gebhart/patrepeval huggingface dataset:
Expression of aberrant O-glycans attached to leukosialin in differentiation-deficient HL-60 cells. (1991)

Promyelocytic leukemia HL-60 cells can be induced to differentiate into granulocytic cells by various agents including retinoic acid (RA), dimethyl sulfoxide, and 6-thioguanine (6-TG). Although the induced cells are no longer capable of proliferation, a few cells continue to divide in the presence of inducers, and these cells are resistant to terminal differentiation by these inducers (R. E. Gallagher, D. A. Giangiulio, C-S. Chang, C. J. Glover, and R. L. Felsted, Blood, 68: 1402-1406, 1986). The present study examined the structures of O-glycans attached to leukosialin, a major sialoglycoprotein in HL-60 cells, and the activities of glycosyltransferases involved in O-glycan synthesis. Leukosialin from RA-resistant and 6-TG-resistant HL-60 sublines migrated much more slowly than those from wild-type HL-60 cells when applied to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The dimethyl sulfoxide-resistant HL-60 subline, on the other hand, expressed leukosialin with a molecular weight similar to wild-type HL-60 cells. RA-resistant and 6-TG-resistant HL-60 cells were found to express a significant amount of tetrasaccharides that contain no sialic acid residue, while wild-type HL-60 cells expressed mainly disialosyl hexasaccharides and contained no detectable amount of asialo-oligosaccharides. Furthermore, wild-type HL-60 cells treated with the inducers for 4 days were found to express the same saccharides present in untreated wild-type HL-60 cells, indicating that the altered O-glycans present in RA and 6-TG sublines were not caused by a direct effect of these agents but rather are intrinsically unique to these sublines. To better understand the mechanisms underlying the differences in O-glycans, the activities of four sialyltransferases were measured: Gal beta 1----3GalNAc alpha 2----3sialyltransferase, Gal beta 1----4(3) GlcNAc alpha 2----3sialyltransferase, Gal beta 1----4GlcNAc alpha 2----6sialyltransferase, and GalNAc alpha 2----6sialyltransferase. Among them, Gal beta 1----3GalNAc alpha 2----3sialyltransferase and Gal beta 1----4(3)GlcNAc alpha 2----3sialyltransferase were much lower in the RA- or 6-TG-resistant HL-60 subline than in wild-type HL-60 cells. These findings indicate that the differences in O-glycans are due to the differences in alpha 2----3sialyltransferase activities. These results strongly suggest that O-glycans associated with leukosialin may play some role in HL-60 cell differentiation.
Interactive Video Object Annotation (2007)

We present interactive techniques for visually annotating independently moving objects in a video stream. Features in the video are automatically tracked and grouped in an off-line preprocess that enables later interactive manipulation and annotation. Examples of such annotations include speech and thought balloons, video graffiti, hyperlinks, and path arrows. Our system also employs a directmanipulation interface for random frame access using spatial constraints. This annotation interface can be employed in a variety of applications including surveillance, film and video editing, visual tagging, and authoring rich media such as hyperlinked video.
Clinical and Pathological Analysis of Deep Mycoses (1991)

Clinical and pathological analysis were performed on 127 cases of deep mycoses diagnosed by autopsy during the 24 years between 1964 and 1987 in Juntendo University Hospital. The following findings were obtained. 1) There has been a tendency for the number of mycoses to increase each year, especially notable for candidiasis and aspergillosis. 2) Underlying diseases were, in order of incidence, various hematologic diseases, solid tumors, inflammatory diseases and collagen diseases; the most common were various types of leukemia. 3) Candidiasis was often observed in patients with gastrointestinal tract cancers. Aspergillosis was often observed in patients with collagen diseases. 4) Regarding the visceral distribution of mycoses, aspergillosis was observed in the lung, candidiasis was observed in the lung, kidney and intestinal tract in decreasing order, and cryptococcosis was also observed in the lung and central nervous system. 5) There was a probability of fungal infections occurring in cases of lymphopenia. 6) A fever was present at the time of hospitalization in many cases of aspergillosis, and the presence of an indwelling catheter was a common feature in cases of candidiasis. 7) Fungemia was frequently observed in candidiasis, but very rarely in cases of aspergillosis. 8) The large amounts of corticosteroid hormones and blood transfusions were suspected as causative factors of fungal infections.
An automated quantitative assay for fungal growth inhibition (1990)

