gebhart/patrepeval huggingface dataset:
Harnessing the Immune System for Treatment and Detection of Tau Pathology (2014)

The tau protein is an attractive target for therapy and diagnosis. We started a tau immunotherapy program about 13 years ago and have since demonstrated that active and passive immunotherapies diminish tau pathology and improve function, including cognition, in different mouse models. These findings have been confirmed and extended by several groups. We routinely detect neuronal, and to a lesser extent microglial, antibody uptake correlating with tau pathology. Antibodies bind tau aggregates in the endosomal/lysosomal system, enhancing clearance presumably by promoting their disassembly. Extracellular clearance has recently been shown by others, using antibodies that apparently are not internalized. As most pathological tau is neuronal, intracellular targeting may be more efficacious. However, extracellular tau may be more accessible to antibodies, with tau-antibody complexes a target for microglial phagocytosis. The extent of involvement of each pathway may depend on numerous factors including antibody properties, degree of pathology, and experimental model. On the imaging front, multiple tau ligands derived from β-sheet dyes have been developed by several groups, some with promising results in clinical PET tests. Postmortem analysis should clarify their tau specificity, as in theory and based on histological staining, those are likely to have some affinity for various amyloids. We are developing antibody-derived tau probes that should be more specific, and have in mouse models shown in vivo detection and binding to pathological tau after peripheral injection. These are exciting times for research on tau therapies and diagnostic agents that hopefully can be applied to humans in the near future.
Semiconductor laser array in an external Talbot cavity (1992)

This paper describes semiconductor laser arrays placed in an external Talbot cavity. The external Talbot cavity couples the light between many adjacent lasers such that all lasers operate at the same frequency and phase, resulting in a high power diffraction limited output beam. We designed a compact cavity which is comprised of a 30 by 50 element monolithic 2-D laser array, a GaP mass transport lens array, a liquid crystal array, a phase sensing and control system and a waveguide. Initial results obtained from a 20 element linear Ta1bOt cavity with a calculated mode discrimination similar to the 2-D cavity demonstrate in excess of 30 mW cw per laser element in a diffraction limited far field. In addition we have also demonstrated 50 Watt CW incoherent output power from a monolithic 2D laser array
Lipid Metabolism and Liver Inflammation. I. Hepatic fatty acid uptake: possible role in steatosis (2006)

Hepatic steatosis is a growing public health concern. Nonalcoholic fatty liver is increasingly common in Western societies and may lead to steatohepatitis, fibrosis, and cirrhosis, possibly triggered by lipid peroxidation. The relation of fatty liver to obesity, type II diabetes, and/or metabolic syndrome is significant. One aspect these related disorders share is increased serum-free fatty acids, which may be taken up by hepatocytes. Uptake of fatty acids in excess of metabolic requirements will lead to storage as triglycerides, resulting in steatosis and providing substrate for lipid peroxidation. Fatty acid uptake may be crucial to understanding steatosis.
Design and analysis of frame-based fair queueing (1996)

In this paper we introduce and analyze frame-based fair queueing , a novel traffic scheduling algorithm for packet-switched networks. The algorithm provides end-to-end delay bounds identical to those of PGPS (packet-level generalized processor sharing), without the complexity of simulating the fluid-model system in the background as required in PGPS. The algorithm is therefore ideally suited for implementation in packet switches supporting a large number of sessions. We present a simple implementation of the algorithm for a general packet switch. In addition, we prove that the algorithm is fair in the sense that sessions are not penalized for excess bandwidth they received while other sessions were idle. Frame-based fair queueing belongs to a general class of scheduling algorithms, which we call Rate-Proportional Servers . This class of algorithms provides the same end-to-end delay and burstiness bounds as PGPS, but allows more flexibility in the design and implementation of the algorithm. We provide a systematic analysis of this class of schedulers and obtain bounds on their fairness.
Fully automatic matching of circular markers for camera calibration (2008)

