gebhart/patrepeval huggingface dataset:
Molecular cloning of a 47 kda tissue-specific and differentiationdependent urothelial cell surface glycoprotein (1993)

Despite the fact that bladder epithelium has many interesting biological features and is a frequent site of carcinoma formation, relatively little is known about its biochemical differentiation. We have shown recently that a 47 kDa glycoprotein, uroplakin III (UPIII), in conjunction with uroplakins I (27 kDa) and II (15 kDa), forms the asymmetric unit membrane (AUM)--a highly specialized biomembrane characteristic of the apical surface of bladder epithelium. Deglycosylation and cDNA sequencing revealed that UPIII contains up to 20 kDa of N-linked sugars attached to a core protein of 28.9 kDa. The presence of an N-terminal signal peptide sequence and a single transmembrane domain located near the C terminus, plus the N-terminal location of all the potential N-glycosylation sites, points to a type I (N-exo/C-cyto) configuration. Thus the mass of the extracellular domain (20 kDa plus up to 20 kDa of sugar) of UPIII greatly exceeds that of its intracellular domain (5 kDa). Such an asymmetrical mass distribution, a feature shared by the other two major uroplakins, provides a molecular explanation as to why the luminal leaflet of AUM is almost twice as thick as the cytoplasmic one. The fact that of the three major proteins of AUM only UPIII has a significant cytoplasmic domain suggests that this molecule may play an important role in AUM-cytoskeleton interaction in terminally differentiated urothelial cells.
Interaction between EGFR signaling and DE-cadherin during nervous system morphogenesis (2002)

Dynamically regulated cell adhesion plays an important role during animal morphogenesis. Here we use the formation of the visual system in Drosophila embryos as a model system to investigate the function of the Drosophila classic cadherin, DE-cadherin, which is encoded by the shotgun (shg) gene. The visual system is derived from the optic placode which normally invaginates from the surface ectoderm of the embryo and gives rise to two separate structures, the larval eye (Bolwig's organ) and the optic lobe. The optic placode dissociates and undergoes apoptotic cell death in the absence of DE-cadherin, whereas overexpression of DE-cadherin results in the failure of optic placode cells to invaginate and of Bolwig's organ precursors to separate from the placode. These findings indicate that dynamically regulated levels of DE-cadherin are essential for normal optic placode development. It was shown previously that overexpression of DE-cadherin can disrupt Wingless signaling through titration of Armadillo out of the cytoplasm to the membrane. However, the observed defects are likely the consequence of altered DE-cadherin mediated adhesion rather than a result of compromising Wingless signaling, as overexpression of a DE-cadherin-alpha-catenin fusion protein, which lacks Armadillo binding sites, causes similar defects as DE-cadherin overexpression. We further studied the genetic interaction between DE-cadherin and the Drosophila EGF receptor homolog, EGFR. If EGFR function is eliminated, optic placode defects resemble those following DE-cadherin overexpression, which suggests that loss of EGFR results in an increased adhesion of optic placode cells. An interaction between EGFR and DE-cadherin is further supported by the finding that expression of a constitutively active EGFR enhances the phenotype of a weak shg mutation, whereas a mutation in rhomboid (rho) (an activator of the EGFR ligand Spitz) partially suppresses the shg mutant phenotype. Finally, EGFR can be co-immunoprecipitated with anti-DE-cadherin and anti-Armadillo antibodies from embryonic protein extracts. We propose that EGFR signaling plays a role in morphogenesis by modulating cell adhesion.
The OECD program to validate the rat uterotrophic bioassay to screen compounds for in vivo estrogenic responses: phase 1. (2001)

