gebhart/patrepeval huggingface dataset:
Serum Angiopoietin-1 and -2 Levels Discriminate Cerebral Malaria from Uncomplicated Malaria and Predict Clinical Outcome in African Children (2009)

ANG-1 and the ANG-2/1 ratio are promising clinically informative biomarkers for CM. Additional studies should address their utility as prognostic biomarkers and potential therapeutic targets in severe malaria.
Numerical Grid Generation: Foundations and Applications (1985)

Numerical grid generation: foundations and applications , Numerical grid generation: foundations and applications , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
Mechanism of Anti‐DNA Antibody Formation (1986)

The mechanism(s) of anti-DNA antibody formation was comparatively investigated using in vitro human and murine B-cell culture systems. T-cell homogenate (TH) from SLE patients converted normal human B-cells to anti-DNA specific antibody-forming plasma cells (anti-DNA-SPC) when cultured with calf thymic native DNA as antigen. TH of normal human donors suppressed the formation of anti-DNA-SPC from normal human B-cell cultures even when SLE TH and DNA were added to the cultures. B-cells derived from SLE patients were insensitive to normal human TH, and resulted in the formation of many anti-DNA-SPC. TH of young and old NZB mice stimulated the formation of anti-DNA-SPC from not only NZB but also C57BL/6 murine bone marrow cultures in the presence of DNA antigen. Human and murine TH, and both B-cell cultures were reciprocally combined to test whether xenogeneic TH stimulated B-cell cultures from different species. Xenogeneic TH was effective in triggering differentiation of xenogeneic B-cells with respect to anti-DNA-SPC. The elimination of helper T-subsets (Th) resulted in the generation of fewer anti-DNA-SPC, whereas the elimination of suppressor T-subsets (Ts) caused the formation of many anti-DNA-SPC. Among organ homogenates, e.g., liver, kidney and, brain, and T-cells from old NZB mice, TH was most effective in the stimulation of anti-DNA-SPC. The effective substance was sensitive to RNase-A, but resistant to pronase and DNase-I. Phenol extracted T-cell RNA retained its activity. We concluded that the functional modulation of helper T-cells, which reflects RNA molecules, could be the main etiology of autoantibody formation against DNA by both human and murine B-cells.
A monoclonal antibody recognizes an O-acylated sialic acid in a human melanoma-associated ganglioside. (1984)

Monoclonal antibody D1.1 originally prepared against the B49 cell line derived from a rat brain tumor was shown to react with a ganglioside present in fetal rat brain. We have found that this antigen is also present in human malignant melanoma tumors as well as many melanoma cell lines. The ganglioside from human melanoma cell lines migrates between GM1 and GM2 on one-dimensional thin layer chromatography. Analysis by two-dimensional thin layer chromatography with intermediate ammonia treatment suggests that the ganglioside contains one or more base-labile O-acyl esters. Mild base hydrolysis under conditions known to remove O-acyl esters results in complete loss of antigenic reactivity. Thus, the alkali-labile moiety is a critical component of the epitope recognized by the antibody. Analysis of the sialic acids of total gangliosides from [6-3H]glucosamine-labeled melanoma cells showed that approximately 10% of these molecules are O-acylated. Similar analysis of the purified ganglioside showed that greater than 30% of the sialic acids comigrated with authentic 9-O-acetyl-N-acetylneuraminic acid. The antibody did not cross-react with normal human skin melanocytes nor with any of a large number of normal human adult and fetal tissues. The antibody also did not react with numerous other malignant cell lines studied. These findings suggest that the antigenic epitope defined by antibody D1.1 contains an O-acylated sialic acid and may arise from aberrant O-acetylation occurring in human malignant melanoma cells.
Characterization of a Gene for Spinach CAP160 and Expression of Two Spinach Cold-Acclimation Proteins in Tobacco1 (1998)

