gebhart/patrepeval huggingface dataset:
Enrichment of fetal nucleated cells from maternal blood: Model test system using cord blood (1995)

The presence of small numbers of fetal nucleated red cells in the maternal circulation has been a stimulus for the development of technologies for non-invasive prenatal genetic analysis. Our laboratory has been assessing the feasibility of density gradient centrifugation followed by magnetic activated cell sorting (MACS) of cells expressing CD32 and CD45, to deplete maternal nucleated blood cells. We have examined the efficiency of each of the steps of this procedure using cord blood from term pregnancies as a source of nucleated red blood cells. Cord blood was shown to contain highly variable numbers of nucleated red cells. Three different density gradients were examined. There was no major difference in the performances of the double and triple gradients. Density gradient centrifugation resulted in enrichments of nucleated red blood cells of about 1000-fold relative to the total cell count. However, it was apparent that the selection of the cell layers which were most enriched for these cells would result in significant losses of nucleated red cells in other layers. MACS sorting of cells using CD45 resulted in white cell depletions ranging from 7 to 34-fold. These data provide a foundation for comparison with other methods and for optimization of the MACS technique.
Folate analogs. 33. Synthesis of folate and antifolate poly-.gamma.-glutamates by [(9-fluorenylmethoxy)oxy]carbonyl chemistry and biological evaluation of certain methotrexate polyglutamate polylysine conjugates as inhibitors of the growth of H35 hepatoma cells (1990)

Representative examples of folate and antifolate poly-gamma-glutamyl metabolites were synthesized via the [(9-fluorenylmethoxy)oxy]carbonyl (Fmoc) chemistry using the KH polyamide resin. Polyglutamate yields were consistently better in all cases compared to the previous Merrifield method, and the crude products were obtained in greater than 85% purity. The symmetrical anhydride (7) derived from alpha-tert-butyl N-Fmoc-L-glutamate (6) was used for the initial coupling of the first glutamate residue to the KH resin and also for subsequent chain elongation. The alpha-tert-butyl protective groups were not labile under the conditions used for the cleavage of the finished peptide from the resin. A series of poly-gamma-glutamyl metabolites of methotrexate (MTX) with a chain length ranging from two to five glutamyl residues were synthesized and coupled with poly(L-lysine) having an average molecular weight of 27,000 and 52,000. Each conjugate was tested for its ability to inhibit the growth of wild type (H35) and MTX transport resistant (H35R) strains of hepatoma cells in culture, the latter having a 100-fold reduced sensitivity to MTX. 4-Amino-4-deoxy-N10-methylpteroylglutamyl-gamma-glutamylpoly (L-lysine) conjugate [MTX(G2)-poly-L-Lys-52000] and MTX(G4)-poly-L-Lys-52000 were among the most active (I50 = 8.0 and 10 nM against H35 cells) MTX-polylysines synthesized to date, and they were somewhat more inhibitory to the transport resistant cells. MTX(G5)-poly-L-Lys-52000 was approximately 1000 times more effective than MTX(G5)-poly-D-Lys-52000 in inhibiting the growth of H35R hepatoma cells in culture, indicating that internal cleavage of the gamma-glutamate chain of the conjugate with subsequent release of MTX or shorter chain polyglutamates of MTX is unlikely to be an important determinant of MTX-polyglutamate polylysine cytotoxicity. The results indicate that MTX-polyglutamate poly(L-lysine) conjugates are taken up by the cells independently of MTX and probably via endocytosis.
MV Long Pulse Generator With Low Ripple And Low Droop (2005)

A compact 1 MV Long Pulse Generator, developed for high power microwave application of electron beam sources, is described. Such applications require voltage pulse flat-top with low ripple (< /spl plusmn/ 1 percent) and low droop (< 2 percent). For the present application variable pulse widths of 0.1 to 10/spl mu/s into a fixed load (200 to 1k/spl Omega/ W) up to 500 kV, and 0.1 to 1/spl mu/s for voltage above 500 kV and up to 1 MV were required. This pulse generator presently in operation in the new Long Pulse Accelerator Facility at the Naval Research Laboratory, Plasma Physics Division.
Improvement of linewidth enhancement factor in 1.55-μm multiple-quantum-well laser diodes (1998)