Camera calibration is one of critical steps in computer vision, also an exhaustive process because substantial human computer interactions are frequently required to deal with the matching problem. In this paper, an automatic matching method of markers for camera calibration is presented based on the local architecture characteristics of a new planar circle pattern, which can be applied to a wide range of spoiled images including those of distortion, noise, and blur. Firstly, a robust ellipse detector is developed to extract ellipses from the image. After the centroids of the ellipses are triangulated into triangle network by Delaunay method to find k annular neighborhood of each ellipse, a cost function is defined to locate orientation ellipses for the homography matrix between the image and the calibration pattern. Then the correspondences between the marker ellipses and the marker circles are established by a homography method followed by a point sets registration strategy. Finally, the method is tested with real and transformed images to show its accuracy and robustness, which is entirely unsupervised and easily embedded into the exiting algorithms
Emerging synthetic approaches for protein–polymer conjugations (2011)

Protein-polymer conjugates are important in diverse fields including drug delivery, biotechnology, and nanotechnology. This feature article highlights recent advances in the synthesis and application of protein-polymer conjugates by controlled radical polymerization techniques. Special emphasis on new applications of the materials, particularly in biomedicine, is provided.
A Proof-of-Principle Clinical Trial of Bexarotene in Patients with Non–Small Cell Lung Cancer (2007)

Bexarotene represses proliferation and biomarker expression in responsive, but not resistant HBE and lung cancer cells. Similar biomarker changes occur in lung tumors when therapeutic intratumoral bexarotene levels are achieved. This proof-of-principle trial approach is useful to uncover pharmacodynamic mechanisms in vivo and relate these to intratumoral pharmacokinetic effects.
Mrp4 Confers Resistance to Topotecan and Protects the Brain from Chemotherapy (2004)

The role of the multidrug resistance protein MRP4/ABCC4 in vivo remains undefined. To explore this role, we generated Mrp4-deficient mice. Unexpectedly, these mice showed enhanced accumulation of the anticancer agent topotecan in brain tissue and cerebrospinal fluid (CSF). Further studies demonstrated that topotecan was an Mrp4 substrate and that cells overexpressing Mrp4 were resistant to its cytotoxic effects. We then used new antibodies to discover that Mrp4 is unique among the anionic ATP-dependent transporters in its dual localization at the basolateral membrane of the choroid plexus epithelium and in the apical membrane of the endothelial cells of the brain capillaries. Microdialysis sampling of ventricular CSF demonstrated that localization of Mrp4 at the choroid epithelium is integral to its function in limiting drug penetration into the CSF. The topotecan resistance of cells overexpressing Mrp4 and the polarized expression of Mrp4 in the choroid plexus and brain capillary endothelial cells indicate that Mrp4 has a dual role in protecting the brain from cytotoxins and suggest that the therapeutic efficacy of central nervous system-directed drugs that are Mrp4 substrates may be improved by developing Mrp4 inhibitors.
Antibiotic Susceptibility Determination within One Cell Cycle at Single-Bacterium Level by Stimulated Raman Metabolic Imaging (2018)

The widespread use of antibiotics has significantly increased the number of resistant bacteria, which has also increased the urgency of rapid bacterial detection and profiling their antibiotic response. Current clinical methods for antibiotic susceptibility testing (AST) rely on culture and require at least 16 to 24 h to conduct. Therefore, there is an urgent need for a rapid method that can test the susceptibility of bacteria in a culture-free manner. Here we demonstrate a rapid AST method by monitoring the glucose metabolic activity of live bacteria at the single-cell level with hyperspectral stimulated Raman scattering (SRS) imaging. Using vancomycin-susceptible and -resistant enterococci E. faecalis as models, we demonstrate that the metabolic uptake of deuterated glucose in a single living bacterium can be quantitatively monitored via hyperspectral SRS imaging. Remarkably, the metabolic activity of susceptible bacteria responds differently to antibiotics from the resistant strain within only 0.5 h from the addition of antibiotics. Therefore, bacterial susceptibility and the minimum inhibitory concentration (MIC) of antibiotics can be determined within one cell cycle. Our metabolic imaging method is applicable to other bacteria species including E. coli, K. Pneumoniae, and S. aureus as well as different antibiotics, regardless of their mechanisms of inhibiting or killing bacteria.
Gonadotropin-Independent Precocious Puberty Due to Luteinizing Hormone Receptor Mutations in Brazilian Boys: A Novel Constitutively Activating Mutation in the First Transmembrane Helix (2000)

Made available in DSpace on 2014-12-02T16:29:56Z (GMT). No. of bitstreams: 1 WOS000166277800060.pdf: 913762 bytes, checksum: 0acfa1038f4f30b85ba14e38bf9ab8d6 (MD5) Previous issue date: 2000
Release of Platelet-Activating Factor in Acute Experimental Pancreatitis (1993)

