stimulated by NF-kappaB, which is activated following the exposure of infected T cells to antigens or mitogens. Although it is commonly assumed that NF-kappaB stimulates transcriptional initiation alone, we have found using RNase protection assays that, in addition to stimulating initiation, it can also stimulate elongation from the HIV-1 long terminal repeat. When either Jurkat or CCRF/CEM cells were activated by the mitogens phorbol myristate acetate and phytohemagglutinin, elongation, as measured by the proportion of full-length transcripts, increased two- to fourfold, even in the absence of Tat. Transfection of T cells with plasmids carrying the different subunits of NF-kappaB demonstrated that the activation of transcriptional elongation is mediated specifically by the p65 subunit. It seems likely that initiation is activated because of NF-kappaB's ability to disrupt chromatin structures through the recruitment of histone acetyltransferases. To test whether p65 could stimulate elongation under conditions where it did not affect histone acetylation, cells were treated with the histone deacetylase inhibitor trichostatin A. Remarkably, addition of p65 to the trichostatin A-treated cell lines resulted in a dramatic increase in transcription elongation, reaching levels equivalent to those observed in the presence of Tat. We suggest that the activation of elongation by NF-kappaB p65 involves a distinct biochemical mechanism, probably the activation of carboxyl-terminal domain kinases at the promoter.
Rostafuroxin: an ouabain antagonist that corrects renal and vascular Na+-K+- ATPase alterations in ouabain and adducin-dependent hypertension (2006)

The genetic and environmental heterogeneity of essential hypertension is responsible for the individual variability of antihypertensive therapy. An understanding of the molecular mechanisms underlying hypertension and related organ complications is a key aspect for developing new, effective, and safe antihypertensive agents able to cure the cause of the disease. Two mechanisms, among others, are involved in determining the abnormalities of tubular Na+ reabsorption observed in essential hypertension: the polymorphism of the cytoskeletal protein alpha-adducin and the increased circulating levels of endogenous ouabain (EO). Both lead to increased activity and expression of the renal Na+-K+ pump, the driving force for tubular Na transport. Morphological and functional vascular alterations have also been associated with EO. Rostafuroxin (PST 2238) is a new oral antihypertensive agent able to selectively antagonize EO, adducin pressor, and molecular effects. It is endowed with high potency and efficacy in reducing blood pressure and preventing organ hypertrophy in animal models representative of both adducin and EO mechanisms. At molecular level, in the kidney, Rostafuroxin antagonizes EO triggering of the Src-epidermal growth factor receptor (EGFr)-dependent signaling pathway leading to renal Na+-K+ pump, and ERK tyrosine phosphorylation and activation. In the vasculature, it normalizes the increased myogenic tone caused by nanomolar ouabain. A very high safety ratio and an absence of interaction with other mechanisms involved in blood pressure regulation, together with initial evidence of high tolerability and efficacy in hypertensive patients, indicate Rostafuroxin as the first example of a new class of antihypertensive agents designed to antagonize adducin and EO-hypertensive mechanisms.
Controlled gene expression systems for Lactococcus lactis with the food-grade inducer nisin (1996)

The kinetics, control, and efficiency of nisin-induced expression directed by the nisA promoter region were studied in Lactococcus lactis with transcriptional and translational fusions to the gusA reporter genes. In the nisin-producing L. lactis strain NZ9700, the specific beta-glucuronidase activity increased very rapidly after mid-exponential growth until the maximum level at the start of the stationary phase was reached. Expression of the gusA gene was also studied in L. lactis NZ9800, an NZ9700 derivative carrying a deletion in the structural nisA gene that abolishes nisin production, and in L. lactis NZ3900, an MG1363 derivative containing the regulatory nisRK genes integrated in the chromosome. In both strains, beta-glucuronidase activity was linearly dependent on the amount of nisin added to the medium. Without nisin, no beta-glucuronidase production was observed. To optimize translation initiation, an expression vector was constructed by fusing the gusA gene translationally to the start codon of the nisA gene. Use of the translational fusion vector yielded up to six times more beta-glucuronidase activity than the transcriptional fusion vector in these strains after induction by nisin. In this way, gene expression can be achieved in a dynamic range of more than 1,000-fold. The beta-glucuronidase activity was found to be up to 25-fold higher in extracts of strain NZ3900 than in extracts of strain NZ9800. This translational fusion vector was used for high-level production of aminopeptidase N, up to 47% of the total intracellular protein. These results clearly illustrate the potential of the nisin-inducible expression system for overproduction of desired proteins.
The double-helix point spread function enables precise and accurate measurement of 3D single-molecule localization and orientation (2013)