The improvement of the linewidth enhancement factor in complex-coupled laser diode (CC-LD), or loss-coupled, was confirmed by measuring the spontaneous emission spectra below threshold from the sidewall of laser diodes. In addition, the serial resistance of the device was measured. The linewidth enhancement factor is improved by the presence of a light absorbing InGaAs grating for loss coupled distributed-feedback (DFB) laser diode (LD). We report the comparison of the linewidth enhancement factors of Fabry-Perot (FP) LD, conventional DFB-LD, and loss coupled DFB-LDs.
Neurobehavioral Consequences of Arousals (1996)

The neurobehavioral deficits of obstructive sleep apnea syndrome (OSAS) are often attributed to the rate of respiratory disturbance or rate of arousals during sleep. However, sleep disordered breathing is also associated with other changes in sleep infrastructure that may account for cumulative waking deficits. This was illustrated in polysomnographic data from 1,521 patients with OSAS where increasing arousal indices were associated with increased duration of stage 1 sleep and concomitant reduction in total sleep time. Similar results have been found in paradigms in which sleep was experimentally fragmented in healthy individuals. It appears that chronic fragmentation of sleep, whether by apneas or acoustic stimuli, leads to cumulative homeostatic pressure for sleep, which may explain a number of phenomenon characteristic of both untreated OSAS patients and experimentally fragmented sleepers: (1) increased arousal threshold, (2) rapid return to sleep after arousal, (3) fewer awakenings over time, (4) increased sleep inertia on awakenings, (5) increased amnesia for arousals, and (6) daytime sleepiness. Elevated homeostatic drive for sleep appears to be a function of both the frequency of arousals within a night and the chronicity of sleep fragmentation across nights, neither of which have been adequately modeled in experimental studies of healthy subjects.
A Solid-Phase Labeling Strategy for the Preparation of Technetium and Rhenium Bifunctional Chelate Complexes and Associated Peptide Conjugates (2005)

A new solid-phase labeling strategy for the preparation of (99m)Tc and Re chelate complexes and associated peptide derivatives, was developed. Resin-bound monoamide monoamine (MAMA) chelates were prepared in such a manner that upon the addition of a suitable Re(V) and Tc(V) precursor the target metal complexes were selectively released from the resin. The desired products were isolated from unreacted ligand by a simple filtration/solid-phase extraction procedure. In addition to the preparation of a series of functionalized ligands, a peptide conjugate was constructed from one of the resin-bound chelates using a conventional automated peptide synthesizer. The yields of the Re chelate complexes were typically greater than 70%, while the maximum yield for reactions run at the tracer level using (99m)Tc was 50%. The reported approach has a number of attractive features, including the opportunity to prepare libraries of novel agents, the ability to isolate macroscopic amounts of Re complexes for use in in vitro screening studies and as well-characterized standards for tracer level work, and the ability to produce (99m)Tc complexes that are free of any unreacted starting material without having to employ preparative HPLC.
Estrogen receptors and human disease (2006)

Estrogens influence many physiological processes in mammals, including but not limited to reproduction, cardiovascular health, bone integrity, cognition, and behavior. Given this widespread role for estrogen in human physiology, it is not surprising that estrogen is also implicated in the development or progression of numerous diseases, which include but are not limited to various types of cancer (breast, ovarian, colorectal, prostate, endometrial), osteoporosis, neurodegenerative diseases, cardiovascular disease, insulin resistance, lupus erythematosus, endometriosis, and obesity. In many of these diseases, estrogen mediates its effects through the estrogen receptor (ER), which serves as the basis for many therapeutic interventions. This Review will describe diseases in which estrogen, through the ER, plays a role in the development or severity of disease.
Wavelet importance sampling (2005)

We present a new technique for importance sampling products of complex functions using wavelets. First, we generalize previous work on wavelet products to higher dimensional spaces and show how this product can be sampled on-the-fly without the need of evaluating the full product. This makes it possible to sample products of high-dimensional functions even if the product of the two functions in itself is too memory consuming. Then, we present a novel hierarchical sample warping algorithm that generates high-quality point distributions, which match the wavelet representation exactly. One application of the new sampling technique is rendering of objects with measured BRDFs illuminated by complex distant lighting --- our results demonstrate how the new sampling technique is more than an order of magnitude more efficient than the best previous techniques.
Enhanced sensitivity to IGF-II signaling links loss of imprinting of IGF2 to increased cell proliferation and tumor risk (2007)