The cDNA sequence for CAP160, an acidic protein previously linked with cold acclimation in spinach (Spinacia oleracea L.), was characterized and found to encode a novel acidic protein of 780 amino acids having very limited homology to a pair of Arabidopsis thaliana stress-regulated proteins, rd29A and rd29B. The lack of similarity in the structural organization of the spinach and Arabidopsis genes highlights the absence of a high degree of conservation of this cold-stress gene across taxonomic boundaries. The protein has several unique motifs that may relate to its function during cold stress. Expression of the CAP160 mRNA was increased by low-temperature exposure and water stress in a manner consistent with a probable function during stresses that involve dehydration. The coding sequences for CAP160 and CAP85, another spinach cold-stress protein, were introduced into tobacco (Nicotiana tabacum) under the control of the 35S promoter using Agrobacterium tumefaciens-based transformation. Tobacco plants expressing the proteins individually or coexpressing both proteins were evaluated for relative freezing-stress tolerance. The killing temperature for 50% of the cells of the transgenic plants was not different from that of the wild-type plants. As determined by a more sensitive time/temperature kinetic study, plants expressing the spinach proteins had slightly lower levels of electrolyte leakage than wild-type plants, indicative of a small reduction of freezing-stress injury. Clearly, the heterologous expression of two cold-stress proteins had no profound influence on stress tolerance, a result that is consistent with the quantitative nature of cold-stress-tolerance traits.
Novel antigenic markers of human tumor regression. (1988)

The development of tumor-specific antibodies was studied in a group of cancer patients undergoing active specific immunotherapy with irradiated human allogeneic and autochthonous (autologous) tumor cells injected by the intralymphatic route. Immunoblotting studies on extracts of various established tumor cell cultures and fresh tumor biopsies were performed using sera from these patients. Evaluable tumor regressions were associated with detection of antibodies against human tumor cell antigens of 22,000 daltons (22 kd), 38,000 daltons (38 kd), 43,000 daltons (43 kd), and 70,000 daltons (70 kd). Similar antigens of approximately 22, 43, and 70 kd have also been detected in fresh extracts of certain human tumor tissues when tested with antisera from patients responding to immunotherapy. Production of antibodies to these antigens may play a role in tumor regression with active specific immunotherapy. These human regression-associated antigens may, therefore, represent novel agents for cancer immunotherapy.
Deletion of the BH3-only protein puma protects motoneurons from ER stress-induced apoptosis and delays motoneuron loss in ALS mice (2007)

BH3-only proteins couple diverse stress signals to the evolutionarily conserved mitochondrial apoptosis pathway. Previously, we reported that the activation of the BH3-only protein p53-up-regulated mediator of apoptosis (Puma) was necessary and sufficient for endoplasmic reticulum (ER) stress- and proteasome inhibition-induced apoptosis in neuroblastoma and other cancer cells. Defects in protein quality control have also been suggested to be a key event in ALS, a fatal neurodegenerative condition characterized by motoneuron degeneration. Using the SOD1(G93A) mouse model as well as human post mortem samples from ALS patients, we show evidence for increased ER stress and defects in protein degradation in motoneurons during disease progression. Before symptom onset, we detected a significant up-regulation of Puma in motoneurons of SOD1(G93A) mice. Genetic deletion of puma significantly improved motoneuron survival and delayed disease onset and motor dysfunction in SOD1(G93A) mice. However, it had no significant effect on lifespan, suggesting that other ER stress-related cell-death proteins or other factors, such as excitotoxicity, necrosis, or inflammatory injury, may contribute at later disease stages. Indeed, further experiments using cultured motoneurons revealed that genetic deletion of puma protected motoneurons against ER stress-induced apoptosis but showed no effect against excitotoxic injury. These findings demonstrate that a single BH3-only protein, the ER stress-associated protein Puma, plays an important role during the early stages of chronic neurodegeneration in vivo.
Transcript leader regions of two Saccharomyces cerevisiae mRNAs contain internal ribosome entry sites that function in living cells (2001)

