gebhart/patrepeval huggingface dataset:
Hyperphosphorylation of Microtubule-Associated Protein Tau: A Promising Therapeutic Target for Alzheimer Disease (2008)

Alzheimer disease (AD) is the most common cause of dementia in adults. The current therapy for AD has only moderate efficacy in controlling symptoms, and it does not cure the disease. Recent studies have suggested that abnormal hyperphosphorylation of tau in the brain plays a vital role in the molecular pathogenesis of AD and in neurodegeneration. This article reviews the current advances in understanding of tau protein, regulation of tau phosphorylation, and the role of its abnormal hyperphosphorylation in neurofibrillary degeneration. Furthermore, several therapeutic strategies for treating AD on the basis of the important role of tau hyperphosphorylation in the pathogenesis of the disease are described. These strategies include (1) inhibition of glycogen synthase kinase-3beta (GSK-3beta), cyclin-dependent kinase 5 (cdk5), and other tau kinases; (2) restoration of PP2A activity; and (3) targeting tau O-GlcNAcylation. Development of drugs on the basis of these strategies is likely to lead to disease-modifying therapies for AD.
Response of Wegener's granulomatosis to anti-CD20 chimeric monoclonal antibody therapy (2001)

We report on the successful, compassionate use of the anti-CD20 chimeric monoclonal antibody rituximab in a patient with chronic, relapsing cytoplasmic antineutrophil cytoplasmic antibody (cANCA)-associated Wegener's granulomatosis (WG). The patient initially responded to treatment with glucocorticoids and cyclophosphamide. However, bone marrow toxicity during cyclophosphamide treatment of a relapse precluded its further use. Azathioprine and mycophenolate mofetil treatment had failed to maintain remission of the WG, and methotrexate was contraindicated. Because the patient's 5-year course was characterized by close correlation of cANCA levels with disease activity, selective elimination of cANCA was deemed a treatment option for his latest relapse. He was given 4 infusions of 375 mg/M2 of rituximab and high-dose glucocorticoids. Complete remission was associated with the disappearance of B lymphocytes and cANCA. Glucocorticoid treatment was then discontinued. After 11 months, the cANCA recurred, and rituximab therapy was repeated, without glucocorticoids. At 8 months after the second course of rituximab (18 months after the first course), the patient's WG has remained in complete remission. Elimination of B cells by rituximab therapy may prove to be an effective and safe new treatment modality for ANCA-associated vasculitis and possibly other autoimmune diseases. This modality warrants closer examination in a carefully conducted clinical trial.
Repetitive increases in cytosolic Ca2+ of guard cells by abscisic acid activation of nonselective Ca2+ permeable channels. (1990)

Many signal-transduction processes in higher plant cells have been suggested to be triggered by signal-induced opening of Ca2+ channels in the plasma membrane. However, direct evidence for activation of plasma-membrane Ca2+ channels by physiological signals in higher plants has not yet been obtained. In this context, several lines of evidence suggest that Ca2+ flux into the cytosol of guard cells is a major factor in the induction of stomatal closing by abscisic acid (ABA). ABA closes stomatal pores, thereby reducing transpirational loss of water by plants under drought conditions. To directly investigate initial events in ABA-induced signal transduction in guard cells, we devised an experimental approach that allows simultaneous photometric measurements of cytosolic Ca2+ and patch-clamp recordings of ion currents across the plasma membrane of single Vicia faba guard cells. Using this approach, we found that the resting cytosolic Ca2+ concentration was 0.19 +/- 0.09 microM (n = 19). In responsive guard cells, external exposure to ABA produced transient repetitive increases in the cytosolic free Ca2+ concentration. These Ca2+ transients were accompanied by concomitantly occurring increases in an inward-directed ion current. Depolarization of the membrane terminated both repetitive elevations in cytosolic Ca2+ and inward-directed ion currents, suggesting that ABA-mediated Ca2+ transients were produced by passive influx of Ca2+ from the extracellular space through Ca2(+)-permeable channels. Detailed voltage-clamp measurements revealed that ABA-activated ion currents could be reversed by depolarizations more positive than -10 mV. Interestingly, reversal potentials of ABA-induced currents show that these currents are not highly Ca2(+)-selective, thereby permitting permeation of both Ca2+ and K+. These results provide direct evidence for ABA activation of Ca2(+)-permeable ion channels in the plasma membrane of guard cells. ABA-activated ion channels allow repetitive elevations in the cytosolic Ca2+ concentration, which, in turn, can modulate cellular responses promoting stomatal closure.
Study on properties of ABS with damp & heat aging (2000)