A simple technique which enables the monitoring of fungal growth with the aid of a microplate reader is described. In the absorbance range of 0 to 0.6 units, a straight-line relationship exists between absorbance at 595 nm and dry weight of microplate cultures, indicating that culture absorbance is an accurate indicator of fungal biomass. The relative standard deviation of the absorbance measurements was low (typically between 2 and 6%) when spores were used for inoculum. With inoculi consisting of mycelial fragments, slightly higher standard deviations (ca. 10%) were found. The microplate reader technique is particularly suited for determination of growth inhibition curves, since it is extremely fast, reliable, and requires as little as 75 μl of total culture volume.
Functional domains within the degenerin/epithelial sodium channel (Deg/ENaC) superfamily of ion channels (1999)

Application of recombinant DNA technology and electrophysiology to the study of amiloride-sensitive Na+ channels has resulted in an enormous increase in the understanding of the structure-function relationships of these channels. Moreover, this knowledge has permitted the elucidation of the physiological roles of these ion channels in cellular processes as diverse as transepithelial salt and water movement, taste perception, volume regulation, nociception, neuronal function, mechanosensation, and even defaecation. Although members of this ever-growing superfamily of ion channels (the Deg/ENaC superfamily) share little amino acid identity, they are all organized similarly, namely, two short N- and C-termini, two short membrane-spanning segments, and a very large extracellular loop domain. In this brief Topical Review, we discuss the structural features of each domain of this Deg/ENaC superfamily and, using ENaC as a model, show how each domain relates to overall channel function.
A rapid and noninvasive method to detect dried saliva stains from human skin using fluorescent spectroscopy (2011)

The presence of emission spectrum at 345-355 nm with excitation at 282 nm proves to be a strong indicator of saliva deposited on human skin.
Stability and Selectivity of Unnatural DNA with Five-Membered-Ring Nucleobase Analogues (2002)

In an effort to develop an orthogonal third base pair for the storage of genetic information, thiophene and furan heterocycles have been examined as nucleobase analogues. The stability of the unnatural bases was evaluated in duplex DNA paired opposite other unnatural bases as well as opposite the natural bases. Several unnatural base pairs are identified that are both reasonably stable and strongly selective against mispairing with native bases. These results expand the potential nucleobase analogues with which the genetic alphabet may be expanded to include five-membered-ring heterocycles.
Cationic Liposome-MediatedE1AGene Transfer to Human Breast and Ovarian Cancer Cells and Its Biologic Effects: A Phase I Clinical Trial (2001)

These results argue for the feasibility of intracavitary DCC-E1A administration, provide a clear proof of preclinical concept, and warrant phase II trials to determine the antitumor activity of the E1A gene.
Applications of NADH-Dependent Fluorescence Sensors for Monitoring and Controlling Bioprocesses (2020)

Many biological compound such as proteins, enzymes, coenzymes, pigments, and primary or secondary metabolites emit characteristic fluorescence light after excitation by light from the visible or near-UV region. Among these compounds, reduced nicotinamide adenine dinucleotide (NADH) and reduced nicotinamide adenine di-nucleotide phosphate (NADPH) are the most important, since they are present in all living cells and play an important role in the microbial energy metabolism. NADH-dependent fluorescence can therefore be used to monitor biological compounds. This chapter focuses on the development and application of NADH-based sensors for quantifying the cell concentration and monitoring their metabolic state and for determining specific compounds that could be of interest in a biological process. Use of NADH-dependent sensors in control of bioprocesses is also discussed. Culture fluorescence has been proven as an index of biomass concentration even though a quantitation in terms of fluorescence per cell is yet to be established.
Treatment of restless legs syndrome: Evidence‐based review and implications for clinical practice (Revised 2017)§ (2018)