Loss of imprinting (LOI) of the insulin-like growth factor-II gene (IGF2), leading to abnormal activation of the normally silent maternal allele, is a common human epigenetic population variant associated with a 5-fold increased frequency of colorectal neoplasia. Here, we show first that LOI leads specifically to increased expression of proliferation-related genes in mouse intestinal crypts. Surprisingly, LOI(+) mice also have enhanced sensitivity to IGF-II signaling, not simply increased IGF-II levels, because in vivo blockade with NVP-AEW541, a specific inhibitor of the IGF-II signaling receptor, showed reduction of proliferation-related gene expression to levels half that seen in LOI(-) mice. Signal transduction assays in microfluidic chips confirmed this enhanced sensitivity with marked augmentation of Akt/PKB signaling in LOI(+) cells at low doses of IGF-II, which was reduced in the presence of the inhibitor to levels below those found in LOI(-) cells, and was associated with increased expression of the IGF1 and insulin receptor genes. We exploited this increased IGF-II sensitivity to develop an in vivo chemopreventive strategy using the azoxymethane (AOM) mutagenesis model. LOI(+) mice treated with AOM showed a 60% increase in premalignant aberrant crypt foci (ACF) formation over LOI(-) mice. In vivo IGF-II blockade with NVP-AEW541 abrogated this effect, reducing ACF to a level 30% lower even than found in exposed LOI(-) mice. Thus, LOI increases cancer risk in a counterintuitive way, by increasing the sensitivity of the IGF-II signaling pathway itself, providing a previously undescribed epigenetic chemoprevention strategy in which cells with LOI are "IGF-II addicted" and undergo reduced tumorigenesis in the colon upon IGF-II pathway blockade.
2-Methoxyestradiol Induces Cell Cycle Arrest and Mitotic Cell Apoptosis in Human Vascular Smooth Muscle Cells (2005)

It has been shown that 2-methoxyestradiol (2-ME) inhibits cell proliferation and DNA synthesis in human aortic smooth muscle cells. However, the cellular mechanisms underlying the antiproliferative activity of 2-ME are unclear. The present study was performed to explore the cellular mechanisms whereby 2-ME leads to growth inhibition and apoptosis of human smooth muscle cells. Our results demonstrate that at 1 hour of treatment, 1 micromol/L 2-ME induces multiple spindles, overamplified centrosomes, and multipolar cytokinesis, whereas 10 micromol/L 2-ME causes completely damaged spindle, disorientated centrosomes, and missegregated chromosomes. At 6 hours of treatment, the mitotic index was increased and reached a maximal level, and cells with 4N DNA content (4N cells) began to accumulate. The increased mitotic cells induced by 2-ME were apoptotic as detected by both annexin V and TUNEL staining. Blockage of cells in G(1/0) phase by thymidine prevented 2-ME-induced apoptosis. In addition, the increased mitotic index declined concurrently when even more 4N cells accumulated at 12 to 48 hours of treatment with 10 micromol/L 2-ME. Furthermore, in response to 2-ME, cells delayed entry into the next cell cycle and exhibited aneuploidy or micronuclei. Some aneuploidy cells continued to synthesize DNA. We conclude that 2-ME treatment not only arrests cells in mitosis and promotes mitotic cell apoptosis, but also causes cells to undergo "mitotic slippage" and endoreduplication. The induction of mitotic cell arrest and apoptosis may be a major cellular mechanism by which 2-ME inhibits proliferation of human smooth muscle cells.
Implication of Raft Microdomains in Drug Induced Apoptosis (2003)

