gebhart/patrepeval huggingface dataset:
Decorin-binding Sites for Collagen Type I Are Mainly Located in Leucine-rich Repeats 4-5 (1995)

Decorin and biglycan are structurally related interstitial proteoglycans synthesized in connective tissues like skin, tendon, and cartilage. Despite the conspicuous sequence similarities, where about 55% of the amino acid residues in decorin and biglycan are located in identical positions, the two proteoglycans show differences in their interaction with collagen. Decorin binds to collagen type I, whereas biglycan in several assay systems shows no affinity for this collagen type. Here we have made use of these structural similarities and affinity differences in studies of the collagen binding properties of decorin. Recombinant biglycan/decorin chimeras were produced in mammalian cells and analyzed for their capacity to bind collagen. In the chimeras, biglycan contributes sequences crucial for synthesis and export from the mammalian cells, and decorin provides potential collagen-binding properties. By using this approach we show that decorin binds to the collagen primarily via leucine-rich repeats 4-5 composed of some 40 amino acid residues. Proteoglycan chimeras containing decorin sequences from the N terminus to leucine-rich repeat 3 or sequences from leucine-rich repeat 6 to the C terminus do not show any detectable binding to collagen. A proteoglycan chimera containing decorin leucine-rich repeats 4-5 flanked by biglycan sequences binds to collagen. However, this chimera binds to collagen with somewhat lower affinity than wild type decorin, suggesting that additional low affinity binding sites may be located in other parts of decorin. Alternatively, the conformation of the collagen binding leucine-rich repeats 4-5 are different in decorin and in the biglycan/decorin chimera, leading to a lower collagen affinity for the latter.
An oligosaccharide-based HIV-1 2G12 mimotope vaccine induces carbohydrate-specific antibodies that fail to neutralize HIV-1 virions (2008)

The conserved oligomannose epitope, Man(9)GlcNAc(2), recognized by the broadly neutralizing human mAb 2G12 is an attractive prophylactic vaccine candidate for the prevention of HIV-1 infection. We recently reported total chemical synthesis of a series of glycopeptides incorporating one to three copies of Man(9)GlcNAc(2) coupled to a cyclic peptide scaffold. Surface plasmon resonance studies showed that divalent and trivalent, but not monovalent, compounds were capable of binding 2G12. To test the efficacy of the divalent glycopeptide as an immunogen capable of inducing a 2G12-like neutralizing antibody response, we covalently coupled the molecule to a powerful immune-stimulating protein carrier and evaluated immunogenicity of the conjugate in two animal species. We used a differential immunoassay to demonstrate induction of high levels of carbohydrate-specific antibodies; however, these antibodies showed poor recognition of recombinant gp160 and failed to neutralize a panel of viral isolates in entry-based neutralization assays. To ascertain whether antibodies produced during natural infection could recognize the mimetics, we screened a panel of HIV-1-positive and -negative sera for binding to gp120 and the synthetic antigens. We present evidence from both direct and competitive binding assays that no significant recognition of the glycopeptides was observed, although certain sera did contain antibodies that could compete with 2G12 for binding to recombinant gp120.
Trehalose, a Novel mTOR-independent Autophagy Enhancer, Accelerates the Clearance of Mutant Huntingtin and α-Synuclein (2006)

Trehalose, a disaccharide present in many non-mammalian species, protects cells against various environmental stresses. Whereas some of the protective effects may be explained by its chemical chaperone properties, its actions are largely unknown. Here we report a novel function of trehalose as an mTOR-independent autophagy activator. Trehalose-induced autophagy enhanced the clearance of autophagy substrates like mutant huntingtin and the A30P and A53T mutants of alpha-synuclein, associated with Huntington disease (HD) and Parkinson disease (PD), respectively. Furthermore, trehalose and mTOR inhibition by rapamycin together exerted an additive effect on the clearance of these aggregate-prone proteins because of increased autophagic activity. By inducing autophagy, we showed that trehalose also protects cells against subsequent pro-apoptotic insults via the mitochondrial pathway. The dual protective properties of trehalose (as an inducer of autophagy and chemical chaperone) and the combinatorial strategy with rapamycin may be relevant to the treatment of HD and related diseases, where the mutant proteins are autophagy substrates.
Antisense Inhibition of Threonine Synthase Leads to High Methionine Content in Transgenic Potato Plants (2001)