The objective of the current review was to update the previous evidence-based medicine review of treatments for restless legs syndrome published in 2008. All randomized, controlled trials (level I) with a high quality score published between January 2007 and January 2017 were reviewed. Forty new studies qualified for efficacy review. Pregabalin, gabapentin enacarbil, and oxycodone/naloxone, which did not appear in the previous review, have accrued data to be considered efficacious. Likewise, new data enable the modification of the level of efficacy for rotigotine from likely efficacious to efficacious. Intravenous ferric carboxymaltose and pneumatic compression devices are considered likely efficacious in idiopathic restless legs syndrome. Bupropion and clonidine were reviewed, but the lack of data determined a rating of insufficient evidence for efficacy. The following interventions continue to be considered efficacious as in 2008: levodopa, ropinirole, pramipexole, cabergoline, pergolide, and gabapentin. Bromocriptine, oxycodone, carbamazepine, and valproic acid are considered likely efficacious. Oral iron is nonefficacious in iron-sufficient subjects, but its benefit for patients with low peripheral iron status has not been adequately evaluated. Restless legs syndrome augmentation has been identified as a significant long-term treatment complication for pramipexole more than pregabalin and possibly for all dopaminergic agents more than α2δ ligands. Therefore, special monitoring for augmentation is required for all dopaminergic medications as well as tramadol. Other drugs also require special safety monitoring: cabergoline, pergolide, oxycodone, methadone, tramadol, carbamazepine, and valproic acid. Finally, we also highlighted gaps and needs for future clinical research and studies of restless legs syndrome. © 2018 International Parkinson and Movement Disorder Society.
Proliferative Defect and Embryonic Lethality in Mice Homozygous for a Deletion in the p110α Subunit of Phosphoinositide 3-Kinase (1999)

Phosphatidylinositol 3,4,5-trisphosphate is a phospholipid signaling molecule involved in many cellular functions including growth factor receptor signaling, cytoskeletal organization, chemotaxis, apoptosis, and protein trafficking. Phosphorylation at the 3 position of the inositol ring is catalyzed by many different 3-kinases (classified as types IA, IB, II, and III), but the physiological roles played by each of the different 3-kinase isozymes during embryonic development and in homeostasis in animals is incompletely understood. Mammalian type IA kinase isozymes are heterodimers that are active at 37 degrees C when the catalytic 110-kDa subunit interacts through an amino-terminal binding domain with a regulatory 85- or 55-kDa subunit. Using gene targeting in embryonic stem cells, we deleted this binding domain in the gene encoding the alpha isoform of the 110-kDa catalytic subunit (Pik3ca) of the alpha isozyme of the type IA kinases, leading to loss of expression of the p110 catalytic subunit. We show that Pik3cadel/del embryos are developmentally delayed at embryonic day (E) 9.5 and die between E9.5 and E10.5. E9. 5 Pik3cadel/del embryos have a profound proliferative defect but no increase in apoptosis. A proliferative defect is supported by the observation that fibroblasts from Pik3cadel/del embryos fail to replicate in Dulbecco's modified Eagle's medium and fetal calf serum, even with supplemental growth factors.
A Closed-Loop Artificial Pancreas Using Model Predictive Control and a Sliding Meal Size Estimator (2009)

The objective of this article is to present a comprehensive strategy for a closed-loop artificial pancreas. A meal detection and meal size estimation algorithm is developed for situations in which the subject forgets to provide a meal insulin bolus. A pharmacodynamic model of insulin action is used to provide insulin-on-board constraints to explicitly include the future effect of past and currently delivered insulin boluses. In addition, a supervisory pump shut-off feature is presented to avoid hypoglycemia. All of these components are used in conjunction with a feedback control algorithm using model predictive control (MPC). A model for MPC is developed based on a study of 20 subjects and is tested in a hypothetical clinical trial of 100 adolescent and 100 adult subjects using a Food and Drug Administration-approved diabetic subject simulator. In addition, a performance comparison of previously and newly proposed meal size estimation algorithms using 200 in silico subjects is presented. Using the new meal size estimation algorithm, the integrated artificial pancreas system yielded a daily mean glucose of 138 and 132 mg/dl for adolescents and adults, respectively, which is a substantial improvement over the MPC-only case, which yielded 159 and 145 mg/dl.
The purinergic P2Z receptor of human macrophage cells. Characterization and possible physiological role. (1995)