This study demonstrates the formation of platelet-activating factor (PAF) in rats with acute experimental pancreatitis (AEP). The AEP was induced by infusing sodium taurodeoxycholate and trypsin into the bile-pancreatic duct. The PAF content was increased in blood samples and in pulmonary and pancreatic tissue as compared with control animals. Significant amounts of PAF were also found in peritoneal fluid. The PAF content did increase in blood samples and in pulmonary tissue after administration of endotoxin intravenously. The effects of intraperitoneal PAF administration were also studied and showed an increase of polymorphonuclear cells in blood samples. These findings suggest that acute pancreatitis might generate and release PAF. Whether PAF release is associated with the pathophysiology of complications in acute pancreatitis remains to be elucidated.
Mononuclear myeloid-derived “suppressor” cells express RAE-1 and activate natural killer cells (2008)

Myeloid-derived suppressor cells (MDSCs) accumulate in cancer patients and tumor-bearing mice and potently suppress T-cell activation. In this study, we investigated whether MDSCs regu-late natural killer (NK)-cell function. We discovered that mononuclear Gr-1(+)CD11b(+)F4/80(+) MDSCs isolated from RMA-S tumor-bearing mice do not suppress, but activate NK cells to produce high amounts of IFN-gamma. Gr-1(+)CD11b(+)F4/80(+) MDSCs isolated from tumor-bearing mice, but not myeloid cells from naive mice, expressed the ligand for the activating receptor NKG2D, RAE-1. NK-cell activation by MDSCs depended partially on the interaction of NKG2D on NK cells with RAE-1 on MDSCs. NK cells eliminated Gr-1(+)CD11b(+)F4/80(+) MDSCs in vitro and upon adoptive transfer in vivo. Finally, depletion of Gr-1(+) cells that comprise MDSCs confirmed their protective role against the NK-sensitive RMA-S lymphoma in vivo. Our study reveals that MDSCs do not suppress all aspects of antitumor immune responses and defines a novel, unexpected activating role of MDSCs on NK cells. Thus, our results have great impact on the design of immune therapies against cancer aiming at the manipulation of MDSCs.
High-Mobility Field-Effect Transistors Based on Single-Crystalline ZnO Channels (2005)

We have fabricated field-effect transistors with single-crystalline ZnO channels consisting of high-quality epitaxial films grown on lattice-matched (0001) ScAlMgO 4 substrates by laser molecular-beam epitaxy. Amorphous alumina gate insulators are deposited on the top of the ZnO films using either RF magnetron sputtering or electron-beam evaporation. The field-effect mobility (µ FE ) of the device prepared by the latter method is as high as 40 cm 2 ·V -1 ·s -1 , one order of magnitude higher than those typically observed for polycrystalline channel devices. However, hysteresis appears in transfer characteristics. This unfavorable effect is found to be eliminated by the thermal annealing of the entire devices in air. The much larger hysteresis and lower µ FE are observed for the device with sputtered gate insulators. This is presumably due to dense surface states created by ion or electron bombardment during the sputtering.
A Family of MicroRNAs Present in Plants and Animals (2006)

Although many miRNAs are deeply conserved within each kingdom, none are known to be conserved between plants and animals. We identified Arabidopsis thaliana miR854 and miR855, two microRNAs (miRNAs) with multiple binding sites in the 3' untranslated region (3'UTR) of OLIGOURIDYLATE binding PROTEIN1b (At UBP1b), forming miRNA:mRNA interactions similar to those that cause translational repression/mRNA cleavage in animals. At UBP1b encodes a member of a heterogeneous nuclear RNA binding protein (hnRNP) family. The 3'UTR of At UBP1b is sufficient to repress reporter protein expression in tissues expressing miR854 or miR855 (rosette leaves and flowers, respectively) but not where both miRNAs are absent (cauline leaves). Intergenic regions containing sequences closely resembling miR854 are predicted to fold into stable miRNA precursors in animals, and members of the miR854 family are expressed in Caenorhabditis elegans, Mus musculus, and Homo sapiens, all with imperfect binding sites in the 3'UTR of genes encoding the T cell Intracellular Antigen-Related protein, an hnRNP of the UBP1 family. Potential binding sites for miR854 are absent from UBP1-like genes in fungi lacking the miRNA biogenetic machinery. Our results indicate that plants and animals share miRNAs of the miR854 family, suggesting a common origin of these miRNAs as regulators of basal transcriptional mechanisms.
Copper-Dependent Iron Assimilation Pathway in the Model Photosynthetic EukaryoteChlamydomonas reinhardtii (2002)

