gebhart/patrepeval huggingface dataset:
Interleukin 10 but not interleukin 4 is a natural suppressant of cutaneous inflammatory responses. (1995)

We have examined the role of endogenously produced interleukin (IL) 4 and IL-10 in the regulation of inflammatory and immune reactions in the skin. In these experiments, irritant and contact hypersensitivity (CH) responses were elicited in mice with targeted disruptions of the IL-4 (IL-4T) or IL-10 (IL-10T) gene. Our study showed that IL-4T and wild-type (wt) mice exhibited equivalent responses to the irritant croton oil. In contrast, the response of IL-10T mice challenged with croton oil was abnormally increased. When IL-10T mice were exposed to a higher dose of irritant, irreversible tissue damage occurred. By comparison, any treatment of wt mice with croton oil resulted in far less tissue damage and resolution of inflammation. Neutralizing antibody studies demonstrated that the necrosis that occurred in IL-10T mice was due to the overproduction of tumor necrosis factor. The anti-tumor necrosis factor antibody treatment of IL-10T mice did not significantly reduce the edema or the influx of inflammatory cells, suggesting that these changes were due to the uncontrolled production of other proinflammatory cytokines. T cell-dependent immune responses were also evaluated using the contact sensitizer oxazolone. The response of IL-4T mice did not differ from wt mice. In contrast, IL-10T mice mounted an exaggerated CH response, increased in both magnitude and duration as compared with wt mice. Based on these studies, we have concluded that IL-10, but not IL-4, is a natural suppressant of irritant responses and of CH, and it limits immunopathologic damage in the skin.
Metabolism and possible health effects of aluminum. (1986)

Literature regarding the biochemistry of aluminum and eight similar ions is reviewed. Close and hitherto unknown similarities were found. A hypothetical model is presented for the metabolism, based on documented direct observations of Al3+ and analogies from other ions. Main characteristics are low intestinal absorption, rapid urinary excretion, and slow tissue uptake, mostly in skeleton and reticuloendothelial cells. Intracellular Al3+ is probably first confined in the lysosomes but then slowly accumulates in the cell nucleus and chromatin. Large, long-lived cells, e.g., neurons, may be the most liable to this accumulation. In heterochromatin, Al3+ levels can be found comparable to those used in leather tannage. It is proposed that an accumulation may take place at a subcellular level without any significant increase in the corresponding tissue concentration. The possible effects of this accumulation are discussed. As Al3+ is neurotoxic, the brain metabolism is most interesting. The normal and the lethally toxic brain levels of Al3+ are well documented and differ only by a factor of 3-10. The normal brain uptake of Al3+ is estimated from data on intestinal uptake of Al3+ and brain uptake of radionuclides of similar ions administered intravenously. The uptake is very slow, 1 mg in 36 years, and is consistent with an assumption that Al3+ taken up by the brain cannot be eliminated and is therefore accumulated. The possibility that Al3+ may cause or contribute to some specific diseases, most of them related to aging, is discussed with the proposed metabolic picture in mind.
Interaction of arterial cells. I. Endothelial cells alter cholesterol metabolism in co-cultured smooth muscle cells. (1985)

Results of previous in vivo experiments indicated that the presence of arterial endothelium modifies cholesteryl ester (CE) metabolism and the retention of low density lipoproteins (LDL) in injured arteries. We describe herein the effects of bovine arterial endothelial cells (ENDO) on the CE cycle, fluid phase endocytosis, and cell proliferation in co-cultured bovine arterial smooth muscle cells (SMC). Following several days of cultivation on confluent SMC, ENDO were removed from SMC by treatment of the co-cultures with 1.0% collagenase (type II). Removal of only ENDO from the co-culture dishes was confirmed by immunofluorescent staining for Factor VIII antigen, hemotoxylin-eosin staining, and biochemical analyses. We observed that ENDO grown to 75% confluency on confluent SMC induced: 1) a reduction of CE hydrolysis as a result of decreased lysosomal CE hydrolytic activity in SMC as compared to SMC cultured alone; and 2) an increase in the rate of incorporation of labeled oleate into CE as a result of increased acyl CoA:cholesterol O-acyltransferase activity in SMC as compared to SMC cultured alone. Neither endothelial cell-derived culture media (ECDM) nor fibroblasts modulated CE metabolism in co-cultured SMC. Additional experiments showed that the presence of endothelial cells or ECDM decreased the proliferation of co-cultured SMC by 50%, but enhanced the endocytotic rate of labeled sucrose into SMC threefold. Results of experiments described herein demonstrate that, in addition to providing a thrombo-resistant surface and regulating permeability, endothelial cells may also serve to modulate cholesteryl ester metabolism in smooth muscle cells derived from the arterial wall.
OMG: Open Molecule Generator (2012)