DNA damaging agents such as 1-beta-D-arabinofuranosylcytosine (Ara-C) and daunorubicin (DNR) are widely used in the treatment of acute nonlymphocytic leukemia. These drugs have, of course, been the objects of intense basic research, as well as preclinical and clinical study. Although specific biochemical lesions (DNA damage) have been associated with Ara-C- and DNR-mediated cytotoxicity, the pathways leading to the induction of apoptosis remain ill defined. This standpoint has forced investigators to explore a new concept in cell response to cytotoxic stress: apoptosis signaling. The recent identification of a ceramide (CER) mediated apoptotic signaling pathway triggered by antitumor agents offers a new perspective for the treatment of neoplastic cells. Indeed, these agents have been shown to induce apoptosis through the activation of a sphingomyelinase (SMase) responsible for the hydrolysis of sphingomyelin (SM) and the generation of CER. The latter acts as a potent apoptosis mediator, triggering several downstream signaling pathways among which the stress-activated protein kinase cascade (MEKK1-SEK1-SAP/JNK) plays a critical role in apoptosis induction. However, the spacio-temporal organization of the key early signaling events is unclear. The present review delineates what appears to be a critical factor in apoptosis signaling: sphingomyelin enriched plasma membrane rafts. The apparent topological partitioning between DNA damage and apoptosis signaling (integrated into specialized plasma membrane domains) is discussed.
Automated Crack Detection on Concrete Bridges (2014)

Detection of cracks on bridge decks is a vital task for maintaining the structural health and reliability of concrete bridges. Robotic imaging can be used to obtain bridge surface image sets for automated on-site analysis. We present a novel automated crack detection algorithm, the STRUM (spatially tuned robust multifeature) classifier, and demonstrate results on real bridge data using a state-of-the-art robotic bridge scanning system. By using machine learning classification, we eliminate the need for manually tuning threshold parameters. The algorithm uses robust curve fitting to spatially localize potential crack regions even in the presence of noise. Multiple visual features that are spatially tuned to these regions are computed. Feature computation includes examining the scale-space of the local feature in order to represent the information and the unknown salient scale of the crack. The classification results are obtained with real bridge data from hundreds of crack regions over two bridges. This comprehensive analysis shows a peak STRUM classifier performance of 95% compared with 69% accuracy from a more typical image-based approach. In order to create a composite global view of a large bridge span, an image sequence from the robot is aligned computationally to create a continuous mosaic. A crack density map for the bridge mosaic provides a computational description as well as a global view of the spatial patterns of bridge deck cracking. The bridges surveyed for data collection and testing include Long-Term Bridge Performance program's (LTBP) pilot project bridges at Haymarket, VA, USA, and Sacramento, CA, USA.
Epstein-Barr virus recombinants from overlapping cosmid fragments (1993)

Five overlapping type 1 Epstein-Barr virus (EBV) DNA fragments constituting a complete replication- and transformation-competent genome were cloned into cosmids and transfected together into P3HR-1 cells, along with a plasmid encoding the Z immediate-early activator of EBV replication. P3HR-1 cells harbor a type 2 EBV which is unable to transform primary B lymphocytes because of a deletion of DNA encoding EBNA LP and EBNA 2, but the P3HR-1 EBV can provide replication functions in trans and can recombine with the transfected cosmids. EBV recombinants which have the type 1 EBNA LP and 2 genes from the transfected EcoRI-A cosmid DNA were selectively and clonally recovered by exploiting the unique ability of the recombinants to transform primary B lymphocytes into lymphoblastoid cell lines. PCR and immunoblot analyses for seven distinguishing markers of the type 1 transfected DNAs identified cell lines infected with EBV recombinants which had incorporated EBV DNA fragments beyond the transformation marker-rescuing EcoRI-A fragment. Approximately 10% of the transforming virus recombinants had markers mapping at 7, 46 to 52, 93 to 100, 108 to 110, 122, and 152 kbp from the 172-kbp transfected genome. These recombinants probably result from recombination among the transfected cosmid-cloned EBV DNA fragments. The one recombinant virus examined in detail by Southern blot analysis has all the polymorphisms characteristic of the transfected type 1 cosmid DNA and none characteristic of the type 2 P3HR-1 EBV DNA. This recombinant was wild type in primary B-lymphocyte infection, growth transformation, and lytic replication. Overall, the type 1 EBNA 3A gene was incorporated into 26% of the transformation marker-rescued recombinants, a frequency which was considerably higher than that observed in previous experiments with two-cosmid EBV DNA cotransfections into P3HR-1 cells (B. Tomkinson and E. Kieff, J. Virol. 66:780-789, 1992). Of the recombinants which had incorporated the marker-rescuing cosmid DNA fragment and the fragment encoding the type 1 EBNA 3A gene, most had incorporated markers from at least two other transfected cosmid DNA fragments, indicating a propensity for multiple homologous recombinations. The frequency of incorporation of the nonselected transfected type 1 EBNA 3C gene, which is near the end of two of the transfected cosmids, was 26% overall, versus 3% in previous experiments using transfections with two EBV DNA cosmids. In contrast, the frequency of incorporation of a 12-kb EBV DNA deletion which was near the end of two of the transfected cosmids was only 13%.(ABSTRACT TRUNCATED AT 400 WORDS)
The effects of tamsulosin, a high affinity antagonist at functional α1A‐ and α1D‐adrenoceptor subtypes (1997)