Methionine (Met) and threonine (Thr) are members of the aspartate family of amino acids. In plants, their biosynthetic pathways diverge at the level of O-phosphohomo-serine (Ser). The enzymes cystathionine gamma-synthase and Thr synthase (TS) compete for the common substrate O-phosphohomo-Ser with the notable feature that plant TS is activated through S-adenosyl-Met, a metabolite derived from Met. To investigate the regulation of this branch point, we engineered TS antisense potato (Solanum tuberosum cv Désirée) plants using the constitutive cauliflower mosaic virus 35S promoter. In leaf tissues, these transgenics exhibit a reduction of TS activity down to 6% of wild-type levels. Thr levels are reduced to 45% wild-type controls, whereas Met levels increase up to 239-fold depending on the transgenic line and environmental conditions. Increased levels of homo-Ser and homo-cysteine indicate increased carbon allocation into the aspartate pathway. In contrast to findings in Arabidopsis, increased Met content has no detectable effect on mRNA or protein levels or on the enzymatic activity of cystathionine gamma-synthase in potato. Tubers of TS antisense potato plants contain a Met level increased by a factor of 30 and no reduction in Thr. These plants offer a major biotechnological advance toward the development of crop plants with improved nutritional quality.
Translation of DNA into a Library of 13 000 Synthetic Small-Molecule Macrocycles Suitable for in Vitro Selection (2008)

DNA-templated organic synthesis enables the translation, selection, and amplification of DNA sequences encoding synthetic small-molecule libraries. Previously we described the DNA-templated multistep synthesis and model in vitro selection of a pilot library of 65 macrocycles. In this work, we report several key developments that enable the DNA-templated synthesis of much larger (>10,000-membered) small-molecule libraries. We developed and validated a capping-based approach to DNA-templated library synthesis that increases final product yields, simplifies the structure and preparation of reagents, and reduces the number of required manipulations. To expand the size and structural diversity of the macrocycle library, we augmented the number of building blocks in each DNA-templated step from 4 to 12, selected 8 different starting scaffolds which result in 4 macrocycle ring sizes and 2 building-block orientations, and confirmed the ability of the 36 building blocks and 8 scaffolds to generate DNA-templated macrocycle products. We computationally generated and experimentally validated an expanded set of codons sufficient to support 1728 combinations of step 1, step 2, and step 3 building blocks. Finally, we developed new high-resolution LC/MS analysis methods to assess the quality of large DNA-templated small-molecule libraries. Integrating these four developments, we executed the translation of 13,824 DNA templates into their corresponding small-molecule macrocycles. Analysis of the resulting libraries is consistent with excellent (>90%) representation of desired macrocycle products and a stringent test of sequence specificity suggests a high degree of sequence fidelity during translation. The quality and structural diversity of this expanded DNA-templated library provides a rich starting point for the discovery of functional synthetic small-molecule macrocycles.
High mobility group (HMG) non-histone chromosomal proteins HMG1 and HMG2 are significant target antigens of perinuclear anti-neutrophil cytoplasmic antibodies in autoimmune hepatitis (1999)

HMG1 and HMG2 are significant target antigens of p-ANCA in AIH.
Static methods in hybrid branch prediction (1998)

Hybrid branch predictors combine the predictions of multiple single-level or two-level branch predictors. The prediction-combining hardware-the meta-predictor-may itself be large, complex and slow. We show that the combination function is better performed statically, using prediction hints in the branch instructions. The hints are set by profiling or static analysis. Although the meta-predictor is static, the actual predictions remain dynamic, so there is little risk of worst-case performance. An important advantage of our approach is that a branch site only causes interference within a single component predictor reducing capacity demands. We argue that our proposal is implementable, and that it addresses the scaling issues currently facing hardware designers. We show that the static hybrid method we propose is more effective than existing techniques based on dynamic selection, and requires less hardware. For example, one result shows a conventional 4096-bit dynamic selection mechanism getting a 4.7% average miss rate, while our static approach gets 3.6%. These results are obtained with the Instruction Benchmark Suite (IBS), a realistic whole-system benchmark, and the SPECint95 suite, using realistic hardware sizes. All the results we present are based on a cross-validation methodology, in which the profile data used for static selection are based on training inputs that are entirely different from the inputs used to evaluate the performance of the technique.
Imaging Dynamic Redox Changes in Mammalian Cells with Green Fluorescent Protein Indicators (2004)