The unicellular green alga Chlamydomonas reinhardtii is a valuable model for studying metal metabolism in a photosynthetic background. A search of the Chlamydomonas expressed sequence tag database led to the identification of several components that form a copper-dependent iron assimilation pathway related to the high-affinity iron uptake pathway defined originally for Saccharomyces cerevisiae. They include a multicopper ferroxidase (encoded by Fox1), an iron permease (encoded by Ftr1), a copper chaperone (encoded byAtx1), and a copper-transporting ATPase. A cDNA, Fer1, encoding ferritin for iron storage also was identified. Expression analysis demonstrated that Fox1 and Ftrl were coordinately induced by iron deficiency, as were Atx1 and Fer1, although to lesser extents. In addition, Fox1 abundance was regulated at the posttranscriptional level by copper availability. Each component exhibited sequence relationship with its yeast, mammalian, or plant counterparts to various degrees; Atx1 of C. reinhardtii is also functionally related with respect to copper chaperone and antioxidant activities. Fox1 is most highly related to the mammalian homologues hephaestin and ceruloplasmin; its occurrence and pattern of expression in Chlamydomonas indicate, for the first time, a role for copper in iron assimilation in a photosynthetic species. Nevertheless, growth of C. reinhardtii under copper- and iron-limiting conditions showed that, unlike the situation in yeast and mammals, where copper deficiency results in a secondary iron deficiency, copper-deficient Chlamydomonas cells do not exhibit symptoms of iron deficiency. We propose the existence of a copper-independent iron assimilation pathway in this organism.
Magnetic Resonance Imaging of Activated Proliferating Rhesus Macaque T Cells Labeled With Superparamagnetic Monocrystalline Iron Oxide Nanoparticles (2003)

Imaging of adoptively transferred cells in vivo by magnetic resonance imaging (MRI) could provide important information on disease-related patterns of lymphocyte homing in nonhuman primate models of AIDS. As a preliminary study to assess the feasibility of visualizing activated rhesus T cells by MRI, anti-CD3/CD28-expanded CD4+ T lymphocytes were labeled in vitro with monocrystalline iron oxide nanoparticles (MION). Intracellular incorporation of MION was determined by transmission electron microscopy (TEM) and inductively coupled plasma mass spectrography (ICP-MS). Pretreatment with colchicine did not affect MION labeling, suggesting that cellular uptake of MION occurred by adsorptive pinocytosis or receptor-mediated endocytosis. TEM analysis revealed that MION were intracellularly compartmentalized exclusively in the cytoplasm and did not cause any measurable physiologic effects on T-cell function, including viability, proliferation, synthesis of select cytokines (interleukin [IL]-2, IL-4, IL-6, IL-10, tumor necrosis factor-alpha, and interferon-gamma), activation antigens (CD25 and CD69), adhesion molecules (alpha4beta7 and CD49d), and susceptibility to in vitro infection with simian immunodeficiency virus mac239. A sensitivity of 0.05% (1 MION-labeled T cell in 2000 unlabeled cells) could be achieved using T2-weighted gradient echo imaging. Furthermore, under these experimental conditions, the MRI signal did not decrease in proliferating MION-labeled CD4+ T cells over a period of 120 hours. These results indicate that intracellular labeling with MION can be a useful technique for noninvasively monitoring trafficking patterns of adoptively transferred leukocyte subsets in real-time by MRI in nonhuman primate models of AIDS.
Emulsion PCR: A High Efficient Way of PCR Amplification of Random DNA Libraries in Aptamer Selection (2011)