Computer Assisted Structure Elucidation has been used for decades to discover the chemical structure of unknown compounds. In this work we introduce the first open source structure generator, Open Molecule Generator (OMG), which for a given elemental composition produces all non-isomorphic chemical structures that match that elemental composition. Furthermore, this structure generator can accept as additional input one or multiple non-overlapping prescribed substructures to drastically reduce the number of possible chemical structures. Being open source allows for customization and future extension of its functionality. OMG relies on a modified version of the Canonical Augmentation Path, which grows intermediate chemical structures by adding bonds and checks that at each step only unique molecules are produced. In order to benchmark the tool, we generated chemical structures for the elemental formulas and substructures of different metabolites and compared the results with a commercially available structure generator. The results obtained, i.e. the number of molecules generated, were identical for elemental compositions having only C, O and H. For elemental compositions containing C, O, H, N, P and S, OMG produces all the chemically valid molecules while the other generator produces more, yet chemically impossible, molecules. The chemical completeness of the OMG results comes at the expense of being slower than the commercial generator. In addition to being open source, OMG clearly showed the added value of constraining the solution space by using multiple prescribed substructures as input. We expect this structure generator to be useful in many fields, but to be especially of great importance for metabolomics, where identifying unknown metabolites is still a major bottleneck.
High-affinity single-domain binding proteins with a binary-code interface (2007)

High degrees of sequence and conformation complexity found in natural protein interaction interfaces are generally considered essential for achieving tight and specific interactions. However, it has been demonstrated that specific antibodies can be built by using an interface with a binary code consisting of only Tyr and Ser. This surprising result might be attributed to yet undefined properties of the antibody scaffold that uniquely enhance its capacity for target binding. In this work we tested the generality of the binary-code interface by engineering binding proteins based on a single-domain scaffold. We show that Tyr/Ser binary-code interfaces consisting of only 15-20 positions within a fibronectin type III domain (FN3; 95 residues) are capable of producing specific binding proteins (termed "monobodies") with a low-nanomolar K(d). A 2.35-A x-ray crystal structure of a monobody in complex with its target, maltose-binding protein, and mutation analysis revealed dominant contributions of Tyr residues to binding as well as striking molecular mimicry of a maltose-binding protein substrate, beta-cyclodextrin, by the Tyr/Ser binary interface. This work suggests that an interaction interface with low chemical diversity but with significant conformational diversity is generally sufficient for tight and specific molecular recognition, providing fundamental insights into factors governing protein-protein interactions.
SoftBridge: an architecture for building IP-based bridges over the digital divide (2002)

Abstract — Users and computing equipment have varying capabilities that include the abilities to exchange text and audio, engage in high bandwidth communication, etc. As the technological options increase, effective communication between the different media has be able to bridge across these options: the bridges have to take into account network quality, end-user equipment capabilities as well as user preferences and capabilities. Our research proposes a Soft-Bridge, an abstracted communications platform for the construction of applications across disparate capabilities found in various Digital Divides. We outline the architecture and the requirements that the SoftBridge has to fulfill. An approach and some initial work is described. I.
Quaternions and Rotation Sequences (1999)

