gebhart/patrepeval huggingface dataset:
Abnormal synapse formation in agrin-depleted hippocampal neurons (1999)

Agrin, a 200 kDa extracellular matrix protein, participates in the maturation of the postsynaptic target at the neuromuscular junction. Although agrin has also been detected in central neurons, little is known about its role in the formation of their synapses. In the present study, the pattern of expression, localization and function of agrin in developing hippocampal neurons were analyzed. The results indicate that an increase in agrin protein levels precedes synaptogenesis in cultured hippocampal neurons. This increase in agrin expression is accompanied by its extracellular deposition along the distal third of the axon. To investigate whether agrin plays a role during synapse formation, its expression in cultured hippocampal neurons was suppressed by means of antisense oligonucleotide treatment. The suppression of agrin expression results in the impairment of dendritic development and the formation of fewer synapses than in non-treated or sense-treated neurons. Moreover, this decreased synaptic density is accompanied by a selective inhibition of the clustering of GABA receptors. These results lead to the conclusion that agrin may be an important regulator of the maturation of dendrites and synaptogenesis in central neurons.
Subcellular localization of the b-cytochrome component of the human neutrophil microbicidal oxidase: translocation during activation. (1983)

We describe a new method for subcellular fractionation of human neutrophils. Neutrophils were disrupted by nitrogen cavitation and the nuclei removed by centrifugation. The postnuclear supernatant was applied on top of a discontinuous Percoll density gradient. Centrifugation for 15 min at 48,000 g resulted in complete separation of plasma membranes, azurophil granules, and specific granules. As determined by ultrastructure and the distribution of biochemical markers of these organelles, approximately 90% of the b-cytochrome in unstimulated cells was recovered from the band containing the specific granules and was shown to be in or tightly associated with the membrane. During stimulation of intact neutrophils with phorbol myristate acetate or the ionophore A23187, we observed translocation of 40-75% of the b-cytochrome to the plasma membrane. The extent of this translocation closely paralleled release of the specific granule marker, vitamin B12-binding protein. These data indicate that the b-cytochrome is in the membrane of the specific granules of unstimulated neutrophils and that stimulus-induced fusion of these granules with the plasma membrane results in a translocation of the cytochrome. Our observations provide a basis for the assembly of the microbicidal oxidase of the human neutrophil.
Embryonic stem cells and potency to induce transplantation tolerance (2003)

In the past 40 years, many protocols have been extensively studied for the induction of sustainable transplantation tolerance which might lead to protection of allografts from immunological injury in the clinical setting. Despite the enormous success in rodents, there is still no established protocol available yet for widespread clinical trials. Whilst clonal deletion, clonal anergy and suppression, now coined regulation, have been elucidated as the key immunological elements of tolerance, a better understanding of these mechanisms has so far done little to improve on the survival of organ transplants in humans. Haematopoietic chimaerism, as previously described by Medawar and colleagues [1], remains the most robust tool for tolerance induction. Unfortunately, bone marrow or haematopoietic stem cell transplantation for patients awaiting solid organ transplantation remains a high risk therapy, due to the dangers of graft-versus-host disease. Most recent data, however, indicate the potential of embryonic stem cells (ESC) to offer a possible solution for low risk induction of multilineage mixed chimaerism and tolerance not involving any immunosuppression, due to their unique property of low immunogenicity and high plasticity. Here, what we know about ESC in various species, and the potency and drawbacks of ESC for widespread clinical use, will be discussed.
Inverse agonism at heptahelical receptors: concept, experimental approach and therapeutic potential (2000)