The Organisation for Economic Co-operation and Development has completed the first phase of an international validation program for the rodent uterotrophic bioassay. This uterotrophic bioassay is intended to identify the in vivo activity of compounds that are suspected agonists or antagonists of estrogen. This information could, for example, be used to help prioritize positive compounds for further testing. Using draft protocols, we tested and compared two model systems, the immature female rat and the adult ovariectomized rat. Data from 19 participating laboratories using a high-potency reference agonist, ethinyl estradiol (EE), and an antagonist, ZM 189,154, indicate no substantive performance differences between models. All laboratories and all protocols successfully detected increases in uterine weights using EE in phase 1. These significant uterine weight increases were achieved under a variety of experimental conditions (e.g., strain, diet, housing protocol, bedding, vehicle). For each protocol, there was generally good agreement among laboratories with regard to the actual EE doses both in producing the first significant increase in uterine weights and achieving the maximum uterine response. Furthermore, the Hill equation appears to model the dose response satisfactorily and indicates general agreement based on calculated effective dose (ED)(10) and ED(50) within and among laboratories. The feasibility of an antagonist assay was also successfully demonstrated. Therefore, both models appear robust, reproducible, and transferable across laboratories for high-potency estrogen agonists such as EE. For the next phase of the OECD validation program, both models will be tested against a battery of weak, partial estrogen agonists.
MONITORING GRASSLANDS USING CONVEX GEOMETRY AND PARTIAL UNMIXING - A CASE STUDY (1998)

The main purpose of the study was to investigate if convex geometry and partial unmixing could be used to map succession stages on grasslands with respect to encroachment. The study was performed on a Compact Airborne Spectrographic Imager (casi) image acquired in 2 m resolution spatial mode with 11 bands in the spectral range from 396.2-902.6 nm. Spectral mode image data was used to assess the radiometric and spectral calibration and consequently the spatial data was spatially and spectrally subset to include 9 bands. The data were calibrated to surface reflectance and transformed to minimum noise fraction (MNF) feature space and the spectral dimensionality of the data was evaluated. Pixel purity indexing (PPI) technique was used to extract the purest pixels in the image from convex geometry concepts and rotating three-dimensional scatterplots were used to find endmember related to woody species. Two endmembers were identified: deciduous trees and conifers. Conifers were highly correlated with shade. Matched filtering or Constrained Energy Minimization (CEM) was used to map the selected endmembers. Forests with deciduous trees and conifers had high abundance. Groups of trees on derelict grassland areas where the density and age of trees were similar to the forests also had high abundance. Individual woody species out in the open grassland area had high abundance in a few places. Grassland areas with a spectral signature similar to conifers came out with low abundance and agricultural fields came out as false positives. It is generally concluded that the image gives the option of mapping succession at a late encroachment stage whereas individual scrubs at early encroachment stages tend to be overlooked.
Combined Expression of Pancreatic Duodenal Homeobox 1 and Islet Factor 1 Induces Immature Enterocytes to Produce Insulin (2002)

Immature rat intestinal stem cells (IEC-6) given the ability to express the transcription factor, pancreatic duodenal homeobox 1 (Pdx-1), yielded YK cells. Although these cells produced multiple enteroendocrine hormones, they did not produce insulin. Exposure of YK cells to 2 nmol/l betacellulin yielded BYK cells that showed the presence of insulin expression in cytoplasm and that secreted insulin into culture media. By examining the mechanism of differentiation in BYK cells, we found that another transcription factor, islet factor 1 (Isl-1) was newly expressed with the disappearance of Pax-6 expression in those cells after exposure to betacellulin. These results indicated that combined expression of Pdx-1 and Isl-1 in IEC-6 cells was required for the production of insulin. In fact, overexpression of both Pdx-1 and Isl-1 in IEC-6 cells (Isl-YK-12, -14, and -15 cells) gave them the ability to express insulin without exposure to betacellulin. Furthermore, implantation of the Isl-YK-14 cells into diabetic rats reduced the animals' plasma glucose levels; glucose levels dropped from 19.4 to 16.9 mmol/l 1 day after the injection of cells. As expected, the plasma insulin concentrations were 2.7 times higher in the diabetic rats injected with Isl-YK-14 cells compared to in controls. In summary, our results indicated that immature intestinal stem cells can differentiate into insulin-producing cells given the ability to express the transcription factors Pdx-1 and Isl-1.
Identification of effector residues and a neutralizing epitope of Ha-ras-encoded p21. (1986)