Single-molecule-based super-resolution fluorescence microscopy has recently been developed to surpass the diffraction limit by roughly an order of magnitude. These methods depend on the ability to precisely and accurately measure the position of a single-molecule emitter, typically by fitting its emission pattern to a symmetric estimator (e.g. centroid or 2D Gaussian). However, single-molecule emission patterns are not isotropic, and depend highly on the orientation of the molecule’s transition dipole moment, as well as its z-position. Failure to account for this fact can result in localization errors on the order of tens of nm for in-focus images, and ~50-200 nm for molecules at modest defocus. The latter range becomes especially important for three-dimensional (3D) single-molecule super-resolution techniques, which typically employ depths-of-field of up to ~2 μm. To address this issue we report the simultaneous measurement of precise and accurate 3D single-molecule position and 3D dipole orientation using the Double-Helix Point Spread Function (DH-PSF) microscope. We are thus able to significantly improve dipole-induced position errors, reducing standard deviations in lateral localization from ~2x worse than photon-limited precision (48 nm vs. 25 nm) to within 5 nm of photon-limited precision. Furthermore, by averaging many estimations of orientation we are able to improve from a lateral standard deviation of 116 nm (~4x worse than the precision, 28 nm) to 34 nm (within 6 nm).
Collection and Preservation of Frozen Microorganisms (2010)

The storage of the different microorganisms over long periods is necessary to ensure reproducible results and continuity in research and in biomedical processes and also for commercial purposes. Effective storage means that a microorganism is maintained in a viable state free of contamination or genetic drift and must be easily restored without genotypic or phenotypic alterations to its original characteristics and properties. To this end, different techniques have been described and advances in cryopreservation technology have led to methods that allow low-temperature maintenance of a variety of cell types, minimizing the risks of genetic change and are now recommended for long-term storage of most microorganisms.This chapter summarizes the most important steps and components in the process of low- and -ultra-low temperatures freezing of bacteria, parasites, yeasts and fungi, viruses, and recombinant microorganisms.
The Co-Occurrence of Autism and Attention Deficit Hyperactivity Disorder in Children â€“ What Do We Know? (2014)

Symptoms of attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD) often co-occur. The DSM-IV had specified that an ASD diagnosis is an exclusion criterion for ADHD, thereby limiting research of this common clinical co-occurrence. As neurodevelopmental disorders, both ASD and ADHD share some phenotypic similarities, but are characterized by distinct diagnostic criteria. The present review will examine the frequency and implications of this clinical co-occurrence in children, with an emphasis on the available data regarding pre-school age. The review will highlight possible etiologies explaining it, and suggest future research directions necessary to enhance our understanding of both etiology and therapeutic interventions, in light of the new DSM-V criteria, allowing for a dual diagnosis.
Effects of angiotensin II and angiotensin II antagonist saralasin on cell growth and renin in 3T3 and SV3T3 cells (1979)

Components of the renin-angiotensin system were studied in established cell culture lines of 3T3 and SV3T3 mouse fibroblasts. The renin content in 3T3 cells was significantly higher than in virus-transformed SV3T3 cells. With time after infection, renin decreased in Simian virus 40 transformed cells, while it increased steadily in mock-infected 3T3 cells. In contrast to renin, angiotensinase activity was higher in SV3T3 cells. Angiotensin II stimulated cell proliferation in 3T3 mouse fibroblasts and decreased their renin content in a dose-related manner. In contrast, saralasin, an angiotensin receptor antagonist, inhibited cell growth in 3T3 and SV3T3 cells and caused an increase of cellular renin concentration. The angiotensin fragments angiotensin (2-8) heptapeptide and angiotensin (4-8) pentapeptide had no effect on cell growth. A significant negative correlation was found between cell proliferation and renin levels in 3T3 and SV3T3 cells irrespective of the treatment. Our results indicate (1) that angiotensin II may be involved in cell growth regulation, (2) that a negative feedback exist between angiotensin II added and intracellular renin content, and (3) that virus infection causes a decrease in intracellular renin synthesis, while non-specific angiotensinase activity is increased under this condition.
Optimal overlapped message passing decoding for quasi-cyclic low-density parity-check codes (2005)

In this paper, we first present a general scheduling model for the overlapped message passing (OMP) decoding of LDPC codes, and show that maximizing the throughput amounts to minimizing the intra- and inter-iteration waiting times. Then we focus on maximizing the throughput for OMP decoders of quasi-cyclic (QC) LDPC codes using a partly parallel hardware structure, which can be modelled as a data dependency and hardware constrained optimization problem. Finally, we propose a scheduling scheme, which gives the optimal solution to the optimization problem under certain conditions. In comparison to previously proposed scheduling schemes, our new scheduling scheme leads to both higher hardware utilization efficiency (HUE) and greater throughput gain.
Rapid synthesis of N,N′-disubstituted piperazines. Application to the preparation of No carrier added 1-(4-[18F]fluorophenyl)piperazine and of an [18F]-selective ligand of serotoninergic receptors (5HT2antagonist) (1992)