Changes in the redox equilibrium of cells influence a host of cell functions. Alterations in the redox equilibrium are precipitated by changing either the glutathione/glutathione-disulfide ratio (GSH/GSSG) and/or the reduced/oxidized thioredoxin ratio. Redox-sensitive green fluorescent proteins (GFP) allow real time visualization of the oxidation state of the indicator. Ratios of fluorescence from excitation at 400 and 490 nm indicate the extent of oxidation and thus the redox potential while canceling out the amount of indicator and the absolute optical sensitivity. Because the indicator is genetically encoded, it can be targeted to specific proteins or organelles of interest and expressed in a wide variety of cells and organisms. We evaluated roGFP1 (GFP with mutations C48S, S147C, and Q204C) and roGFP2 (the same plus S65T) with physiologically or toxicologically relevant oxidants both in vitro and in living mammalian cells. Furthermore, we investigated the response of the redox probes under physiological redox changes during superoxide bursts in macrophage cells, hyperoxic and hypoxic conditions, and in responses to H(2)O(2)-stimulating agents, e.g. epidermal growth factor and lysophosphatidic acid.
Cytokine-Induced Injury of the Lacrimal and Salivary Glands (2002)

Damages to the lacrimal and salivary glands that accompany various autoimmune diseases are categorized as secondary Sjögren syndrome. Cytokines and free radicals are thought to be responsible for the pathologic changes, but the precise mechanisms are not clear. We evaluated whether cytokines alone can cause the damages in these exocrine tissues, and whether gaseous molecules such as nitric oxide (NO) play a role in these injuries. Various knockout (KO) mice as well as wild-type mice were injected intraperitoneally (i.p.) with the proinflammatory cytokines, IL-12 and IL-18, singly or in combination. Concurrent administration of IL-12 and IL-18 to mice caused serious atrophy in the lacrimal and salivary glands, which was spared when each cytokine was singly administered. Microscopically, there were apparently no infiltrating cells; nonetheless, numerous apoptotic cells were observed in the epithelium, which was confirmed by DNA ladder formation on gel electrophoresis. Serum levels of IFN-γ and NO2/NO3 were markedly elevated. Combined injections of IL-12 and IL-18 caused the same changes in Fas-deficient and Fas-ligand deficient mice, as well as in perforin-KO mice, but the same changes were not detected in inducible NO synthase-KO mice or IFN-γ KO mice. Thus, the synergistic effect of IL-12 and IL-18 was dependent on production of IFN-γ and NO, but independent of Fas/Fas ligand system and perforin-dependent cytotoxic T cells. IL-18 together with IL-12 caused destructive changes in the glandular tissues without apparent lymphocyte infiltration. It is suggested that these cytokines can mediate apoptosis in glandular epithelial cells and that the elevated NO production is responsible for the change.
Sensing Capabilities of Colloidal Gold Modified with a Self-Assembled Monolayer of a Glucose-Carrying Polymer Chain on a Glass Substrate (2004)

A disulfide-carrying polymer with pendent glucose residues (poly(2-methacryloyloxyethyl d-glucopyranoside)) was obtained by using a benzyl N,N-diethyldithiocarbamoyl derivative which shows the abilities of initiation, chain transfer, and termination (iniferter). The disulfide-carrying polymer was accumulated on a colloidal Au-immobilized glass substrate, and the usefulness of the polymer as a sensing element of concanavalin A (Con A) was examined by using a UV−visible spectrophotometer with the help of surface plasmon resonance. The sensor showed a concentration-dependent specific binding of Con A with a detection limit of 1.9 nM, and furthermore, it had a very high stability at high ionic strength. The polymer-coated device examined here was not only useful as a simple biosensor chip but is also expected to expand our knowledge of interfacial phenomena by introducing various functional polymers on colloidal Au.
Movement Recognition Using Body Area Networks (2009)