1. The actions of the alpha 1-adrenoceptor antagonist tamsulosin have been examined at functional alpha 1-adrenoceptor subtypes and compared with those at the human prostate receptor. 2. At the alpha 1D-adrenoceptors of the rat aorta, tamsulosin acted as a competitive antagonist with a high affinity (pKB = 10.1). 3. At the alpha 1B-adrenoceptor of the rat spleen and rabbit corpus cavernosum penis, tamsulosin again acted as a competitive antagonist but with a significantly lower affinity (pKB = 8.9-9.2). 4. Tamsulosin acted as an unsurmountable antagonist of the alpha 1A-adrenoceptor-mediated responses of the rat and human vas deferens, reducing maximal responses to phenylephrine by 20% and 50%, respectively, at an antagonist concentration of 1 nM. Responses of depolarized (100 mM KCl) rat vas deferens preparations were unaffected by 10 nM tamsulosin but this concentration reduced maximal responses to 5-hydroxytryptamine (5-HT) in this tissue. 5. When longer antagonist incubation periods (> or = 60 min) were used, tamsulosin behaved as a competitive antagonist on the human prostate with a significantly higher affinity (pKB = 10.0) than obtained at the alpha 1B-adrenoceptor. 6. The data demonstrate that tamsulosin is a high affinity antagonist at functional alpha 1-adrenoceptors with a selectivity alpha 1D > or = alpha 1A > alpha 1B. In some tissues the compound exhibits an additional unsurmountable antagonist action, the clinical significance of which is unknown.
Early pregnancy peripheral blood gene expression and risk of preterm delivery: a nested case control study (2009)

PTD is associated with maternal early pregnancy peripheral blood gene expression changes. Maternal early pregnancy peripheral blood gene expression patterns may be useful for better understanding of PTD pathophysiology and PTD risk prediction.
Concomitant Photosynthesis Implicated in the Light Effect on Translocation in Bean Plants (1969)

Light supplied during a 3-hr translocation period stimulated [14C]sucrose translocation in bean plants, both when the plants had spent the previous 30 hr in the light and when they had spent this period in the dark. Light during the trans-location period was also very effective when the latter was shortened to 30 min and followed a 30-hr pretreatment period in the light. It is thus unlikely that the light effect is due to a change in overall leaf sugar level, since the latter will not have altered markedly during the final 30 min of a light period of more than 30 hr. Not only was more 14C translocated out of the leaves in the light, but a far higher percentage of the 14C so translocated reached the roots.
Role of IL-6 in Asthma and Other Inflammatory Pulmonary Diseases (2012)

The incidence and severity of chronic lung diseases is growing and affects between 100 and 150 million people worldwide and is associated with a significant rate of mortality. Unfortunately, the initial cause that triggers most chronic lung diseases remains unknown and current available therapies only ameliorate, but do not cure the disease. Thus, there is a need for identification of new targets and development of novel therapies especially for those most severely affected. IL-6, like other inflammatory cytokines, has been shown to be elevated in different lung diseases, but it was considered a byproduct of ongoing inflammation in the lung. However, recent studies support a dissociation of IL-6 from inflammation in the lung and suggest that this cytokine plays an active role in pathogenesis of asthma and, in all likelihood, COPD. IL-6 may therefore be a germane target for treatment of these and other chronic lung disease. Here, we provide an overview of the studies in mouse models and human patients that provide support for the involvement of IL-6 in lung diseases.