Inverse agonists (negative antagonists) are ligands that stabilize the inactive conformation (R) of receptors according to the two-state receptor model. The active conformation (R*) of heptahelical receptors, i.e. G protein-coupled receptors, has high affinity for G proteins. According to ternary complex models of receptor activation, the R*G complex is in equilibrium with R + G, with spontaneous activity in the absence of agonist. Inverse agonists, having a higher affinity for R, shift R*G towards R + G, decreasing the spontaneous activity of receptors. Agonists have the opposite effect, with a higher affinity for R*. Neutral antagonists have the same affinity for R and R* and compete for both agonists and inverse agonists. Inverse agonists have been recently proposed for a variety of heptahelical receptors. Methods to detect inverse agonists among antagonists are based on the determination of ligand affinity at R and R* with binding experiments, and on the modulation of G protein activity (GTP binding and hydrolysis) or of effector activity. Receptor inverse agonists, but also G protein antagonists and GTPase inhibitors, decrease spontaneous G protein activity corresponding to R*G. Receptor agonists, G protein agonists and GTPase inhibitors increase effector basal activity, but receptor inverse agonists decrease it. The therapeutic potential of inverse agonists is proposed in human diseases ascribed to constitutively active mutant receptors and may be extended to diseases related to wild-type receptor over-expression leading to the increase of R*. Some of the therapeutic effects of presently used receptor antagonists may be related to their inverse agonist properties. Inverse agonists lead to receptor upregulation, offering new approaches to tolerance and dependence to drugs.
Circulating IgG response to stromelysin-3, collagenase-3, galectin-3 and mesothelin in patients with pharynx/larynx squamous cell carcinoma. (2002)

With the aim of identifying tumor-associated antigens that could be potential markers and/or targets of diagnostic and/or therapeutic approaches, we studied the occurrence of circulating IgG antibodies to human stromelysin-3, collagenase-3, galectin-3 and mesothelin, by Western blot against their purified recombinant forms, in the sera of 50 patients with pharynx/larynx squamous cell carcinoma (PLSCC), as well as in the sera of 50 healthy blood donors. Overall, antibodies to collagenase-3 were detected in 50% of all the cancer patients and 16% of the blood donors examined; this percentage difference was statistically significant (p = 0.00066). With respect to anti-galectin-3 antibodies, the percentages were 32% and 18%, respectively, but they were not statistically different (p = 0.16). Low levels of antibodies to stromelysin-3 and to mesothelin were detected in sera from only two cancer patients. No significant correlations were found in the present study between the presence of antibodies to these proteins and tumor site, clinical and T stages, lymph node involvement, DNA ploidy and histological grade of differentiation of the primary tumors. To our knowledge, this is the first report on the detection of circulating IgG to collagenase-3 in cancer patients. Some of the percentages found here in certain groups of patients are among the highest reported of circulating antibodies to any tumor component studied so far. The monitoring and the use of human antibodies to collagenase-3 could be of diagnostic and therapeutic interest.
Intracerebral haemorrhage after thrombolysis for acute ischaemic stroke: an update (2008)

Intracerebral haemorrhage (ICH) still represents the most feared complication of thrombolysis. Our aim was to review the literature regarding clinical, biological and imaging predictors of ICH following thrombolysis for acute ischaemic stroke. Relevant studies were identified through a search in Pubmed, using the following key words: "intracerebral", "haemorrhage", "stroke" and "thrombolytic". The query was limited to studies published in the English literature. The reference lists of all relevant articles were reviewed to identify additional studies. The main predictors of clinically significant ICH were age, clinical stroke severity, as assessed by the National Institute of Health Stroke Scale score on admission, high blood pressure, hyperglycaemia, early CT changes, large baseline diffusion lesion volume and leukoaraiosis on MRI. The contribution of biomarkers in the prediction of the ICH risk is currently under evaluation. Available data on patients with limited number of microbleeds on pretreatment gradient echo MRI sequences suggest safe use of thrombolysis. ICH after stroke thrombolysis is a complex and heterogeneous phenomenon, which involves numerous parameters whose knowledge remains partial. To minimise the risk of tissue plasminogen activator (tPA) related symptomatic ICH, careful attention must be given to the pre-therapeutic glycaemia value, and a strict protocol for the control of elevated blood pressure is needed during the first 24 h. Future research should focus on predictors of severe intracerebral haemorrhagic complications (parenchymal haematomas type 2 according to the European Cooperative Acute Stroke Study (ECASS) classification). The input of multimodal MRI and biological predictors of ICH deserves further investigation.
Eales' disease: accumulation of reactive oxygen intermediates and lipid peroxides and decrease of antioxidants causing inflammation, neovascularization and retinal damage (1997)