We have investigated responses of human monocyte/macrophage cells to extracellular ATP (ATPe). Freshly isolated peripheral blood monocytes showed responses linked to P2Y but not P2Z purinergic receptors; however, during in vitro macrophage differentiation, these cells also exhibited responses suggestive of the presence of the membrane-permeabilizing P2Z receptor. In fact, in human macrophages a brief (15-min) exposure to ATPe, but not other nucleotides, caused (1) a rapid and long-lasting plasma membrane depolarization; (2) a large increase in intracellular Ca2+ concentration followed by efflux of the Ca2+ indicator; (3) uptake of low molecular weight hydrophilic molecules such as Lucifer yellow and ethidium bromide; and (4) cell rounding, swelling, and eventual release of the cytoplasmic enzyme lactate dehydrogenase. rIFN-gamma enhanced both membrane-permeabilizing and cytotoxic ATPe effects. Membrane permeabilization and cytotoxicity were fully blocked by pretreatment of the cells with oxidized ATP, a compound recently shown to block P2Z receptors covalently in macrophages. Blocking of the P2Z receptor by oxidized ATP also inhibited multinucleated giant cell generation stimulated by concanavalin A or rIFN-gamma without decreasing monocyte migration or membrane adhesion molecule expression. These data suggest that human macrophages express rIFN-gamma-modulated purinergic P2Z receptors in vitro and hint at a role for these plasma membrane molecules in the generation of macrophage polykarions.
A 2.4 kbit/s MELP coder candidate for the new U.S. Federal Standard (2002)

This paper describes our enhanced mixed excitation linear prediction (MELP) speech coder which is a candidate for the new U.S. Federal Standard at 2.4 kbits/s. The new coder is based on the MELP model, and it uses a number of enhancements as well as efficient quantization algorithms to improve performance while maintaining a low bit rate. In addition, the coder has been optimized for performance in acoustic background noise and in channel errors, as well as for efficient real-time implementation. Listening tests confirm that the enhanced 2.4 kbit/s MELP coder performs as well as the higher bit rate 4.8 kbit/s FS1016 CELP standard.
Leaky-Wave Theory, Techniques, and Applications: From Microwaves to Visible Frequencies (2015)

Leaky waves have been among the most active areas of research in microwave engineering over the second half of the 20th century. They have been shown to dominate the near-field of several open wave-guiding structures, of great interest to tailor their radiation, guidance and filtering properties. The elegant theoretical analyses and deep physical insights in this area, developed in an era in which computational resources were limited, represent a fundamental scientific legacy that is still extremely relevant in today's engineering society and beyond. In this regard, the relevance of leaky-wave concepts has been increasingly recognized in recent times over a broader scientific community, including optics and physics societies. In this paper, after revisiting the fundamental concepts of leaky-wave theory, we discuss and connect different relevant research activities in which leaky-wave concepts have been applied, with the goal of facilitating multidisciplinary interactions on these topics. In addition to the canonical microwave applications of leaky waves, particular attention is devoted to a few areas of interest in modern optics, such as directive optical antennas, extraordinary optical transmission, and embedded scattering eigenvalues, in which leaky waves play a fundamental role.
Synthesis and Preliminary Biological Evaluation of High-Drug-Load Paclitaxel-Antibody Conjugates for Tumor-Targeted Chemotherapy (2009)