Ever since the Irish mathematician William Rowan Hamilton introduced quaternions in the nineteenth century--a feat he celebrated by carving the founding equations into a stone bridge--mathematicians and engineers have been fascinated by these mathematical objects. Today, they are used in applications as various as describing the geometry of spacetime, guiding the Space Shuttle, and developing computer applications in virtual reality. In this book, J. B. Kuipers introduces quaternions for scientists and engineers who have not encountered them before and shows how they can be used in a variety of practical situations. The book is primarily an exposition of the quaternion, a 4-tuple, and its primary application in a rotation operator. But Kuipers also presents the more conventional and familiar 3 x 3 (9-element) matrix rotation operator. These parallel presentations allow the reader to judge which approaches are preferable for specific applications. The volume is divided into three main parts. The opening chapters present introductory material and establish the book's terminology and notation. The next part presents the mathematical properties of quaternions, including quaternion algebra and geometry. It includes more advanced special topics in spherical trigonometry, along with an introduction to quaternion calculus and perturbation theory, required in many situations involving dynamics and kinematics. In the final section, Kuipers discusses state-of-the-art applications. He presents a six degree-of-freedom electromagnetic position and orientation transducer and concludes by discussing the computer graphics necessary for the development of applications in virtual reality
α7 Nicotinic Acetylcholine Receptors Mediate β-Amyloid Peptide-induced Tau Protein Phosphorylation (2003)

The Alzheimer's disease pathogenic peptide, beta-amyloid42 (A beta 42), induces tau protein phosphorylation. Because hyperphosphorylated tau is a consistent component of neurofibrillary tangles, a pathological hallmark of Alzheimer's disease, we investigated the signaling molecules involved in A beta 42-induced tau phosphorylation. We show that A beta 42 elicited rapid and reversible tau protein phosphorylation on three proline-directed sites (Ser-202, Thr-181, and Thr-231) in systems enriched in alpha 7 nicotinic acetylcholine receptors (alpha 7nAChR) including serum-deprived human SK-N-MC neuroblastoma cells and hippocampal synaptosomes. Although alpha 7nAChR agonists induced similar phosphorylation, pretreatment with antisense-alpha 7nAChR oligonucleotides (in cells) or alpha 7nAChR antagonists (in cells and synaptosomes) attenuated A beta-induced tau phosphorylation. Western analyses showed that the mitogen-activated kinase cascade proteins, ERKs and c-Jun N-terminal kinase (JNK-1), were concomitantly activated by A beta 42, and their respective kinase inhibitors suppressed A beta-induced tau phosphorylation. More importantly, recombinant-activated ERKs and JNK-1 could differentially phosphorylate tau protein in vitro. Thus, the alpha 7nAChR may mediate A beta-induced tau protein phosphorylation via ERKs and JNK-1.
Novel Mammalian Cell Cycle Inhibitors, Tryprostatins A, B and Other Diketopiperazines Produced by Aspergillus fumigatus. I. Taxonomy, Fermentation, Isolation and Biological Properties. (1996)

Two novel diketopiperazines named tryprostatins A (1) and B (2) and a new natural product belonging to the diketopiperazine series, designated as demethoxyfumitremorgin C (3), together with four known diketopiperazines, fumitremorgin C (4), 12,13-dihydroxyfumitremorgin C (5), fumitremorgin B (6) and verruculogen (7), were isolated from the fermentation broth of Aspergillus fumigatus BM939 by the combined use of solvent extraction, silica gel column chromatography, preparative TLC and repeated-preparative HPLC. The diketopiperazines showed an inhibitory activity on the cell cycle progression of mouse tsFT210 cells in the M phase with the MIC values of 16.4 microM (1), 4.4 microM (2), 0.45 microM (3), 4.1 microM (4), 60.8 microM (5), 26.1 microM (6) and 12.2 microM (7), respectively.
cDNA sequences for human von Willebrand factor reveal five types of repeated domains and five possible protein sequence polymorphisms (1986)