Significant research has been done on recognizing the daily activities using acceleration data but few works have focused on classifying the movements comprising an activity due to the shorter time scales of the movements compared to that of an activity. Recognizing the individual movements within an activity can help improve the activity recognition on the whole by using the extra information from the movement granularity. Also, for many applications such as rehabilitation, sports medicine, geriatric care, and health/fitness monitoring the importance of movement recognition cannot be overlooked. Hence, in this paper a novel machine learning algorithm using body area networks is proposed that can on the fly, jointly classify the type of movements, and starting and finishing instant of each movement within an activity. A case study on the best set of features and minimum number of accelerometers needed to correctly classify movements within a smoking activity is also presented.
Die Staudinger‐Ligation – ein Geschenk für die Chemische Biologie (2004)

Abstract Obwohl die Reaktion von Aziden mit Phosphanen zu Aza‐Yliden schon vor mehr als 80 Jahren von Hermann Staudinger entdeckt worden ist und seither in der Organischen Synthese vielfältige Anwendung gefunden hat, wurde ihr Potenzial als eine hoch chemoselektive Ligationsmethode zur Herstellung von Biokonjugaten erst vor kurzem erkannt. Dabei sind die beiden Reaktionspartner zu fast allen in biologischen Systemen präsenten funktionellen Gruppen bioorthogonal und reagieren sogar in wässriger Umgebung bei Raumtemperatur. Dies ermöglicht die Anwendung der Staudinger‐Ligation auch in der komplexen Umgebung einer lebenden Zelle. Dieser Kurzaufsatz schildert den gegenwärtigen Kenntnisstand zu dieser Reaktion und ihrer Anwendung in der Herstellung von Biokonjugaten und als Ligationsmethode in der Chemischen Biologie.
SomaticSniper: identification of somatic point mutations in whole genome sequencing data (2011)

Supplementary data are available at Bioinformatics online.
Improvement of Schwann Cell Attachment and Proliferation on Modified Hyaluronic Acid Strands by Polylysine (2000)

Hyaluronic acid (HyA) has the intrinsic ability to promote cell proliferation and reduce scar formation. However, the clinical use of HyA has so far been limited because of its water solubility and nonadhesive characteristics. Increasing interest in HyA as a clinically useful biomaterial has prompted our study of altering HyA's physical properties to render it a potential component of nerve grafts. In this study, strands of HyA were cross-linked by glutaraldehyde (Glut), coated with polylysine, and then inoculated with Schwann cells (SCs). Results in vivo and in vitro demonstrated that cross-linked HyA strands were water insoluble and thus less biodegradable. Poly-D-lysine-resurfaced strands showed significant SC attachment of 350-400 cells/mm(2), compared to uncoated controls (0-10 cells/mm(2), p < 0.01). Fibroblast control groups showed an attachment of 40-100 cells/mm(2) on coated strands. Immunostaining for proliferating cells showed SCs as and fibroblasts as +. Cells neither adhered to nor proliferated on the modified HyA strands that were not resurfaced. The results suggest that polylysine promotes SC attachment and proliferation to glutaraldehyde-cross-linked HyA strands, the product being a three-dimensional composite with low solubility that may have potential application in nerve grafts.
Effect of Eccentricity, Voids, Cement Channels, and Pore Pressure Decline on Collapse Resistance of Casing (2004)

Abstract Conventional collapse design is based upon uniform external pressure loading. Conventional design considers pore pressure and does not account for the effects on casing stresses from the external cement sheath and surrounding formation. In addition, the conventional design does not predict the collapse load of non-uniform loaded casing that arises from imperfect cement jobs and formation voids. This paper presents the results of a finite element study of casing subjected to external, non-uniform loading. These loads include the effects of cement channels and voids, surrounding formation voids, and pore pressure decline in those voids. A better understanding of these common downhole conditions will help to better understand the resultant stress fields and enable a more accurate determination of the necessary collapse strength of casing.
Evidence that a minor groove-binding peptide and a major groove-binding protein can simultaneously occupy a common site on DNA (1992)

