gebhart/patrepeval huggingface dataset:
Synthesis and Characterization of Lipid–Polymer Hybrid Nanoparticles with pH-Triggered Poly(ethylene glycol) Shedding (2011)

Novel lipid-polymer hybrid nanoparticles are designed with a poly(ethylene glycol) (PEG) coating that is shed in response to a low pH trigger. This allows the nanoparticles to be stable during systemic circulation and at neutral pH, but destabilize and fuse with lipid membranes in acidic environments. The hybrid nanoparticles consist of a poly(lactic-co-glycolic acid) core with a lipid and lipid-PEG monolayer shell. To make the hybrid nanoparticles pH sensitive, a lipid-(succinate)-mPEG conjugate is synthesized to provide a hydrolyzable PEG stealth layer that is shed off the particle surface at low pH. The pH-sensitivity of the nanoparticles is tunable using the molar concentration of the lipid-(succinate)-mPEG incorporated in the lipid shell of the particles. Possible uses of these pH-sensitive nanoparticles include aggregating in acidic tumor microenvironments, escaping acidified endosomes, or aggregating in deep lung tissue for improved inhalation administration.
Adaptive multiple subtraction: Unification and comparison of matching filters based on the ℓq-norm and statistical independence (2015)

ABSTRACT An adaptive multiple subtraction step is necessary for almost all methods that predict seismic multiple reflected waves. We aim at giving a better understanding of matching filters based on ℓq-norms and on statistical independence. We found that the formulation of all of these techniques can be gathered in a mutual framework by introducing a space-time operator, called the primary enhancer, acting on the estimated primaries. The differences between the considered matching filters become more intuitive because this operator behaves as a simple amplitude compressor. In this perspective, all the methods tend to uncorrelate the predicted multiples and the enhanced estimated primaries. The study of these matching-filter methods can be narrowed to the study of the primary enhancer operator because it is the only difference. Moreover, we have emphasized the role of using adjacent traces or windowing approaches in terms of statistics, and we show that an adequate windowing strategy may overbear the choice of the objective function. Indeed, our analysis showed that setting a good windowing strategy may be more important than changing the classical least-squares adaptation criterion to other approaches based on ℓq-norm minimization or independent component analysis.
A Fluorescent Indicator To Visualize Activities of the Androgen Receptor Ligands in Single Living Cells (2006)

Seeing the light: An androgen promotes interactions between the androgen-receptor ligand-binding domain (AR LBD) and a coactivator protein. This results in an increase in the fluorescence resonant energy transfer (FRET) from cyan fluorescent protein (CFP) to yellow fluorescent protein (YFP). The indicator distinguishes ligands of different potencies for the AR.
VESTIBULAR REHABILITATION (2006)

Account Register Activate Subscription Help Subscribe American Academy of Neurology Login Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. Subscribe to eTOC Journal logo Issues Current IssueBack Issues CollectionsMedia Continuum AudioVideo Gallery CMEAbout About ContinuumAbout Continuum AudioSubscription Details and AccessEditorial BoardEditorial and Publishing ContactsInformation for AuthorsAAN/WFN Continuum EducationAbout AANRights and PermissionsReprints
Functional Assays for Identifying Ligands at Orphan G Protein-Coupled Receptors (2002)

The superfamily of G protein-coupled receptors (GPCRs; 7TMs) is one of the largest families of genes identified in humans, and has a proven history of being an excellent source of drug targets. The near completion of the human genome sequencing project has allowed the identification of a plethora of sequences encoding "orphan" GPCRs--putative receptors whose natural ligand(s) remain to be discovered. In many cases, the level of sequence homology with known receptors is insufficient to be able to predict the natural ligand for these orphan receptors, although it is usually possible to determine the likely nature of the cognate ligand e.g. peptide, lipid, nucleotide etc. Deorphanizing these novel GPCRs and evaluating their biological function has become a major target of many of the major pharmaceutical companies as well as several academic groups. Since 1995 more than 50 ligands for orphan GPCRs have been discovered by using the orphan receptor as a biosensor and screening candidate compounds looking for a biological response (the so-called "reverse pharmacology" approach). Identification of the natural ligands for these receptors marks the beginning of the process of understanding the biology of these newly discovered signalling systems and the development of novel therapies targetted at them. This article will focus on the functional assays which have been used to discover ligands for orphan GPCRs.
Nucleic acid related compounds. 47. Synthesis and biological activities of pyrimidine and purine "acyclic" nucleoside analogs (1984)