In higher eukaryotes, translation of some mRNAs occurs by internal initiation. It is not known, however, whether this mechanism is used to initiate the translation of any yeast mRNAs. In this report, we identify naturally occurring nucleotide sequences that function as internal ribosome entry sites (IRESes) within the 5' leader sequences of Saccharomyces cerevisiae YAP1 and p150 mRNAs. When tested in the 5' untranslated regions of monocistronic reporter genes, both leader sequences enhanced translation efficiency in vegetatively growing yeast cells. Moreover, when tested in the intercistronic region of dicistronic mRNAs, both sequences were shown to contain IRESes that functioned in living cells. The activity of the p150 leader was much greater than that of the YAP1 leader. The second cistron was not expressed in control dicistronic constructs that lacked these sequences or contained the 5' leader sequence of the CLN3 mRNA in the intercistronic region. Further analyses of the p150 IRES revealed that it contained several nonoverlapping segments that were able independently to mediate internal initiation. These results suggested a modular composition for the p150 IRES that resembled the composition of IRESes contained within some cellular mRNAs of higher eukaryotes. Both YAP1 and p150 leaders contain several complementary sequence matches to yeast 18S rRNA. The findings are discussed in terms of our understanding of internal initiation in higher eukaryotes.
A mutant D-amino acid aminotransferase with broad substrate specificity: construction by replacement of the interdomain loop Pro119- Arg120-Pro121 by Gly-Gly-Gly (1998)

D-amino acid aminotransferase (EC 2.6.1.21) catalyzes the interconversion of various D-amino acids and 2-oxo acids. Each homodimer subunit consists of two domains, which are connected by a single loop, Asn118-Pro119-Arg120-Pro121. The loop has no direct contact with the active site region or the cofactor, pyridoxal 5'-phosphate. We attempted to increase the conformational flexibility of this loop through a triple glycine substitution. The resultant mutant P119G-R120G-P121G has features clearly different from the wild-type enzyme under overall as well as half-reaction conditions. The pre-steady-state kinetic analyses of half reactions showed that the mutant enzyme has kmax values higher than the wild-type enzyme towards most D-amino acids examined. A concomitant decrease in substrate affinity (1/Kd), particularly for acidic amino acids, was also observed. A putative binding site for the distal carboxyl group of acidic amino acids in the wild-type enzyme was incidentally displaced by the loop mutation, indicating a functional linkage between the interdomain loop and the active site region. This study has exemplified the usefulness of engineering relatively distant loops as a means to modify substrate specificity of an enzyme.
The role of calcium‐binding proteins in selective motoneuron vulnerability in amyotrophic lateral sclerosis (1994)

The factors contributing to selective motoneuron loss in amyotrophic lateral sclerosis (ALS) remain undefined. To investigate whether calcium-binding proteins contribute to selective motoneuron vulnerability in ALS, we compared calbindin-D28K and parvalbumin immunoreactivity in motoneuron populations in human ALS, and in a ventral spinal cord hybrid cell line selectively vulnerable to the cytotoxic effects of ALS IgG. In human autopsy specimens, immunoreactive calbindin-D28k and parvalbumin were absent in motoneuron populations lost early in ALS (i.e., cortical and spinal motoneurons, lower cranial nerve motoneurons), while motoneurons damaged late or infrequently in the disease (i.e., Onuf's nucleus motoneurons, oculomotor, trochlear, and abducens nerve neurons) expressed markedly higher levels of immunoreactive calbindin-D28K and/or parvalbumin. Motoneuron-neuroblastoma VSC 4.1 hybrid cells lost immunoreactive calbindin-D28k and parvalbumin following dibutyryl-cyclic AMP-induced differentiation and were killed by IgG from ALS patients. Undifferentiated calbindin/parvalbumin-reactive VSC 4.1 cells were not killed, nor were other cell lines expressing high levels of calbindin-D28K and parvalbumin immunoreactivity (substantia nigra-neuroblastoma hybrid cells and N18TG2 neuroblastoma parent cells). These studies suggest that decreased calbindin-D28K and parvalbumin immunoreactivity may help explain the selective vulnerability of motoneurons in ALS.
Microassay for nuclear binding of steroid receptors with use of intact cells from small samples of avian and human tissue. (1988)