The goal of this study was to design paclitaxel (PTX)-monoclonal antibody (mAb) prodrug conjugates (PTXMAbs) with the ability to deliver therapeutically significant doses of the drug to the tumor while avoiding the previously observed solubility limitations of conjugates with PTX:mAb molar ratios of >3. New PTX conjugates were synthesized using the discrete poly(ethylene glycol) (dPEG) as linkers. These compounds, PTX-L-Lys[(dPEG12)(3)-dPEG4]-dPEG6-NHS (9a and 9b, for L = GL or SX, respectively), were then conjugated to the antiepidermal growth factor receptor mAb, C225 at increasing PTX:C225 ratios, producing completely soluble conjugates. Unlike the earlier PTXMAbs, buffered solutions of these conjugates remained homogeneous for extended periods of time. Fluorescence-activated cell sorting (FACS) analysis indicated preserved immunogenicity of the conjugates at all four substitution ratios, while cytotoxicity studies in MDA-MB-468 breast cancer cells indicated preservation of drug cytotoxicity. These conjugates may have potential in the development of high-drug-load tumor-targeting taxanes.
VEGF165 promotes survival of leukemic cells by Hsp90-mediated induction of Bcl-2 expression and apoptosis inhibition (2002)

Similar to endothelial cells (ECs), vascular endothelial growth factor (VEGF) induces Bcl-2 expression on VEGF receptor-positive (VEGFR(+)) primary leukemias and cell lines, promoting survival. We investigated the molecular pathways activated by VEGF on such leukemias, by performing a gene expression analysis of VEGF-treated and untreated HL-60 leukemic cells. One gene to increase after VEGF stimulation was heat shock protein 90 (Hsp90). This was subsequently confirmed at the protein level, on primary leukemias and leukemic cell lines. VEGF increased the expression of Hsp90 by interacting with KDR and activating the mitogen-activated protein kinase cascade. In turn, Hsp90 modulated Bcl-2 expression, as shown by a complete blockage of VEGF-induced Bcl-2 expression and binding to Hsp90 by the Hsp90-specific inhibitor geldanamycin (GA). GA also blocked the VEGF-induced Hsp90 binding to APAF-1 on leukemic cells, a mechanism shown to inhibit apoptosis. Notably, VEGF blocked the proapoptotic effects of GA, correlating with its effects at the molecular level. Earlier, we showed that in some leukemias, a VEGF/KDR autocrine loop is essential for cell survival, whereas here we identified the molecular correlates for such an effect. We also demonstrate that the generation of a VEGF/VEGFR autocrine loop on VEGFR(+) cells such as ECs, also protected them from apoptosis. Infection of ECs with adenovirus-expressing VEGF resulted in elevated Hsp90 levels, increased Bcl-2 expression, and resistance to serum-free or GA-induced apoptosis. In summary, we demonstrate that Hsp90 mediates antiapoptotic and survival-promoting effects of VEGF, which may contribute to the survival advantage of VEGFR(+) cells such as subsets of leukemias.
Repellent Signaling by Slit Requires the Leucine-Rich Repeats (2001)

Slit is a repellent axon guidance cue produced by the midline glia in Drosophila that is required to regulate the formation of contralateral projections and the lateral position of longitudinal tracts. Four sequence motifs comprise the structure of Slit: a leucine-rich repeat (LRR), epidermal growth factor-like (EGF) repeats, a laminin-like globular (G)-domain, and a cysteine domain. Here we demonstrate that the LRR is required for repellent signaling and in vitro binding to Robo. Repellent signaling by slit is reduced by point mutations that encode single amino acid changes in the LRR domain. By contrast to the EGF or G-domains, the LRR domain is required in transgenes to affect axon guidance. Finally, we show that the midline repellent receptor, Robo, binds Slit proteins with internal deletions that also retain repellent activity. However, Robo does not bind Slit protein missing the LRR. Taken together, our data demonstrate that Robo binding and repellent signaling by Slit require the LRR region.
Post-Self-Assembly Cross-Linking of Molecular Nanofibers for Oscillatory Hydrogels (2012)

After a polymerizable hydrogelator self-assembles in water to form molecular nanofibers, post-self-assembly cross-linking allows the catalyst of the Belousov-Zhabotinsky (BZ) reaction to be attached to the nanofibers, resulting in a hydrogel that exhibits concentration oscillations, spiral waves, and concentric waves. In addition to the first report of the observation of BZ spiral waves in a hydrogel that covalently integrates the catalyst, we suggest a new approach to developing active soft materials as chemical oscillators and for exploring the correlation between molecular structure and far-from-equilibrium dynamics.