Various acyclic, i.e., (2-hydroxyethoxy)methyl and (2-acetoxyethoxy)methyl, analogues of pyrimidine and purine nucleosides have been prepared and evaluated for their antiviral, antimetabolic, and cytotoxic properties. All of the pyrimidine analogues, including (E)-5-(2-bromovinyl)-1-[(2-hydroxyethoxy)methyl]uracil (12) and its O-acetyl derivative (13), were virtually devoid of antiviral, cytotoxic, and antimetabolic activities. However, several of the 8-substituted derivatives of 9-[(2-hydroxyethoxy)methyl]guanine (acyclovir) had higher antiviral specificity in vitro than the parent drug. The 8-methyl-, 8-amino-, 8-bromo-, and 8-iodoacyclovir derivatives have activities worthy of further investigation.
Atrial, B-type, and C-type natriuretic peptides cause mesenteric vasoconstriction in conscious dogs (1999)

Cardiovascular responses were compared with equimolar infusions of B-type (BNP) and C-type (CNP) with atrial natriuretic peptide (ANP) in conscious, instrumented dogs. On separate days, each natriuretic peptide or vehicle was infused (intravenously) at step-up doses of 2, 5, 10, and 20 pmol. kg-1. min-1 (20 min each dose) to increase circulating levels of the infused peptide from approximately 2- to 20-fold. Like ANP, infusions of BNP caused dose-related increases (P < 0.05) in mesenteric vascular resistance, urine flow, natriuresis, and hematocrit (changes at highest doses were 60 +/- 9, 334 +/- 113, 313 +/- 173, and 12 +/- 2%, respectively). BNP also lowered (P < 0. 05) plasma renin activity (-43 +/- 11%) and arterial pressure (-10 +/- 3%). Effects of BNP were independent of reflex sympathetic activation, since autonomic ganglion blockade did not attenuate the responses. CNP infusions had little effect except to increase (P < 0. 05) mesenteric vascular resistance (27 +/- 10%) and plasma ANP (41 +/- 7%). Cardiovascular actions of BNP, like those of ANP, counteract the renin-ANG system and may protect the heart by lowering cardiac preload (venous return) and afterload (arterial pressure) while maintaining blood flow to extrasplanchnic regions.
Effect of tunicamycin on herpes simplex virus glycoproteins and infectious virus production (1980)

The antibiotic tunicamycin, which blocks the synthesis of glycoproteins, inhibited the production of infectious herpes simplex virus. In the presence of this drug, [14C]glucosamine and [3H]mannose incorporation was reduced in infected cells, whereas total protein synthesis was not affected. Gel electrophoresis of [2-3H]mannose-labeled polypeptides failed to detect glycoprotein D or any of the other herpes simplex virus glycoproteins. By use of specific antisera we demonstrated that in the presence of tunicamycin the normal precursors to viral glycoproteins failed to appear. Instead, lower-molecular-weight polypeptides were found which were antigenically and structurally related to the glycosylated proteins. Evidence is presented to show that blocking the addition of carbohydrate to glycoprotein precursors with tunicamycin results in the disappearance of molecules, possibly due to degradation of the unglycosylated polypeptides. We infer that the added carbohydrate either stabilizes the envelope proteins or provides the proper structure for correct processing of the molecules needed for infectivity.
Reactivation of latent infection and induction of recurrent herpetic eye disease in mice (1990)

During primary ocular infection of mice with herpes simplex virus type 1 (HSV-1) strain McKrae, dendritic corneal ulcers developed and many eyes became permanently damaged. When primary infection had subsided, latent infection was detected in the three parts of the trigeminal ganglion and in the superior cervical ganglion. Such latently infected mice were treated with cyclophosphamide, dexamethasone and u.v. irradiation, or cyclophosphamide and dexamethasone alone. After treatment with immunosuppressive drugs and u.v. irradiation infectious virus was isolated from the ophthalmic part of the trigeminal ganglion, and in eyelids and eyewashings; recurrent herpetic eye disease was seen but only in eyes undamaged by primary infection. After treatment with cyclophosphamide and dexamethasone alone there was a lower incidence of virus isolated from eyewashings and no recurrent disease was seen. There was a good correlation between the pattern and distribution of recurrent lesions and the distribution of cells stained due to the presence of virus antigens.
Vitamin D receptor gene polymorphism and prostate cancer risk (2002)

In this case-control study of Austrian Caucasians, no statistically significant association of the VDR TaqI polymorphism and prostate cancer risk was found.
S-FTL: An efficient address translation for flash memory by exploiting spatial locality (2011)