A micro version of a nuclear binding assay to assess the biological activity of receptors for steroid hormones was developed for application to small (needle) biopsies of human tumors for the purpose of predicting responses to steroid therapy. This easier assay requires 10-fold less tissue than the original nuclear binding assay described for progesterone receptors in the avian oviduct, endometrium, and endometrial carcinomas (Spelsberg TC, et al., Endocrinology 1987;121:631). We describe the application of this micro assay to normal avian oviduct and cancers of the human breast, and we demonstrate a tissue specificity and saturation of nuclear binding. The micro assay reliably measured as little as 0.5 mg equivalents of tissue per assay tube. Results for breast tumors determined to be estrogen-receptor-positive by the standard dextran-coated charcoal method were also determined with this nuclear binding assay. As described previously for progesterone receptors in endometrial carcinomas, some receptor-positive breast biopsies displayed negligible capacity for nuclear binding. Therefore, with the present assay we have identified nonfunctional receptors in these biopsies, which may be useful for accurate prediction of patients' responses to therapy with hormones.
Cloning, baculovirus expression, and characterization of the alpha subunit of prolyl 4-hydroxylase from the nematode Caenorhabditis elegans. This alpha subunit forms an active alpha beta dimer with the human protein disulfide isomerase/beta subunit. (1994)

Prolyl 4-hydroxylase (EC 1.14.11.2) catalyzes the formation of 4-hydroxyproline in collagens. The vertebrate enzyme is an alpha 2 beta 2 tetramer, the beta subunit of which is identical to protein disulfide-isomerase (PDI). We report here on the cloning of the catalytically important alpha subunit from Caenorhabditis elegans. This polypeptide consists of 542 amino acids and signal peptide of 16 additional residues. The C. elegans alpha subunit is 25 amino acids longer than the human alpha subunit, mainly because of a 32-amino-acid C-terminal extension present only in the former. The overall amino acid sequence identity between these two alpha subunits is 45%, a 127-amino acid region close to the C terminus being especially well conserved. When the C. elegans alpha subunit was expressed together with the human PDI/beta subunit in insect cells by baculovirus vectors, an active prolyl 4-hydroxylase was formed, but surprisingly this C. elegans/human enzyme appeared to be an alpha beta dimer. The specific activity of this C. elegans/human enzyme was comparable with that of the human enzyme, and most of the other catalytic properties were also highly similar. Nevertheless, the C. elegans/human enzyme was not inhibited by poly(L-proline). The data indicate that the multifunctional PDI/beta subunit can form an active prolyl 4-hydroxylase with alpha subunits having marked differences in their amino acid sequences.
The regulatory role of nitric oxide in proinflammatory cytokine expression during the induction and resolution of inflammation (2010)

Upon inflammation, neutrophils and subsequently monocytes infiltrate into the involved site. Neutrophils perform functions such as bacterial killing or tissue destruction and then undergo apoptosis, whereas monocytes differentiate into macrophages at the site. Macrophages and other phagocytes finally clear apoptotic neutrophils, leading to resolution of the inflammation. One of the key steps during inflammation is leukocyte infiltration, which is controlled chiefly by chemokines for neutrophils and monocytes. The production of these chemokines is regulated positively or negatively by iNOS-derived NO. Although the mechanisms underlying such dual effects of NO remain unknown, the level of NO and duration of NO exposure appear to be determining factors. The clearance of apoptotic neutrophils without causing further proinflammatory responses, on the other hand, is another key event during inflammation. The production of proinflammatory cytokines appears to be actively suppressed by TGF-β and NO, which are produced by phagocytes upon interaction with apoptotic cells. Overall, NO plays a critical role during inflammation and therefore, remains a potential target for developing therapeutics for inflammatory diseases.
Why Drugs Fail - A Study on Side Effects in New Chemical Entities (2005)

Over 90% of the market withdrawals were caused by drug toxicity. Hepatotoxicity and cardiovascular toxicity proved to be the major causes for two out of three market withdrawals in the respective time period. In clinical phases I-III 43% of drug development project terminations were due to insufficient efficacy of the investigated compound. The second important issue, which caused one third of the projects to be closed, was toxicity. ADME parameters and economic and other reasons played a minor role. The results of our study indicate that compared with previous studies on this subject, no major improvements have been achieved in the last decade.
Wideband Rapid Interferer Detector Exploiting Compressed Sampling With a Quadrature Analog-to-Information Converter (2015)