A human umbilical vein endothelial cell cDNA library in lambda gt11 was screened with two previously described cDNA inserts for human von Willebrand factor. Among 16 positive isolates, two that hybridized with a probe corresponding to the amino terminus of von Willebrand factor were sequenced. Together, these four cDNA inserts span 6.5 kilobases of the von Willebrand factor mRNA sequence, completely specifying the 2050 amino acids of the subunit of mature, secreted von Willebrand factor and 24 residues of a precursor peptide. Approximately 77% of the sequence is contained in five types of repeated domains. Domain A consists of 193-220 amino acids and is present in three tandem copies between residues 497 and 1111. Domain B contains 25-35 amino acids and is present in three copies between residues 1533 and 1636. Domain C consists of 116-119 amino acids and is duplicated between residues 1637 and 1899. In contrast to the essentially contiguous repetition of domains A-C, the two copies of domains D and E are each separated by 804 and 1383 amino acids, respectively. Domain D1 contains 289 amino acids between residues 79 and 367, while domain D2 consists of 270 amino acids between residues 1171 and 1440. Domain E1 consists of 46 amino acids between residues 25 and 70, and domain E2 consists of 46 amino acids between residues 1453 and 1498. The triplicated A domains are notably poor in Cys content, while the remaining domains are Cys-rich. The A domains appear to be homologous to a 225-residue segment of complement factor B.(ABSTRACT TRUNCATED AT 250 WORDS)
Sorption Behavior of Citrus-Flavor Compounds in Polyethylenes and Polypropylenes (1991)

An understanding of the interactions between food ingredients and polymeric packaging materials requires knowledge of the chemical and physical structures of the food ingredients and of the polymers (1). This paper reports the behavior of citrus compounds with varied functional groups in model water solutions with polyolefins of three structural types: Unbranched high density polyethylene, branched low density polyethylene and two stereoregular polypropylenes. Included in the study are the partitioning behavior of a mixture of seven citrus flavor compounds and a comparison of the partition coefficients and Gibbs free energy changes of limonene and carvone representing compounds of similar structure but with different polarities. Mechanistic implications are drawn from the data on their interactions with these structurally different polyolefins.
[Clinical, radiologic and morphologic characteristics of localized forms of pulmonary tuberculosis. Tuberculosis and hypoplasia]. (1995)

Clinical and x-ray examinations and study of operation material from 555 patients with local forms of tuberculosis permitted the authors to distinguish three form of the condition: tuberculoma (77% of cases), cavitary (cavernous) tuberculosis (16%), and tuberculosis of the bronchi (5%). Morphologic investigations showed the local tuberculosis develops at small sites of pulmonary tissue hypoplasia. Sites of hypoplasia are usually concentrated in the pulmonary segments which are formed in the postnatal period, thus explaining the typical localization of a postprimary tuberculous focus. Tissue decomposition with development of destruction cavities is not characteristic of local tuberculosis. Cavitary (cavernous) form is a morphologic reflection of a tuberculous inflammation in the zone of cestous hypoplasia. Morphonesis of local forms of tuberculosis reflects its social dependence.
Reducing Codon Redundancy and Screening Effort of Combinatorial Protein Libraries Created by Saturation Mutagenesis (2012)

Saturation mutagenesis probes define sections of the vast protein sequence space. However, even if randomization is limited this way, the combinatorial numbers problem is severe. Because diversity is created at the codon level, codon redundancy is a crucial factor determining the necessary effort for library screening. Additionally, due to the probabilistic nature of the sampling process, oversampling is required to ensure library completeness as well as a high probability to encounter all unique variants. Our trick employs a special mixture of three primers, creating a degeneracy of 22 unique codons coding for the 20 canonical amino acids. Therefore, codon redundancy and subsequent screening effort is significantly reduced, and a balanced distribution of codon per amino acid is achieved, as demonstrated exemplarily for a library of cyclohexanone monooxygenase. We show that this strategy is suitable for any saturation mutagenesis methodology to generate less-redundant libraries.
Single Gold Nanoparticles Encapsulated in Monodispersed Regular Spheres of Mesostructured Silica Produced by Pseudomorphic Transformation (2007)