Lowered levels of antioxidant vitamins E and C and consequent accumulation of oxygen and lipid free radicals, or vice versa, could explain the inflammation, neovascularization and retinal pathology in patients with Eales' disease. Also, vitamin A deficiency could aggravate retinal illness.
Binding Interactions of Human Interleukin 5 with Its Receptor α Subunit (1995)

Human interleukin 5 (hIL5) and soluble forms of its receptor alpha subunit were expressed in Drosophila cells and purified to homogeneity, allowing a detailed structural and functional analysis. B cell proliferation confirmed that the hIL5 was biologically active. Deglycosylated hIL5 remained active, while similarly deglycosylated receptor alpha subunit lost activity. The crystal structure of the deglycosylated hIL5 was determined to 2.6-A resolution and found to be similar to that of the protein produced in Escherichia coli. Human IL5 was shown by analytical ultracentrifugation to form a 1:1 complex with the soluble domain of the hIL5 receptor alpha subunit (shIL5R alpha). Additionally, the relative abundance of ligand and receptor in the hIL5.shIL5R alpha complex was determined to be 1:1 by both titration calorimetry and SDS-polyacrylamide gel electrophoresis analysis of dissolved cocrystals of the complex. Titration microcalorimetry yielded equilibrium dissociation constants of 3.1 and 2.0 nM, respectively, for the binding of hIL5 to shIL5R alpha and to a chimeric form of the receptor containing shIL5R alpha fused to the immunoglobulin Fc domain (shIL5R alpha-Fc). Analysis of the binding thermodynamics of IL5 and its soluble receptor indicates that conformational changes are coupled to the binding reaction. Kinetic analysis using surface plasmon resonance yielded data consistent with the Kd values from calorimetry and also with the possibility of conformational isomerization in the interaction of hIL5 with the receptor alpha subunit. Using a radioligand binding assay, the affinity of hIL5 with full-length hIL5R alpha in Drosophila membranes was found to be 6 nM, in accord with the affinities measured for the soluble receptor forms. Hence, most of the binding energy of the alpha receptor is supplied by the soluble domain. Taken with other aspects of hIL5 structure and biological activity, the data obtained allow a prediction for how 1:1 stoichiometry and conformational change can lead to the formation of hIL5.receptor alpha beta complex and signal transduction.
Characterization of an almost full-length cDNA coding for human blood coagulation factor X. (1985)

A human liver cDNA library was screened by colony hybridization with a bovine factor X cDNA probe. Three of the positive plasmids contained overlapping DNA that coded for most of human factor X mRNA. DNA sequence analysis of these three clones allowed the prediction of the complete amino acid sequence of plasma factor X. From these studies, we predict that human factor X is synthesized as a single polypeptide chain precursor in which the light and heavy chains of plasma factor X are linked by the tripeptide Arg-Lys-Arg. The cDNA sequence also predicts that human factor X is synthesized as a preproprotein having an amino-terminal leader peptide of at least 28 amino acid residues. A comparison of the amino acid sequences of human and bovine factor X shows high sequence identity around the calcium-binding regions and catalytic regions but low sequence identity around the nonfunctional regions.
Prevalence of Gardnerella vaginalis and Atopobium vaginae in Virginal Women (2006)

This study shows that nonpenetrative intimate sexual contact is associated with carriage of G. vaginalis in virginal women.
Isolation of Single-Copy Human Genes from a Library of Yeast Artificial Chromosome Clones (1989)

A recently developed cloning system based on the propagation of large DNA molecules as linear, artificial chromosomes in the yeast Saccharomyces cerevisiae provides a potential method of cloning the entire human genome in segments of several hundred kilobase pairs. Most application of this system will require the ability to recover specific sequences from libraries of yeast artificial chromosome clones and to propagate these sequences in yeast without alterations. Two single-copy genes have now been cloned from a library of yeast artificial chromosome clones that was prepared from total human DNA. Multiple, independent isolates were obtained of the genes encoding factor IX and plasminogen activator inhibitor type 2. The clones, which ranged in size from 60 to 650 kilobases, were stable on prolonged propagation in yeast and appear to contain faithful replicas of human DNA.
AI and the Ethics of Automating Consent (2018)