We introduce a rapid interferer detector that uses compressed sampling (CS) with a quadrature analog-to-information converter (QAIC). By exploiting bandpass CS, a blind sub-Nyquist sampling approach, the QAIC offers an energy efficient and rapid interferer detection over a wide instantaneous bandwidth. The QAIC front end is implemented in 65 nm CMOS in 0.43 mm 2 and consumes 81 mW from a 1.1 V supply. It senses a frequency span of 1 GHz ranging from 2.7 to 3.7 GHz (PCAST Band) with a resolution bandwidth of 20 MHz in 4.4 μs, 50 times faster than traditional sweeping spectrum scanners. Rapid interferer detector with the bandpass QAIC is two orders of magnitude more energy efficient than traditional Nyquist-rate architectures and one order of magnitude more energy efficient than existing low-pass CS methods. Thanks to CS, the aggregate sampling rate of the QAIC interferer detector is compressed by 6.3 × compared to traditional Nyquist-rate architectures for the same instantaneous bandwidth.
Single-Dose Mucosal Immunization with a Candidate Universal Influenza Vaccine Provides Rapid Protection from Virulent H5N1, H3N2 and H1N1 Viruses (2010)

Mucosal administration of NP and M2-expressing rAd vectors provided rapid and lasting protection from influenza viruses in a subtype-independent manner. Such vaccines could be used in the interval between emergence of a new virus strain and availability of strain-matched vaccines against it. This strikingly effective single-dose vaccination thus represents a candidate off-the-shelf vaccine for emergency use during an influenza pandemic.
Remote, Wireless, Ambulatory Monitoring of Implantable Pacemakers, Cardioverter Defibrillators, and Cardiac Resynchronization Therapy Systems: Analysis of a Worldwide Database (2007)

This broad clinical application of a new monitoring system strongly supports its capability to improve the care of cardiac device recipients, enhance their safety, and optimize the allocation of health resources.
New findings for phenotype–genotype correlations in a large European series of holoprosencephaly cases (2011)

An algorithm is proposed based on these new phenotype-genotype correlations, to facilitate molecular analysis and genetic counselling for HPE.
A Vascular Endothelial Growth Factor Antagonist Is Produced by the Human Placenta and Released into the Maternal Circulation1 (1998)

Vascular endothelial growth factor (VEGF) is a potent secreted factor that promotes angiogenesis and maintains the integrity of the endothelium. Levels of VEGF are increased in many tumors and are elevated in women with pre-eclampsia, a serious disease of pregnancy. Here we show by in situ hybridization that the trophoblast contains the mRNA encoding a soluble version of the VEGF receptor known as Flt-1 (sFlt-1: initially described by Kendall and Thomas, PNAS 90:10705-10709). Binding assays and Western blotting of villus-conditioned media confirmed the production of sFlt-1. Serum from pregnant women was found to contain a VEGF-binding protein that was not present in serum from men or nonpregnant women. As determined by heparin affinity, column fractionation, and cross-linking, this protein was identical to sFlt-1. Taken together, these results show that the placenta secretes sFlt-1, which would be expected to be a VEGF antagonist. This is the first report of production of the sFlt-1 receptor in vivo, and it reveals a new mechanism for naturally regulating this potent angiogenic agent. The presence of such an antagonist suggests that regulation of VEGF action is essential to successful pregnancy. This has important implications for the activity of VEGF locally and systemically in other conditions.
The Diversity of Harmful Algal Bloom-Triggering Mechanisms and the Complexity of Bloom Initiation (2001)

Mechanisms influencing initiation of harmful algal blooms (HABs) are diverse, and are not likely to be mutually exclusive. Rather, initiation of HABs is a result of interactions between processes, which result in biological, physical, and chemical conditions optimal for a bloom. Due to the complexity of some bloom initiation processes, bloom-preventative management may be possible. Results from a modeling exercise and a laboratory experiment indicated that a phytoplankton bloom could be circumvented through manipulation of the nutrient-loading mode, i.e., pulsed vs. continuous loading. These findings, should they prove consistent in more robust field experiments, may provide insights for the development of new management approaches for some HABs. Optimal bloom conditions, however, vary between HAB species. Consequently, it is unlikely that a single management solution will exist. Preventative management efforts will require early warning of HAB initiation, perhaps even before the appearance of an HAB species. An indicator based on the dynamic nature of phytoplankton succession events and phytoplankton species diversity may prove useful for this purpose. Applying this index to an existing plankton data set showed that Microcystis blooms might have been predicted months before the start of the bloom.