Aptamers are short RNA or DNA oligonucleotides which can bind with different targets. Typically, they are selected from a large number of random DNA sequence libraries. The main strategy to obtain aptamers is systematic evolution of ligands by exponential enrichment (SELEX). Low efficiency is one of the limitations for conventional PCR amplification of random DNA sequence library in aptamer selection because of relative low products and high by-products formation efficiency. Here, we developed emulsion PCR for aptamer selection. With this method, the by-products formation decreased tremendously to an undetectable level, while the products formation increased significantly. Our results indicated that by-products in conventional PCR amplification were from primer-product and product-product hybridization. In emulsion PCR, we can completely avoid the product-product hybridization and avoid the most of primer-product hybridization if the conditions were optimized. In addition, it also showed that the molecule ratio of template to compartment was crucial to by-product formation efficiency in emulsion PCR amplification. Furthermore, the concentration of the Taq DNA polymerase in the emulsion PCR mixture had a significant impact on product formation efficiency. So, the results of our study indicated that emulsion PCR could improve the efficiency of SELEX.
Effect of Gasoline Composition on Emissions of Aromatic Hydrocarbons (1989)

&lt;div class="htmlview paragraph"&gt;The primary objective of this study was to determine the effect of aromatic compounds in gasoline on exhaust emissions of benzene. Previously reported studies have shown that benzene emissions correlate well with fuel content of benzene and total aromatics. The intent was to determine the relative significance of the individual aromatic species as benzene precursors.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;Although benzene combustion exhaust emissions were of primary interest, emissions of other aromatic species were also measured. The experimental design enabled determination of fuel composition effects on emissions of benzene as well as other aromatics.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;A matrix of 16 fuels was formulated with systematic variation in their content of benzene, toluene, ethyl benzene, xylenes, and C&lt;sup&gt;+&lt;/sup&gt;&lt;sub&gt;9&lt;/sub&gt; aromatics. The emission levels of these species were determined in both engine-out and tailpipe-out exhaust from four 1985/86 model year vehicles. The EPA Federal Test Procedure (FTP) was used in all four experiments.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;Results show that the exhaust emission rate of each aromatic component is highly correlated with the level of that component in the fuel and, to a lesser degree, with the content of the other aromatics in the fuel. Comparison of tailpipe-out emissions with engine-out emissions indicates that there were no marked differences in catalyst efficiency for the aromatic compounds included in this study.&lt;/div&gt;
Construction of Stable BHK-21 Cells Coexpressing Human Secretory Glycoproteins and Human Gal(beta1-4)GlcNAc-R alpha2,6-Sialyltransferase. alpha2,6-Linked NeuAc is Preferentially Attached to the Gal(beta1-4)GlcNAc(beta1-2)Man(alpha1-3)-Branch of Diantennary Oligosaccharides from Secreted Recombinant beta-Trace Protein (1995)

The human β-trace protein has been cloned and has been expressed for the first time in a mammalian host cell line. Stable BHK-21 cell lines exhibiting altered terminal sialylation properties were constructed by cotransfection of cells with the plasmids pMT-βTP or pAB3-1 which contain the cDNAs encoding the human secretory glycoproteins β-trace protein or antithrombin III and pABSial containing the human Golgi enzyme CMP-NeuAc:Gal(β1-4)GlcNAc-R α2,6-sialyltransferase (ST6N) gene. The β-trace protein was purified by immunoaffinity chromatography and N-linked oligosaccharides were subjected to carbohydrate structural analysis. The enzymically liberated oligosaccharides were found to consist of 90% of diantennary chains as is the case for natural β-trace protein from human cerebrospinal fluid. About 90% of the total oligosaccharides were recovered in the monosialo and disialo fractions in a ratio of 1:5. The monosialylated oligosaccharides of β-trace protein coexpressed with human ST6N were found to contain NeuAc in α2,6-or α2,3-linkage in the same ratio. From 1H-NMR analysis as well as calculations of peak areas obtained by HPLC, 60% of the molecules of the disialo fraction were found to contain NeuAc in both α2,3-and α2,6-linkage to Galβ(1-4)GlcNAc-R, whereas 40% of the molecules of this fraction contained NeuAc in only α2,3-linkage to Gal(β1-4)GlcNAc-R. The α2,6-linked NeuAc was shown to be attached preferentially to the Gal(β1-4)GlcNAc(β1-2)Man(α1-3) branch of the diantennary structure. Therefore the in vivo specificity of the newly introduced recombinant human ST6N observed in this study supports the previously reported in vitro branch specificity of the bovine colostrum ST6N activity. Furthermore, these studies demonstrate the suitability of genetically engineered mammalian host cell lines with novel glycosylation properties for the production of human-type glycosylated secretory recombinant polypeptides.