The property of ABS sheet and cooling tower parts with damp heat aging has been studied. It is showed that the properties are not changed in normal temperature water. The change of property is accelerated with raising temperature. A series of aging phenomenon of which color of ABS sheet changes to dark and the properties go bad has taken place. Macromolecule is broken more easily. Polar group and low molecule has been produced. The tensile strength and impact strength is continuously fallen with L curve. Macromolecular cross-link has been formed much more during the middle and later period of damp heat air aging. The change of property is slowed down and the strength has gone up again. ABS plastics are belong to the one of which humidity can accelerate the aging. It is suggested that the tensile strength and impact strength of wet ABS sample through hot water aging may be used to judge its damp heat aging properties. The test condition and qualified target has been determined and be used in related specialized standard.
Electric Manipulation of Bioparticles and Macromolecules on Microfabricated Electrodes (2001)

Bioparticle separation, bioparticle enrichment, and electric field-mediated immune detection were carried out on microfabricated semiconductor chips utilizing ac and dc electric fields. Microscale separation on a chip surface having an active area of approximately 16 mm2 was demonstrated for a mixture of Bacillus globigii spores and Escherichia coli bacteria. Dielectrophoretic enrichment was performed by collecting target bioparticles from a flow stream in flow cells of 47.5 microL, achieving a 20-fold increase in the concentration of E. coli bacteria from a diluted sample, a 28-fold enrichment for peripheral blood mononuclear cells from red blood cells, and a 30-fold increase in white blood cells from diluted whole blood. The ability to manipulate and collect bioparticles and macromolecules at microfabricated electrodes with ac and dc fields was further illustrated in electric field-mediated immunoassays for analyzing the biological identities of E. coli bacteria and B. globigii spores. According to these results, the electric methods for manipulating bioparticles present themselves as viable techniques for novel biomedical applications in sample preparations and biochemical assays on microelectrode arrays.
Correction of geometric and refractive image distortions in optical coherence tomography applying Fermat�??s principle (2002)

We describe a methodology for quantitative image correction in OCT which includes procedures for correction of nonlinear axial scanning and non-telecentric scan patterns, as well as a novel approach for refraction correction in layered media based on Fermat's principle. The residual spatial error obtained in layered media with a fan-beam hand-held probe was reduced from several hundred micrometers to near the diffraction and coherence-length limits.
Design and Synthesis of β-Site Amyloid Precursor Protein Cleaving Enzyme (BACE1) Inhibitors with in Vivo Brain Reduction of β-Amyloid Peptides (2012)

The evaluation of a series of aminoisoindoles as β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors and the discovery of a clinical candidate drug for Alzheimer's disease, (S)-32 (AZD3839), are described. The improvement in permeability properties by the introduction of fluorine adjacent to the amidine moiety, resulting in in vivo brain reduction of Aβ40, is discussed. Due to the basic nature of these compounds, they displayed affinity for the human ether-a-go-go related gene (hERG) ion channel. Different ways to reduce hERG inhibition and increase hERG margins for this series are described, culminating in (S)-16 and (R)-41 showing large in vitro margins with BACE1 cell IC(50) values of 8.6 and 0.16 nM, respectively, and hERG IC(50) values of 16 and 2.8 μM, respectively. Several compounds were advanced into pharmacodynamic studies and demonstrated significant reduction of β-amyloid peptides in mouse brain following oral dosing.
Vaccines '97 : Molecular approaches to the control of infectious diseases (1997)