To identify the amino acid residues of the Harvey (Ha) ras-encoded protein that are involved in protein-protein interactions, we have created a series of mutant Ha-ras proteins. In particular, amino acid substitutions have been introduced within two regions, residues 32-42 and 61-80, that are conserved among ras proteins from different species. We observed that amino acid substitutions at positions 35, 36, 38, 40, and, to a lesser extent, 39 and 78 reduce the biological potency of Ha-ras protein in both mammalian and Saccharomyces cerevisiae cells, without noticeably affecting the known intrinsic biochemistry of these proteins. The reduction of in vivo activity for these mutant ras proteins correlates with their reduced ability to stimulate yeast adenylate cyclase. The ras-protein-neutralizing antibody Y13-259 binds to six residues: Glu-63, Ser-65, Ala-66, Met-67, Gln-70, and Arg-73. Single substitutions for these residues reduce Y13-259 antibody binding by at least a factor of 1000 but do not significantly affect biological activity. These data are discussed in terms of the model for Ha-ras protein based on the structure of the elongation factor EF-Tu-GDP complex.
Early commitment of naïve human CD4+ T cells to the T follicular helper (TFH) cell lineage is induced by IL‐12 (2009)

T follicular helper (T(FH)) cells are a specialized subset of CD4(+) T cells that localize to B-cell follicles, where they are positioned to provide help for the induction of optimal humoral immune responses. Key features of T(FH) cells are the expressions of CXCR5, ICOS, interleukin (IL)-21 and BCL-6. The requirements for human T(FH) cell development are unknown. Here we show that IL-6, IL-12, IL-21 and IL-23 are capable of inducing IL-21 expression in naïve CD4(+) T cells isolated from human tonsils, peripheral blood and cord blood. However, only IL-12 induced sustained expressions of CXCR5 and ICOS on these activated naïve CD4(+) T cells, and endowed them with the ability to provide increased help to B cells for their differentiation into immunoglobulin-secreting cells. The effects of IL-12 were independent of interferon-gamma and T-bet, and associated with upregulation of BCL-6 expression. Thus, these cytokines, particularly IL-12, are likely to act at an early stage during dendritic cell-mediated priming of naïve CD4(+) T cells into a T(FH) cell fate, and thus underpin antibody-mediated immunity.
<title>Consistent debiased method for converting between polar and Cartesian coordinate systems</title> (1997)

A significant problem in tracking and estimation is the consistent transformation of uncertain state estimates between Cartesian and spherical coordinate systems. For example, a radar system generates measurements in its own local spherical coordinate system. In order to combine those measurements with those from other radars, however, a tracking system typically transforms all measurements to a common Cartesian coordinate system. The most common approach is to approximate the transformation through linearization. However, this approximation can lead to biases and inconsistencies, especially when the uncertainties on the measurements are large. A number of approaches have been proposed for using higher order transformation modes, but these approaches have found only limited use due to the often enormous implementation burdens incurred by the need to derive Jacobians and Hessians. This paper expands a method for nonlinear propagation which is described in a companion paper. A discrete set of samples are used to capture the first four moments of the untransformed measurement. The transformation is then applied to each of the samples, and the mean and covariance are calculated from the result. It is shown that the performance of the algorithm is comparable to that of fourth order filters, thus ensuring consistency even when the uncertainty is large. It is not necessary to calculate any derivatives, and the algorithm can be extended to incorporate higher order information. The benefits of this algorithm are illustrated in the contexts of autonomous vehicle navigation and missile tracking.
Regulation of Ocular Angiogenesis by Notch Signaling: Implications in Neovascular Age-Related Macular Degeneration (2011)

This study suggests that Notch signaling is a key regulator of CNV and thus a molecular target for therapeutic intervention in wet AMD.
THE VASCULAR BIOLOGY OF NITRIC OXIDE AND ITS ROLE IN ATHEROGENESIS (1996)

Nitric oxide (NO), the biologically active component of endothelium-derived relaxing factor, has critical roles in the maintenance of vascular homeostasis. Decreased endothelial NO production, as a result of endothelial dysfunction, occurs in the early phases of atherosclerosis. NO appears to inhibit atherogenesis by inhibiting leukocyte and platelet activation and by inhibiting smooth muscle cell proliferation. Endothelial denudation is a prominent feature of vascular injury associated with percutaneous angioplasty, and decreased NO production appears to contribute to the restenosis process. Manipulation of the NO/cGMP signal transduction system may provide novel therapeutic approaches for limiting atherogenesis and neointimal proliferation in the future.
A Wideband 3.6 GHz Digital ΔΣ Fractional-N PLL With Phase Interpolation Divider and Digital Spur Cancellation (2011)