The solid-state disk (SSD) is becoming increasingly popular, especially among users whose workloads exhibit substantial random access patterns. As SSD competes with the hard disk, whose per-GB cost keeps dramatically falling, the SSD must retain its performance advantages even with low-cost configurations, such as those with a small built-in DRAM cache for mapping table and using MLC NAND. To this end, we need to make the limited cache space efficiently used to support fast logical-to-physical address translation in the flash translation layer (FTL) with minimal access of flash memory and minimal merge operations. Existing schemes usually require a large number of overhead accesses, either for accessing uncached entries of the mapping table or for the merge operation, and achieve suboptimal performance when the cache space is limited. In this paper we take into account spatial locality exhibited in the workloads to obtain a highly efficient FTL even with a relatively small cache, named as S-FTL. Specifically, we identify three access patterns related to spatial locality, including sequential writes, clustered access, and sparse writes. Accordingly we propose designs to take advantage of these patterns to reduce mapping table size, increase hit ratio for in-cache address translation, and minimize expensive writes to flash memory. We have conducted extensive trace-driven simulations to evaluate S-FTL and compared it with other state-of-the-art FTL schemes. Our experiments show that S-FTL can reduce accesses to the flash for address translation by up to 70% and reduce response time of SSD by up to 25%, compared with the state-of-the-art FTL strategies such as FAST and DFTL.
Plagiarism in programming assignments (1999)

The assessment of programming courses is usually carried out by means of programming assignments. Since it is simple to copy and edit computer programs, however, there will always be a temptation among some students following such courses to copy and modify the work of others. As the number of students in these courses is often high, it can be very difficult to detect this plagiarism. The authors have developed a package which will allow programming assignments to be submitted online, and which includes software to assist in detecting possible instances of plagiarism. In this paper, they discuss the concerns that motivated this work, describe the developed software, tailoring the software to different requirements and finally consider its implications for large group teaching.
Review Oncologic, Endocrine & Metabolic: Recent developments in matrix metalloproteinase inhibitors (1995)

The matrix metalloproteinases (MMPs) are a family of endopeptidases that are involved in the degradation and remodelling of the extracellular matrix of connective tissues and basement membranes. There is increasing evidence that these molecules are involved in a variety of degradative diseases such as arthritis and cancer. This review summarises recent developments in the design and application of small molecule MMP inhibitors disclosed in the recent patent and primary literature.
Taxonomy of neural transfer functions (2000)

The choice of transfer functions may strongly influence complexity and performance of neural networks used in classification and approximation tasks. A taxonomy of activation and output functions is proposed, allowing to generate many transfer functions. Several less-known types of transfer functions and new combinations of activation/output functions are described. Functions parameterize to change from localized to delocalized type, functions with activation based on nonEuclidean distance measures, bicentral functions formed from pairs of sigmoids are discussed.
Hemagglutinin (HA) Proteins from H1 and H3 Serotypes of Influenza A Viruses Require Different Antigen Designs for the Induction of Optimal Protective Antibody Responses as Studied by Codon-Optimized HA DNA Vaccines (2006)

Effective antibody responses provide crucial immunity against influenza virus infection. The hemagglutinin (HA) protein is the major target of protective antibody responses induced by viral infection and by vaccination with both inactivated and live-attenuated flu vaccines, but knowledge about the optimal designs of protective HA antigens from different flu serotypes is still limited. In this study, we have significantly improved the immunogenicity of HA-expressing DNA vaccines by using codon-optimized HA sequences for either an H1 serotype (A/NewCal/20/99) or an H3 serotype (A/Panama/2007/99) human influenza A virus and then used these constructs as model antigens to identify the optimal HA antigen designs to elicit high-level protective antibody responses. Two forms of HA antigen, a wild-type, full-length HA and a secreted form with transmembrane (TM) domain-truncated HA, were produced. Both forms of HA DNA vaccines, from either H1 or H3 serotypes, were able to elicit high levels of HA-specific immunoglobulin G responses in immunized rabbits as measured by enzyme-linked immunosorbent assay. Interestingly, the abilities of H1 HA and H3 HA antigens to elicit hemagglutination inhibition (HI) and neutralizing antibody (NAb) responses differ. For the H1 HA antigens, the full-length HA induced significantly higher HI and NAb responses than did the TM-truncated HA. For the H3 HA antigen, both the full-length HA and TM-truncated HA induced high levels of HI and NAb responses. These data indicate that H1 and H3 antigens have different expression requirements for the induction of an optimal protective antibody response and that the structure integrity of HA antigens is critical for eliciting type-specific protective antibody responses. Our findings will have an important impact on future subunit-based flu vaccine development.
711. Allele-Specific Silencing of Mutant Huntingtin for Huntington's Disease Therapy (2006)