Affinity cleaving proteins have been synthesized based on the DNA-binding domain of the yeast transcriptional activator GCN4 with the DNA cleaving moiety Fe.EDTA attached at the NH2 terminus [Oakley, M. G., & Dervan, P. B. (1990) Science 248, 847]. Cleavage patterns generated by Fe-EDTA-GCN4(226-281) bound to the DNA sites 5'-CTGACTAAT-3' and 5'-ATGACTCTT-3' reveal that the NH2 termini of the GCN4 DNA-binding domain are located in the major groove of DNA, 9-10 base pairs apart, consistent with a Y-shaped dimeric structure. 1-Methylimidazole-2-carboxamide netropsin (2-ImN) is a designed synthetic peptide which binds in the minor groove of DNA at 5'-TGACT-3' sites as an antiparallel, side-by-side dimer [Mrksich, M., Wade, W. S., Dwyer, T. J., Geierstanger, B. H., Wemmer, D.E., & Dervan, P. B. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 7586]. Through the use of Fe.EDTA-GCN4(226-281) as a sequence-specific footprinting agent, it is shown that the dimeric protein GCN4-(226-281) and the dimeric peptide 2-ImN can simultaneously occupy their common binding site in the major and minor grooves of DNA, respectively. The association constants for 2-ImN in the presence and in the absence of Fe.EDTA-GCN4(226-281) are found to be similar, suggesting that the binding of the two dimers is not cooperative.
Recombinant peanut allergen Ara h I expression and IgE binding in patients with peanut hypersensitivity. (1995)

Peanut allergy is a significant health problem because of the frequency, the potential severity, and the chronicity of the allergic sensitivity. Serum IgE from patients with documented peanut hypersensitivity reactions and a peanut cDNA expression library were used to identify clones that encode peanut allergens. One of the major peanut allergens, Ara h I, was selected from these clones using Ara h I specific oligonucleotides and polymerase chain reaction technology. The Ara h I clone identified a 2.3-kb mRNA species on a Northern blot containing peanut poly (A)+ RNA. DNA sequence analysis of the cloned inserts revealed that the Ara h I allergen has significant homology with the vicilin seed storage protein family found in most higher plants. The isolation of the Ara h I clones allowed the synthesis of this protein in E. coli cells and subsequent recognition of this recombinant protein in immunoblot analysis using serum IgE from patients with peanut hypersensitivity. With the production of the recombinant peanut protein it will now be possible to address the pathophysiologic and immunologic mechanisms regarding peanut hypersensitivity reactions specifically and food hypersensitivity in general
Effects of biofilm structures on oxygen distribution and mass transport (1994)

Aerobic biofilms were found to have a complex structure consisting of microbial cell clusters (discrete aggregates of densely packed cells) and interstitial voids. The oxygen distribution was strongly correlated with these strutures. The voids facilitated oxygen transport from the bulk liquid through the biofilm, supplying approximately 50% of the total oxygen consumed by the cells. The mass transport rate from the bulk liquid is influenced by the biofilm structure; the observed exchange surface of the biofilm is twice that calculated for a simple planar geometry. The oxygen diffusion occurred in the direction normal to the cluster surfaces, the horizontal and vertical components of the oxygen gradients were of equal importance. Consequently, for calculations of mass transfer rates a three-dimensional model is necessary. These findings imply that to accurately describe biofilm activity, the relation between the arrangement of structural components and mass transfer must be undrstood. (c) 1994 John Wiley & Sons, Inc.
Reproducible resistance switching in polycrystalline NiO films (2004)

Negative resistance behavior and reproducible resistance switching were found in polycrystalline NiO films deposited by dc magnetron reactive sputtering methods. Oxygen to argon gas ratio during deposition was critical in deciding the detailed switching characteristics of either bi-stable memory switching or mono-stable threshold switching. Both metallic nickel defects and nickel vacancies influenced the negative resistance and the switching characteristics. We obtained a distribution of low resistance values which were dependent on the compliance current of high-to-low resistance switching. At 200°C, the low-resistance state kept its initial resistance value while the high-resistance state reached 85% of its initial resistance value after 5×105s. We suggested that the negative resistance and the switching mechanism could be described by electron conduction related to metallic nickel defect states existing in deep levels and by small-polaron hole hopping conduction.
LINCS: A linear constraint solver for molecular simulations (1997)

In this article, we present a new LINear Constraint Solver (LINCS) for molecular simulations with bond constraints. The algorithm is inherently stable, as the constraints themselves are reset instead of derivatives of the constraints, thereby eliminating drift. Although the derivation of the algorithm is presented in terms of matrices, no matrix matrix multiplications are needed and only the nonzero matrix elements have to be stored, making the method useful for very large molecules. At the same accuracy, the LINCS algorithm is three to four times faster than the SHAKE algorithm. Parallelization of the algorithm is straightforward. © 1997 John Wiley & Sons, Inc. J Comput Chem 18: 1463–1472, 1997