Monodispersed, uniform, gold encapsulated−mesoporous silica nanocomposites of 100−350 nm diameter with a centered metal core at about 15 or 30 nm and high gold occupancy are prepared by pseudomorphic transformation of preformed gold−silica nanospheres. The characterization by X-ray powder diffraction, transmission electron microscopy, 29Si and 13C magic angle spinning NMR, and N2 adsorption isotherms indicates that these materials present the same morphology and particle size distribution of the parent amorphous silica but with an ordered mesoporous shell of complex wormhole-like pore structure and specific surface area of about 1000 m2 g-1. This method is particularly advantageous for both stabilizing gold nanoparticles and tailoring structural and textural parameters of the outer shell, thus, offering an exceptional support for particle functionalization.
Total synthesis of (.+-.)-aspirochlorine (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal synthesis of (.+-.)-aspirochlorineGregory F. Miknis and Robert M. WilliamsCite this: J. Am. Chem. Soc. 1993, 115, 2, 536–547Publication Date (Print):January 1, 1993Publication History Published online1 May 2002Published inissue 1 January 1993https://pubs.acs.org/doi/10.1021/ja00055a025https://doi.org/10.1021/ja00055a025research-articleACS PublicationsRequest reuse permissionsArticle Views1402Altmetric-Citations57LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Hippocampal Damage and Exploratory Preferences in Rats: Memory for Objects, Places, and Contexts (2002)

Rats have a natural tendency to spend more time exploring novel objects than familiar objects, and this preference can be used as an index of object recognition. Rats also show an exploratory preference for objects in locations where they have not previously encountered objects (an index of place memory) and for familiar objects in contexts different from those in which the objects were originally encountered (an index of context memory). In this experiment, rats with cytotoxic lesions of the hippocampal formation were tested on all three versions of the novelty-preference paradigm, with a 5-min retention interval between the familiarization and test phases. Rats with sham lesions displayed a novelty preference on all three trial types, whereas the rats with hippocampal lesions displayed a novelty preference on Object trials but did not discriminate between the objects on Place trials or Context trials. The findings indicate that hippocampal damage impairs memory for contextual or spatial aspects of an experience, whereas memory for objects that were part of the same experience are left relatively intact.
Synthesis of Distributed Elliptic-Function Filters from Lumped-Constant Prototypes (1966)

A synthesis procedure for distributed elliptic-function filters utilizing published tables of lumped-constant elliptic-function filters has been devised. It is dependent upon the application of a new generalized transformation for distributed networks. The filters often require the realization of distributed Brune sections, and several novel practical realizations are given both for general and degenerate Brune (i.e., Foster) sections. Examples are given of elliptic function stop band and pass band filters having both wide and narrow bandwidths, and experimental results show good agreement with theory.
Protection from graft-versus-host disease by HIV-1 envelope protein gp120-mediated activation of human CD4+CD25+ regulatory T cells (2009)

Naturally occurring CD4(+)CD25(+) regulatory T cells (Tregs) represent a unique T-cell lineage that is endowed with the ability to actively suppress immune responses. Therefore, approaches to modulate Treg function in vivo could provide ways to enhance or reduce immune responses and lead to novel therapies. Here we show that the CD4 binding human immunodeficiency virus-1 envelope glycoprotein gp120 is a useful and potent tool for functional activation of human Tregs in vitro and in vivo. Gp120 activates human Tregs by binding and signaling through CD4. Upon stimulation with gp120, human Tregs accumulate cyclic adenosine monophosphate (cAMP) in their cytosol. Inhibition of endogeneous cAMP synthesis prevents gp120-mediated Treg activation. Employing a xenogeneic graft versus host disease model that has been shown to be applicable for the functional analysis of human Tregs in vivo, we further show that a single dose of gp120 is sufficient to prevent lethal graft versus host disease and that the tolerizing effect of gp120 is strictly dependent on the presence of human Tregs and their up-regulation of cAMP upon gp120-mediated activation. Our findings demonstrate that stimulation via the CD4 receptor represents a T-cell receptor-independent Treg activating pathway with potential to induce immunologic tolerance in vivo.