AI systems collect, process, and generate data in ways that further exacerbate many long-documented problems with online consent, most notably issues of providing adequate notice, choice, and withdrawal to users. The unpredictable and even unimaginable use of data by AI systems is considered a feature, not a bug. Yet this feature creates problems for notifying users as well as assessing when consent might be required based on potential uses, harms, and consequences. This article investigates whether these problems impact morally transformative consent in AI systems. We argue that while supplementing consent with further mechanization, digitization, and intelligence-either through proffering notification on behalf of the consentee or choosing and communicating consent by the consenter-may improve take-it-or-leave-it notice and choice consent regimes, the goal for AI consent should be one of partnership development between parties, built on responsive design and continual consent.
The Best Bits in an Iris Code (2008)

Iris biometric systems apply filters to iris images to extract information about iris texture. Daugman's approach maps the filter output to a binary iris code. The fractional Hamming distance between two iris codes is computed and decisions about the identity of a person are based on the computed distance. The fractional Hamming distance weights all bits in an iris code equally. However, not all the bits in an iris code are equally useful. Our research is the first to present experiments documenting that some bits are more consistent than others. Different regions of the iris are compared to evaluate their relative consistency, and contrary to some previous research, we find that the middle bands of the iris are more consistent than the inner bands. The inconsistent-bit phenomenon is evident across genders and different filter types. Possible causes of inconsistencies, such as segmentation, alignment issues, and different filters are investigated. The inconsistencies are largely due to the coarse quantization of the phase response. Masking iris code bits corresponding to complex filter responses near the axes of the complex plane improves the separation between the match and nonmatch Hamming distance distributions.
F9 Malmo, factor IX and deep vein thrombosis (2009)

The F9 Malmö sequence variant was the most strongly associated with deep vein thrombosis among common single-nucleotide polymorphisms in the region. However, the biological mechanism by which F9 Malmö affects risk remains unknown.
Inverse Targeting of Retroviral Vectors: Selective Gene Transfer in a Mixed Population of Hematopoietic and Nonhematopoietic Cells (1998)

Abstract We previously reported that retroviral vectors displaying epidermal growth factor (EGF) as part of a chimeric envelope glycoprotein are sequestered upon binding to EGF receptor (EGFR)-positive target cells, leading to loss of infectivity. In the current study, we have displayed stem cell factor (SCF) on β-galactosidase-transducing ecotropic and amphotropic retroviral vector particles as a factor Xa protease-cleavable N-terminal extension of the envelope glycoprotein. Viral incorporation of the SCF chimeric envelopes was demonstrated by immunoblotting of pelleted virions and their specific attachment to Kit receptors was demonstrated by flow cytometry. Gene transfer studies showed that when SCF was displayed on an amphotropic envelope, the infectivity of the SCF-displaying vectors was selectively inhibited on Kit-expressing cells, but could be restored by adding soluble SCF to block the Kit receptors or by cleaving the displayed SCF domain from the vector particles with factor Xa protease. The host range properties of EGF-displaying and SCF-displaying vectors were then compared in cell mixing experiments. When EGFR-positive cancer cells and Kit-positive hematopoietic cells were mixed and exposed to the different engineered vector particles, the cancer cells were selectively transduced by the SCF-displaying vector and the hematopoietic cells were selectively transduced by the EGF-displaying vector. Retroviral display of polypeptide growth factors can therefore provide the basis for a novel inverse targeting strategy with potential use for selective transduction of hematopoietic or nonhematopoietic cells (eg, cancer cells) in a mixed cell population.
Effect of Tire Derived Aggregate on Maximum Dry Density of Kaolin (2013)

The use of Tire-Derived Aggregates (TDA) as highly permeable light weight material has been highlighted in different aspects of geotechnical engineering such as retaining walls, embankments and roads. In addition, in terms of human health and environmental matters, TDA usage is gaining attention. This paper gives an insight into the effect of TDA on the Maximum Dry Density (MDD) of Kaolin. A number of 273 compaction tests, were conducted on both Kaolin and Kaolin-TDA mixtures. Granular (5-8 mm), Granular (1-4 mm), Shredded (6-19 mesh) and Powdery (80 mesh) as various types of TDA, in different percentages from 0% to 60% by weight were mixed with Kaolin. Samples were compacted, using standard proctor procedures in accordance with British Standard. Findings show, that the MDD of Kaolin decreases within the range of 9% to 45%. Apart from that, based on the general results, it is observed that there is a significant change in the MDD of Kaolin-TDA mixture while the changes occurred in Optimum Moisture Content (OMC) is not remarkable. Depending on geotechnical problem, the wide range of the results could be used as a proper source for selecting the optimum percentage of Kaolin-TDA mixture.
CHANGING DRIVER BEHAVIOR WITH ON-BOARD SAFETY MONITORING (2000)