An efficient and rapid method of piperazine formation (>50%, 30 min) involving the reaction of N,O,O′-tris(toluene-p-sulfonyl)bis(2-hydroxyethyl)amine 3 and 4-fluoroaniline in an alcohol or in hexamethylphosphoramide has been developed. It has been applied to the preparation of 1-(4-[18F]fluorophenyl)piperazine 6b, a new precursor in [18F]-labelling for positron emission tomography studies. Compound 6b was obtained in 7–15% decay corrected radiochemical yield in a synthesis time of 145–165 min counted from the labelled precursor [18F]fluoride and a radiochemical purity greater than 98% after HPLC purification. The utility of 6b was demonstrated by the synthesis of the [18F]naphthosultam 8b, a selective antagonist of 5-HT2 receptors. Compound 8b was obtained radiochemically pure in 50 min from 6b(including HPLC) and in an overall yield of 2.5–12%(decay corrected) from [18F]fluoride.
A Modified Microchamber Method for Chemotaxis and Chemokinesis (1984)

A 48 well chemotaxis microchamber, originally designed for use with polycarbonate filters, was used with nitrocellulose filters to quantitate chemotaxis and chemokinesis of granulocytes. Various features of the microchamber were compared to Boyden chambers. The accuracy and reproducibility of the method were found to be comparable to Boyden chambers in the variability between individual readings and superior in the variability between replicate values. Concentrations of optimal doses of chemoattractant for chemotaxis and chemokinesis were similar using both types of chamber. The data indicates that this method may be useful in studying components of the chemotactic response which require the use of cellulose filters. Advantages of this method over standard Boyden chambers include the use of a single filter rather than individual, non-identical filters and a reduction in the number of cells required, particularly for pediatric testing or in neutropenic patients.
A New RNA Dimension to Genome Control (2006)

The discovery of small RNAs, microRNA and siRNA, has revolutionized thinking about the control of gene expression. Now a third new species of small RNA is shown to control gene expression in germline cells.
Effects of moistening, salinity and competitive interactions on vitality and production activity of Salicorniaeuropaea (Chenopodiaceae) (2005)

Dynamics of competitive interactions in populations of annual euhalophyte S. europaea was investigated. For S. europaea the hypothesis of Newman and Tilman is confirmed, concerning presence of intensive competition between plants on unproductive habitats for soil resources. Vital state of plants in populations of S. europaea is determined by intensity of competitive interactions, level of humidity and degree of salinity of ecotype. On an example of S. europaea, productive activity of plants on salted habitats was analyzed and the role of interspecific competition in this process was determined.
Seeding and Implantation of a Biosynthetic Tissue-engineered Tracheal Graft in a Mouse Model (2019)

Treatment options for congenital or secondary long segment tracheal defects have historically been limited due to an inability to replace functional tissue. Tissue engineering holds great promise as a potential solution with its ability to integrate cells and signaling molecules into a 3-dimensional scaffold. Recent work with tissue engineered tracheal grafts (TETGs) has seen some success but their translation has been limited by graft stenosis, graft collapse, and delayed epithelialization. In order to investigate the mechanisms driving these issues, we have developed a mouse model for tissue engineered tracheal graft implantation. TETGs were constructed using electrospun polymers polyethylene terephthalate (PET) and polyurethane (PU) in a mixture of PET and PU (20:80 percent weight). Scaffolds were then seeded using bone marrow mononuclear cells isolated from 6-8 week-old C57BL/6 mice by gradient centrifugation. Ten million cells per graft were seeded onto the lumen of the scaffold and allowed to incubate overnight before implantation between the third and seventh tracheal rings. These grafts were able to recapitulate the findings of stenosis and delayed epithelialization as demonstrated by histological analysis and lack of Keratin 5 and Keratin 14 basal epithelial cells on immunofluorescence. This model will serve as a tool for investigating cellular and molecular mechanisms involved in host remodeling.
Mobilization of stem cells by granulocyte colony-stimulating factor for the regeneration of myocardial tissue after myocardial infarction (2004)

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study
Structural Versus Functional Modulation of the Arterial Baroreflex (1995)