A digital ΔΣ fractional-N frequency synthesizer for 4G communication standards is presented which is able to achieve wide loop bandwidth while producing low fractional spurs. The loop adopts a fractional-N divider based on a phase interpolator, allowing to shrink the TDC dynamic range and to improve its linearity. A dynamic-element matching algorithm is employed to further improve TDC linearity and an original correlation algorithm is used to correct for the phase interpolator mismatches. Both digital algorithms operate in background and they are demonstrated to be concurrently effective in reducing in-band fractional spurs below -57 dBc. The circuit is fully integrated in a 65 nm CMOS process and it synthesizes a carrier in the 3.0-3.6 GHz range from a 40 MHz crystal reference with 40 Hz resolution. It achieves -104-dBc/Hz phase noise at 400-kHz offset and a 3.2-MHz maximum loop bandwidth. The synthesizer dissipates 80 mW and occupies 0.4 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> .
Automated Method for Tracking Vast Numbers of FITC‐Labeled RBCs in Microvessels of Rat Brain In Vivo Using a High‐Speed Confocal Microscope System (2008)

High-speed camera investigation of rapidly moving red blood cells (RBCs) in the microvasculature has been limited by an inability to handle the vast volume of data. We have developed a novel method to analyze large numbers of RBC images captured by a high-resolution, high-speed camera fitted on a confocal fluorescence microscope, to determine the velocities of individual RBCs in capillaries in vivo. Fluorescein isothiocyanate (FITC)-labeled RBCs flowing in the microvasculature of the cerebral cortex of urethane-anesthetized Wistar rats were recorded through the skull window on video clips during specified periods at high frame rates (500 fps). Sequential frames of moving RBCs in the video clips for a specified period were analyzed offline with in-house software (KEIO-IS2). Images of RBCs acquired were numbered automatically in order of appearance and displayed in a two-dimensional (2-D) RBC tracking map. The velocities of individual RBCs were automatically computed based on the RBC displacement per frame multiplied by the frame rate (fps), and the results were displayed in a 2-D velocity map and a 2-D RBC number map. Single capillaries were identified by staining with FITC-dextran. The mean capillary velocity of RBCs was evaluated as 2.05 +/- 1.59 mm/second in video clips obtained at 500 fps. This method is considered to have wide potential applicability.
A Review of Complications of Amphotericin-B Therapy: Recommendations for Prevention and Management (1980)

The pathogenesis, clinical manifestations, and management of adverse reactions of amphotericin B are presented. Various types of nephrotoxicity, thrombophlebitis, and anemia are described along with suggestions for their prevention and management. The management of generalized reactions such as fever, GI upset, headache, and myalgias is discussed, along with a commentary on allergic reactions. Complications associated with intrathecal administration and aerosolization of the drug are also described.
Synthesis of D‐Desosamine and Analogs by Rapid Assembly of 3‐Amino Sugars (2015)

D-Desosamine is synthesized in 4 steps from methyl vinyl ketone and sodium nitrite. The key step in this chromatography-free synthesis is the coupling of (R)-4-nitro-2-butanol and glyoxal (trimeric form) mediated by cesium carbonate, which affords in crystalline form 3-nitro-3,4,6-trideoxy-α-D-glucose, a nitro sugar stereochemically homologous to D-desosamine. This strategy has enabled the syntheses of an array of analogous 3-nitro sugars. In each case the 3-nitro sugars are obtained in pure form by crystallization.
Toll-like receptors and their ligands control mesenchymal stem cell functions (2006)