Immunogenic structures interaction of antigens with the immune system cytokines, pathogenesis and vaccines emerging pathogens DNA immunization bacterial vaccines parasite vaccines viral vaccines HIV-SIV the Albert B. Sabin Lecture.
A data locality optimizing algorithm (1991)

article Free Access Share on A data locality optimizing algorithm Authors: Michael E. Wolf Computer Systems Laboratory, Stanford University, CA Computer Systems Laboratory, Stanford University, CAView Profile , Monica S. Lam Computer Systems Laboratory, Stanford University, CA Computer Systems Laboratory, Stanford University, CAView Profile Authors Info & Claims ACM SIGPLAN NoticesVolume 26Issue 6June 1991 pp 30–44https://doi.org/10.1145/113446.113449Online:01 May 1991Publication History 1,081citation3,261DownloadsMetricsTotal Citations1,081Total Downloads3,261Last 12 Months187Last 6 weeks25 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Novel DNA probes with low background and high hybridization-triggered fluorescence (2007)

Novel fluorogenic DNA probes are described. The probes (called Pleiades) have a minor groove binder (MGB) and a fluorophore at the 5'-end and a non-fluorescent quencher at the 3'-end of the DNA sequence. This configuration provides surprisingly low background and high hybridization-triggered fluorescence. Here, we comparatively study the performance of such probes, MGB-Eclipse probes, and molecular beacons. Unlike the other two probe formats, the Pleiades probes have low, temperature-independent background fluorescence and excellent signal-to-background ratios. The probes possess good mismatch discrimination ability and high rates of hybridization. Based on the analysis of fluorescence and absorption spectra we propose a mechanism of action for the Pleiades probes. First, hydrophobic interactions between the quencher and the MGB bring the ends of the probe and, therefore, the fluorophore and the quencher in close proximity. Second, the MGB interacts with the fluorophore and independent of the quencher is able to provide a modest (2-4-fold) quenching effect. Joint action of the MGB and the quencher is the basis for the unique quenching mechanism. The fluorescence is efficiently restored upon binding of the probe to target sequence due to a disruption in the MGB-quencher interaction and concealment of the MGB moiety inside the minor groove.
Structural Mechanisms Underlying Posttranslational Modification by Ubiquitin-Like Proteins (2007)

Covalent attachment of ubiquitin-like proteins (Ubls) is a predominant mechanism for regulating protein function in eukaryotes. Several structurally related Ubls, such as ubiquitin, SUMO, NEDD8, and ISG15, modify a vast number of proteins, altering their functions in a variety of ways. Ubl modifications can affect the target's half-life, subcellular localization, enzymatic activity, or ability to interact with protein or DNA partners. Generally, these diverse Ubls are covalently attached via their C termini to their targets by parallel, but specific, cascades involving three classes of enzymes known as E1, E2, and E3. Structures are now available for many protein complexes in E1-E2-E3 cascades, revealing a series of modular building blocks and providing mechanistic insights into their functions.
Mussel-Inspired Surface Chemistry for Multifunctional Coatings (2007)

We report a method to form multifunctional polymer coatings through simple dip-coating of objects in an aqueous solution of dopamine. Inspired by the composition of adhesive proteins in mussels, we used dopamine self-polymerization to form thin, surface-adherent polydopamine films onto a wide range of inorganic and organic materials, including noble metals, oxides, polymers, semiconductors, and ceramics. Secondary reactions can be used to create a variety of ad-layers, including self-assembled monolayers through deposition of long-chain molecular building blocks, metal films by electroless metallization, and bioinert and bioactive surfaces via grafting of macromolecules.
The CXC Chemokine Receptor 2, CXCR2, Is the Putative Receptor for ELR+ CXC Chemokine-Induced Angiogenic Activity (2000)