Huntington's disease (HD) is a dominant genetic neurodegenerative disease. Studies in a tetracycline-responsive mouse model showed that continuous expression of the mutant allele is required for the development of behavioral and pathological symptoms; when mutant huntingtin expression was turned off, disease phenotypes resolved. More recently, gene therapy approaches using interference RNA (RNAi) in HD mouse models successfully prevented HD phenotypes. Because we do not know if reduction of both normal and mutant huntingtin alleles will be tolerated in humans, we investigated an allele-specific RNAi approach for HD. Here we show two different strategies for specific silencing of the mutant huntingtin allele. One is based on structural changes of the mutant huntingtin mRNA as a consequence of the massive CAG-expansion within exon 1 relative to the wild type allele. A second approach is based on a polymorphism in exon 58 that reportedly resides in 40% of mutant huntingtin alleles in a sample South American population. To perform our analyses, we developed a novel assay design. Briefly, we generated two plasmids expressing full-length wild type or mutant huntingtin (CAG expansion in exon 1 plus exon 58 polymorphism), each possessing distinct epitope tags and either renilla (WT htt) or firefly (mutant htt) luciferase to normalize transfection efficiencies. This design allowed us to assess allele specificity in the same cell after co-transfection. Sequences of short interfering RNA (siRNA) targeting 5′ and 3′ of the CAG-repeat region, or the exon 58 polymorphism, were generated; some siRNA sequences were altered according to recent guide-strand rules for optimized RISC loading. Our initial studies with sequences targeting either the exon-58 polymorphism or the CAG repeat region showed specific silencing of the mutant allele. With some siRNAs, mutant protein levels were reduced to 60% with no reduction in wildtype protein levels. Other siRNAs preferentially silenced the mutant huntingtin allele up to 70% while reducing wild type protein levels to only 30% of control values. Together, our data indicate that targeting sequences flanking the CAG-repeat expansion region in exon-1, or the polymorphism in exon 58, may be viable strategies for allele specific silencing for HD therapy.
Soybean isoflavones: effect of environment and variety on composition (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSoybean isoflavones: effect of environment and variety on compositionArthur C. Eldridge and William F. KwolekCite this: J. Agric. Food Chem. 1983, 31, 2, 394–396Publication Date (Print):March 1, 1983Publication History Published online1 May 2002Published inissue 1 March 1983https://pubs.acs.org/doi/10.1021/jf00116a052https://doi.org/10.1021/jf00116a052research-articleACS PublicationsRequest reuse permissionsArticle Views1141Altmetric-Citations268LEARN 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-Alertsclose Get e-Alerts
Peptide Recognition by Two HLA-A2/Tax11–19-Specific T Cell Clones in Relationship to Their MHC/Peptide/TCR Crystal Structures (1999)

The crystal structures of two human TCRs specific for a HTLV-I Tax peptide bound to HLA-A2 were recently determined, for the first time allowing a functional comparison of TCRs for which the MHC/peptide/TCR structures are known. Extensive amino acid substitutions show that the native Tax residues are optimal at each peptide position. A prominent feature of the TCR contact surface is a deep pocket that accommodates a tyrosine at position 5 of the peptide. For one of these TCRs, this pocket is highly specific for aromatic residues. In the other TCR structure, this pocket is larger, allowing many different residues to be accommodated. The CTL clones also show major differences in the specificity for several other peptide residues, including side chains that are not directly contacted by the TCR. Despite the specificity of these clones, peptides that are distinct at five or six positions from Tax11-19 induce CTL activity, indicating that substantial changes of the peptide surface are tolerated. Human peptides with limited sequence homology to Tax11-19 represent partial TCR agonists for these CTL clones. The distinct functional properties of these CTL clones highlight structural features that determine TCR specificity and cross-reactivity for MHC-bound peptides.
Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract (2009)

Populations of interstitial cells of Cajal (ICC) are altered in several gastrointestinal neuromuscular disorders. ICC are identified typically by ultrastructure and expression of Kit (CD117), a protein that is also expressed on mast cells. No other molecular marker currently exists to independently identify ICC. The expression of ANO1 (DOG1, TMEM16A), a Ca(2+)-activated Cl(-) channel, in gastrointestinal stromal tumors suggests it may be useful as an ICC marker. The aims of this study were therefore to determine the distribution of Ano1 immunoreactivity compared with Kit and to establish whether Ano1 is a reliable marker for human and mouse ICC. Expression of Ano1 in human and mouse stomach, small intestine, and colon was investigated by immunofluorescence labeling using antibodies to Ano1 alone and in combination with antibodies to Kit. Colocalization of immunoreactivity was demonstrated by epifluorescence and confocal microscopy. In the muscularis propria, Ano1 immunoreactivity was restricted to cells with the morphology and distribution of ICC. All Ano1-positive cells in the muscularis propria were also Kit positive. Kit-expressing mast cells were not Ano1 positive. Some non-ICC in the mucosa and submucosa of human tissues were Ano1 positive but Kit negative. A few (3.2%) Ano1-positive cells in the human gastric muscularis propria were labeled weakly for Kit. Ano1 labels all classes of ICC and represents a highly specific marker for studying the distribution of ICC in mouse and human tissues with an advantage over Kit since it does not label mast cells.
Modernes Management eines Radiologischen Imaging Centers - (2009)

Vom „Kostenverursacher“ zum „Profit Center“– vom festen Budget über die flexible Plankostenrechnung zum Benchmarking an DRG-Anteilen -