Mesenchymal stem cells (MSCs) are widespread in adult organisms and may be involved in tissue maintenance and repair as well as in the regulation of hematopoiesis and immunologic responses. Thus, it is important to discover the factors controlling MSC renewal and differentiation. Here we report that adult MSCs express functional Toll-like receptors (TLRs), confirmed by the responses of MSCs to TLR ligands. Pam3Cys, a prototypic TLR-2 ligand, augmented interleukin-6 secretion by MSC, induced nuclear factor kappa B (NF-kappaB) translocation, reduced MSC basal motility, and increased MSC proliferation. The hallmark of MSC function is the capacity to differentiate into several mesodermal lineages. We show herein that Pam3Cys inhibited MSC differentiation into osteogenic, adipogenic, and chondrogenic cells while sparing their immunosuppressive effect. Our study therefore shows that a TLR ligand can antagonize MSC differentiation triggered by exogenous mediators and consequently maintains the cells in an undifferentiated and proliferating state in vitro. Moreover, MSCs derived from myeloid factor 88 (MyD88)-deficient mice lacked the capacity to differentiate effectively into osteogenic and chondrogenic cells. It appears that TLRs and their ligands can serve as regulators of MSC proliferation and differentiation and might affect the maintenance of MSC multipotency.
Nucleic acid and structural proteins of infectious bursal disease virus isolates belonging to serotypes I and II. (1985)

The nucleic acid and structural proteins of infectious bursal disease virus serotype I (six isolates) were compared with those of serotype II (two isolates). Five of the serotype I isolates originated from chickens, whereas both serotype II isolates were from turkeys. The growth curves of representative isolates of both serotypes were similar, but the latent period and virus yield were different. The seven isolates tested had two segments of double-stranded genomic RNA. The RNA migration patterns of viruses belonging to each serotype were similar, but differences were noticed between the two serotypes. There were differences in the molecular weights of viral proteins (VP) 3 and 4 from the two serotypes, and serotype II isolates lacked VP-2.
Osteobiologics. (2004)

"Osteobiologics" is the term that has been introduced to refer to the class of engineered materials that have been created and which promote healing of fractures and bone defects. The list of osteobiologics is rapidly expanding as new products incorporating osteoconductive materials are mixed with a variety of osteoinductive proteins, demineralized bone, and preparations of osteogenic cells. The growth in osteobiologics has been stimulated by the early success of osteoconductive materials as graft substitutes in the repair of fractures and by the increasing demand for grafts in all areas of orthopaedics. Although allografts have historically been employed with success, the number of donors has grown much slower than demand leading to the development of artificial materials. Manufactured bone graft substitutes, or osteobiologics, attempt to mimic the components of an autogeneous bone graft by reproducing the bone matrix, which is osteoconductive and osteoinductive. Other products aim to introduce osteogenic cells by concentrating bone marrow while others introduce differing growth factors from platelets in peripheral blood. Very few of these products have been supported by appropriate clinical studies and as such their value is unknown. Orthopaedic surgeons employing these products must understand the basic science principles behind their development in order to understand the indications and limitations of their application. Properly designed clinical studies should be performed to determine the usefulness and cost-effectiveness of both current and future products.
Cell-free DNA Fragmentation Patterns in Amniotic Fluid Identify Genetic Abnormalities and Changes due to Storage (2008)

Circulating cell-free DNA (cfDNA) has become a promising biomarker in prenatal diagnosis. However, despite extensive studies in different body fluids, cfDNA predictive value is uncertain owing to the confounding factors that can affect its levels, such as gestational age, maternal weight, smoking status, and medications. Residual fresh and archived amniotic fluid (AF) supernatants were obtained from gravid women (mean gestational age 17 wk) carrying euploid (N=36) and aneuploid (N=29) fetuses, to characterize cfDNA-fragmentation patterns with regard to aneuploidy and storage time (-80 degrees C). AF cfDNA was characterized by the real-time quantitative polymerase chain reaction amplification of glyceraldehyde-3-phosphate dehydrogenase, gel electrophoresis, and pattern recognition of the DNA fragmentation. The distributions of cfDNA fragment lengths were compared using 6 measures that defined the locations and slopes for the first and last peaks, after elimination of the confounding variables. This method allowed for the unique classification of euploid and aneuploid cfDNA samples in AF, which had been matched for storage time. In addition, we showed that archived euploid AF samples gradually lose long cfDNA fragments: this loss accurately distinguishes them from the fresh samples. We present preliminary data using cfDNA-fragmentation patterns, to uniquely distinguish between AF samples of pregnant women with regard to aneuploidy and storage time, independent of gestational age and initial DNA amount. In addition to potential applications in prenatal diagnosis, these data suggest that archived AF samples consist of large amounts of short cfDNA fragments, which are undetectable using standard real-time polymerase chain reaction amplification.