We have previously shown that members of the ELR(+) CXC chemokine family, including IL-8; growth-related oncogenes alpha, beta, and gamma; granulocyte chemotactic protein 2; and epithelial neutrophil-activating protein-78, can mediate angiogenesis in the absence of preceding inflammation. To date, the receptor on endothelial cells responsible for chemotaxis and neovascularization mediated by these ELR(+) CXC chemokines has not been determined. Because all ELR(+) CXC chemokines bind to CXC chemokine receptor 2 (CXCR2), we hypothesized that CXCR2 is the putative receptor for ELR(+) CXC chemokine-mediated angiogenesis. To test this postulate, we first determined whether cultured human microvascular endothelial cells expressed CXCR2. CXCR2 was detected in human microvascular endothelial cells at the protein level by both Western blot analysis and immunohistochemistry using polyclonal Abs specific for human CXCR2. To determine whether CXCR2 played a functional role in angiogenesis, we determined whether this receptor was involved in endothelial cell chemotaxis. We found that microvascular endothelial cell chemotaxis in response to ELR(+) CXC chemokines was inhibited by anti-CXCR2 Abs. In addition, endothelial cell chemotaxis in response to ELR(+) CXC chemokines was sensitive to pertussis toxin, suggesting a role for G protein-linked receptor mechanisms in this biological response. The importance of CXCR2 in mediating ELR(+) CXC chemokine-induced angiogenesis in vivo was also demonstrated by the lack of angiogenic activity induced by ELR(+) CXC chemokines in the presence of neutralizing Abs to CXCR2 in the rat corneal micropocket assay, or in the corneas of CXCR2(-/-) mice. We thus conclude that CXCR2 is the receptor responsible for ELR(+) CXC chemokine-mediated angiogenesis.
Embedding image watermarks in dc components (2000)

Both watermark structure and embedding strategy affect robustness of image watermarks. Where should watermarks be embedded in the discrete cosine transform (DCT) domain in order for the invisible image watermarks to be robust? Though many papers in the literature agree that watermarks should be embedded in perceptually significant components, dc components are explicitly excluded from watermark embedding. In this letter, a new embedding strategy for watermarking is proposed based on a quantitative analysis on the magnitudes of DCT components of host images. We argue that more robustness can be achieved if watermarks are embedded in dc components since dc components have much larger perceptual capacity than any ac components. Based on this idea, an adaptive watermarking algorithm is presented. We incorporate the feature of texture masking and luminance masking of the human visual system into watermarking. Experimental results demonstrate that the invisible watermarks embedded with the proposed watermark algorithm are very robust.
Temporal and selective association of multiple sigma factors with RNA polymerase during sporulation in Bacillus subtilis (2000)

As the core RNA polymerase is in excess, the results suggest that successive sigma factors can bind to core RNA polymerase without having to displace earlier appearing sigma factors. Thus, the programme of gene expression during sporulation might not require mechanisms for the substitution of one sigma factor by another on the core RNA polymerase.
Assembly of Aqueous-Cored Calcium Phosphate Nanoparticles for Drug Delivery (2004)

A synthesis strategy for aqueous-cored calcium phosphate nanoparticles is presented that combines ease of preparation, reproducibility, size control, stability, and mean thickness control. Suspension stability and shell thickness control were achieved through the introduction of a “capping” molecule, carboxyethylphosphoric acid (CEPA). Using this method, suspensions of calcium phosphate shells were produced with a size distribution of 120−185 ± 50 nm and predictable mean shell thickness from 10 to 40 nm that were stable up to a month, even in the presence of 200 mM salt and 2.5 g/dL albumin.
Two Seven-Transmembrane Domain MILDEW RESISTANCE LOCUS O Proteins Cofunction inArabidopsisRoot Thigmomorphogenesis (2009)