This article focuses on the concept of on-board driver performance devices for truck drivers. It presents some preliminary findings and issues related to a study which is examining on-board safety monitoring technologies and identifying behavioral and management practices which encourage driver acceptance, cooperation, and compliance of these technologies. The safety effectiveness of the devices are also being investigated in the study.
Treating malnutrition with megestrol acetate: literature review and review of our experience. (2002)

Megestrol acetate is a semi-synthetic progestational steroid that was originally used as a therapeutic modality for metastatic breast and endometrial cancers. What was originally considered to be it's most frequent side effect, an increase in appetite and in body weight, has gradually become an established treatment of malnutrition in patients with the acquired immuno-deficiency syndrome or with non-hormone responsive cancers. The use of megestrol acetate in treating malnutrition in older persons, in patients on dialysis and in a number of other situations is currently under investigation. The authors review the evidence available to support the use of megestrol acetate in treating malnutrition in these selected groups, and the problems associated with administering megestrol acetate; they also report on their own experience with megestrol acetate in the geriatric population.
Human Peptidoglycan Recognition Proteins Require Zinc to Kill Both Gram-Positive and Gram-Negative Bacteria and Are Synergistic with Antibacterial Peptides (2007)

Mammals have four peptidoglycan recognition proteins (PGRPs or PGLYRPs), which are secreted innate immunity pattern recognition molecules with effector functions. In this study, we demonstrate that human PGLYRP-1, PGLYRP-3, PGLYRP-4, and PGLYRP-3:4 have Zn(2+)-dependent bactericidal activity against both Gram-positive and Gram-negative bacteria at physiologic Zn(2+) concentrations found in serum, sweat, saliva, and other body fluids. The requirement for Zn(2+) can only be partially replaced by Ca(2+) for killing of Gram-positive bacteria but not for killing of Gram-negative bacteria. The bactericidal activity of PGLYRPs is salt insensitive and requires N-glycosylation of PGLYRPs. The LD(99) of PGLYRPs for Gram-positive and Gram-negative bacteria is 0.3-1.7 muM, and killing of bacteria by PGLYRPs, in contrast to killing by antibacterial peptides, does not involve permeabilization of cytoplasmic membrane. PGLYRPs and antibacterial peptides (phospholipase A(2), alpha- and beta-defensins, and bactericidal permeability-increasing protein), at subbactericidal concentrations, synergistically kill Gram-positive and Gram-negative bacteria. These results demonstrate that PGLYRPs are a novel class of recognition and effector molecules with broad Zn(2+)-dependent bactericidal activity against both Gram-positive and Gram-negative bacteria that are synergistic with antibacterial peptides.
Preptin derived from proinsulin-like growth factor II (proIGF-II) is secreted from pancreatic islet β-cells and enhances insulin secretion (2001)

Pancreatic islet β-cells secrete the hormones insulin, amylin and pancreastatin. To search for further β-cell hormones, we purified peptides from secretory granules isolated from cultured murine βTC6-F7 β-cells. We identified a 34-amino-acid peptide (3948Da), corresponding to Asp69–Leu102 of the proinsulin-like growth factor II E-peptide, which we have termed ‘preptin’. Preptin, is present in islet β-cells and undergoes glucose-mediated co-secretion with insulin. Synthetic preptin increases insulin secretion from glucose-stimulated βTC6-F7 cells in a concentration-dependent and saturable manner. Preptin infusion into the isolated, perfused rat pancreas increases the second phase of glucose-mediated insulin secretion by 30%, while anti-preptin immunoglobulin infusion decreases the first and second phases of insulin secretion by 29 and 26% respectively. These findings suggest that preptin is a physiological amplifier of glucose-mediated insulin secretion.