Structural changes in large arteries are often considered the predominant mechanism responsible for decreased baroreflex sensitivity and baroreceptor resetting in hypertension, atherosclerosis, and aging. Recent work has demonstrated that "functional" mechanisms, both at the level of the peripheral sensory endings and within the central nervous system, contribute significantly to altered baroreflex responses. We have conducted both reductive studies of mechanoelectrical transduction in cultured baroreceptor neurons and integrative studies with in vivo recordings of the activity of baroreceptor afferent fibers and efferent sympathetic nerves. Results suggest that the primary mechanism of mechanical activation of baroreceptor neurons involves opening of stretch-activated ion channels susceptible to blockade by gadolinium. Baroreceptor nerve activity is modulated by the activity of potassium channels and the sodium-potassium pump and by paracrine factors, including prostacyclin, oxygen free radicals, and factors released from aggregating platelets. Endothelial dysfunction and altered release of these paracrine factors contribute significantly to the decreased baroreceptor sensitivity in hypertension and atherosclerosis. The central mediation of the baroreflex depends on the pulse phasic pattern of afferent baroreceptor discharge. Baroreflex-mediated inhibition of sympathetic nerve activity is well maintained during pulse phasic afferent activity. Continuous, nonphasic baroreceptor discharge or a rapid (> 1.5 Hz) pulse phasic discharge results in disinhibition of sympathetic activity. This disinhibition during continuous baroreceptor input is exaggerated with aging. Thus, a defect in central mediation of the baroreflex may be a major cause of the impaired baroreflex and sympathoexcitation in the elderly. In summary, functional neural mechanisms, in addition to structural vascular changes, contribute importantly to altered baroreflex responses in normal and pathophysiological states.(ABSTRACT TRUNCATED AT 250 WORDS)
High Resistivity GaN Single Crystalline Substrates (1997)

High resistivity 104 -106 cm (300 K) GaN single crystals were obtained by solution growth under high 2 pressure from melted Ga with 0.1-0.5at.% of Mg. Properties of these crystals are compared with properties of conductive crystals grown by a similar method from pure Ga melt. In particular, it is shown that Mg-doped GaN crystals have better structural quality in terms of FWHM of X-ray rocking curve and low angle boundaries. Temperature dependence of electrical resistivity suggests hopping mechanism of conductivity. It is also shown that strain free GaN homoepitaxial layers can be grown on the Mg-doped GaN substrates.
Asymmetric Calcium Catalysis: Highly Enantioselective Carbonyl‐Ene and Friedel–Crafts Reactions for the Synthesis of Quaternary α‐Hydroxy Esters Bearing a Trifluoromethyl Group (2012)

Enantioselective calcium-catalyzed addition reactions of styrene and indole derivatives with trifluoropyruvates have been developed. The alkaline-earth metal-catalyzed reactions proceed smoothly to afford the corresponding products in high yields and with good to excellent enantioselectivities under mild reaction conditions.
What makes cells move: requirements and obstacles for spontaneous cell motility (2010)

Movement of individual cells and of cellular cohorts, chains or sheets requires physical forces that are established through interactions of cells with their environment. In vivo, migration occurs extensively during embryonic development and in adults during wound healing and tumorigenesis. In order to identify the molecular events involved in cell movement, in vitro systems have been developed. These have contributed to the definition of a number of molecular pathways put into play in the course of migratory behaviours, such as mesenchymal and amoeboid movement. More recently, our knowledge of migratory modes has been enriched by analyses of cells exploring and moving through three-dimensional (3D) matrices. While the cells' morphologies differ in 2D and 3D environments, the basic mechanisms that put a cellular body into motion are remarkably similar. Thus, in both 2D and 3D, the polarity of the migrating cell is initially defined by a specific subcellular localization of signalling molecules and components of molecular machines required for motion. While the polarization can be initiated either in response to extracellular signalling or be a chance occurrence, it is reinforced and sustained by positive feedback loops of signalling molecules. Second, adhesion to a substratum is necessary to generate forces that will propel the cell engaged in either mesenchymal or ameboid migration. For collective cell movement, intercellular coordination constitutes an additional requirement: a cell cohort remains stationary if individual cells pull in opposite directions. Finally, the availability of space to move into is a general requirement to set cells into motion. Lack of free space is probably the main obstacle for migration of most healthy cells in an adult multicellular organism. Thus, the requirements for cell movement are both intrinsic to the cell, involving coordinated signalling and interactions with molecular machines, and extrinsic, imposed by the physicochemical nature of the environment. In particular, the geometry and stiffness of the support act on a range of signalling pathways that induce specific cell migratory responses. These issues are discussed in the present review in the context of published work and our own data on collective migration of hepatocyte cohorts.