Directional root expansion is governed by nutrient gradients, positive gravitropism and hydrotropism, negative phototropism and thigmotropism, as well as endogenous oscillations in the growth trajectory (circumnutation). Null mutations in phylogenetically related Arabidopsis thaliana genes MILDEW RESISTANCE LOCUS O 4 (MLO4) and MLO11, encoding heptahelical, plasma membrane-localized proteins predominantly expressed in the root tip, result in aberrant root thigmomorphogenesis. mlo4 and mlo11 mutant plants show anisotropic, chiral root expansion manifesting as tightly curled root patterns upon contact with solid surfaces. The defect in mlo4 and mlo11 mutants is nonadditive and dependent on light and nutrients. Genetic epistasis experiments demonstrate that the mutant phenotype is independently modulated by the Gbeta subunit of the heterotrimeric G-protein complex. Analysis of expressed chimeric MLO4/MLO2 proteins revealed that the C-terminal domain of MLO4 is necessary but not sufficient for MLO4 action in root thigmomorphogenesis. The expression of the auxin efflux carrier fusion, PIN1-green fluorescent protein, the pattern of auxin-induced gene expression, and acropetal as well as basipetal auxin transport are altered at the root tip of mlo4 mutant seedlings. Moreover, addition of auxin transport inhibitors or the loss of EIR1/AGR1/PIN2 function abolishes root curling of mlo4, mlo11, and wild-type seedlings. These results demonstrate that the exaggerated root curling phenotypes of the mlo4 and mlo11 mutants depend on auxin gradients and suggest that MLO4 and MLO11 cofunction as modulators of touch-induced root tropism.
Expression of human ARD1 in squamous epithelium,squamous cell carcinoma (2010)

Objective To investigate the expression and possible role of human arrest defective 1(hARD1) in squamous epithelium and squamous cell carcinoma(SCC).Methods Firstly,polyclonal anti-hARD1 antibody was prepared and characterized. Then,the expression of hARD1 in various differentiated SCC and squamous epithelium(control tissues) which were from skins, lungs,oesophaguses and cervices was detected by immunohistochemical method and was compared with each other.Results Compared with control tissues,the expression of hARD1 was significantly down-regulated in squamous cell carcinoma,especially in poor differentiated carcinoma(P0.001) and was positively associated with the differentiation of squamous cell(r=0.493,P0.001). Conclusion The expression of hARD1 was positively associated with the differentiation of squamous cell.Namely,Poorer differentiation tended to show lower hARD1 expression.
Fluorescein angiography as a means of assessing retinal vascular pathology in oxygen-exposed newborn rats (1993)

Recently a new technique was reported in which examination of the retina of oxygen reared newborn rats was made using indirect fluorescence microscopy (Invest. Ophthal. Vis. Sci. 31:810). We have now improved this technique and systematically employed it as a means of studying oxygen-induced retinopathy in the newborn rat as an animal model for retinopathy of prematurity (ROP). Immediately after birth, litters of pigmented rats were exposed to an elevated oxygen atmosphere that varied in a cyclic fashion between 40% and 80% every 12 hours for 14 days. Rats raised simultaneously in room air served as controls. At the end of the treatment period, rats were deeply anesthetized, their pupils dilated, and 100 microliters of 3% sodium fluorescein was administered via tail venipuncture. After angiography, rats were awakened and returned to their mothers in room air for future assessment. Angiography was performed again at 4, 7, 38 or 56 days after oxygen treatment. Our results suggest that retinal pathology in the rat model parallels that of the human infant with ROP with respect to loss of patent retinal blood vessels in oxygen and subsequent abnormal vasoproliferation upon return to room air. Angiograms performed on room air-raised control rats at 14 days of age demonstrated our ability to resolve the smallest retinal capillaries. Angiograms conducted at the same age in oxygen-exposed rats revealed extensive areas of retinal non-perfusion and substantial arterio-venous shunting between adjacent primary vessels. If rats were maintained in room air for 4 or 7 days following oxygen exposure, a variety of pathologic signs became obvious including: 1) tortuosity of primary vessels mimicking human "plus disease", 2) frequent abnormal budding of tertiary vessels and capillaries, 3) retinal fluorescein leaks indicative of hemorrhages and 4) abnormal capillary tufts not evident at the time of removal from oxygen. By 38 and 56 days post-exposure, all four of these phenomena were still observed. Many of these pathologic phenomena could not have been observed with conventional methods currently used for retinal vascular assessment in small animals.