gebhart/patrepeval huggingface dataset:
Development of enteric submicron particle formulation of papain for oral delivery (2011)

In simulated gastrointestinal pH conditions, the HPMCP, Eudragit L100, and Eudragit S100 submicron particles showed good digestion of paneer and milk protein, and could serve as potential carriers for oral enzyme delivery. Stability studies indicated that formulations with approximately 6% overage would ensure a two-year shelf-life at room temperature.
Assessing kinetic and epitopic diversity across orthogonal monoclonal antibody generation platforms (2015)

The ability of monoclonal antibodies (mAbs) to target specific antigens with high precision has led to an increasing demand to generate them for therapeutic use in many disease areas. Historically, the discovery of therapeutic mAbs has relied upon the immunization of mammals and various in vitro display technologies. While the routine immunization of rodents yields clones that are stable in serum and have been selected against vast arrays of endogenous, non-target self-antigens, it is often difficult to obtain species cross-reactive mAbs owing to the generally high sequence similarity shared across human antigens and their mammalian orthologs. In vitro display technologies bypass this limitation, but lack an in vivo screening mechanism, and thus may potentially generate mAbs with undesirable binding specificity and stability issues. Chicken immunization is emerging as an attractive mAb discovery method because it combines the benefits of both in vivo and in vitro display methods. Since chickens are phylogenetically separated from mammals, their proteins share less sequence homology with those of humans, so human proteins are often immunogenic and can readily elicit rodent cross-reactive clones, which are necessary for in vivo proof of mechanism studies. Here, we compare the binding characteristics of mAbs isolated from chicken immunization, mouse immunization, and phage display of human antibody libraries. Our results show that chicken-derived mAbs not only recapitulate the kinetic diversity of mAbs sourced from other methods, but appear to offer an expanded repertoire of epitopes. Further, chicken-derived mAbs can bind their native serum antigen with very high affinity, highlighting their therapeutic potential.
Role of Repetitive Antigen Patterns for Induction of Antibodies Against Antibodies (1997)

Antibody responses against antibodies, such as rheumatoid factors, are found in several immunopathological diseases and may play a role in disease pathogenesis. Experience shows that they are usually difficult to induce experimentally. Antibodies specific for immunoglobulin constant regions (anti-allotypic) or for variable regions (anti-idiotypic) have been investigated in animal models; the latter have even been postulated to regulate antibody and T cell responses via network-like interactions. Why and how such anti-antibodies are induced during autoimmune diseases, has remained largely unclear. Because repetitively arranged epitopes in a paracrystalline structure of a viral envelope cross-link B cell receptors efficiently to induce a prompt T-independent IgM response, this study used immune complexes containing viruses or bacteria to evaluate the role of antigen pattern for induction of anti-antibody responses. We present evidence that antibodies bound to strictly ordered, but not to irregularly arranged, antigens dramatically enhance induction of anti-antibodies, already after a single immunization and without using adjuvants. The results indicate a novel link between anti-antibody responses and infectious agents, and suggest a similar role for repetitive self-antigens such as DNA or collagen involved in chronic immunopathological diseases.
Applications of Acoustics and Cavitation to Noninvasive Therapy and Drug Delivery (2008)

Biomedical acoustics is rapidly evolving from a diagnostic modality into a therapeutic tool, and acoustic cavitation is often the common denominator in a wide range of new therapeutic applications. High-intensity focused ultrasound (HIFU) waves generated outside the body can be used to deposit heat deep within the body. Through a quantitative analysis of heat deposition by ultrasound, it is shown that inertial cavitation can help address some of the major challenges of HIFU therapy by providing a means of enhancing and monitoring treatment noninvasively. In the context of drug delivery, both inertial and stable cavitation play roles in enhancing drug activity and uptake. In particular, shape oscillations arising during stable cavitation provide an effective micropumping mechanism for enhanced mass transport across inaccessible interfaces.
Ligand-Binding Enhances the Affinity of Dimerization of the Extracellular Domain of the Epidermal Growth Factor Receptor (1997)

We studied the dimerization of the recombinant soluble extracellular domain of the epidermal growth factor receptor (sEGFR) in response to EGF-binding using multi-angle laser light scattering with size exclusion chromatography (SEC-MALLS). In the absence of EGF, sEGFR behaved as a monomer. However, upon EGF-binding, sEGFR formed a dimer with the stoichiometry of two EGF molecules bound to two sEGFR molecules [(EGF)2-(sEGFR)2]. We analyzed the chemical equilibrium of the dimer formation by SEC-MALLS using a dissociation constant of 0.25 microM for the binding of EGF to sEGFR. The calculated dissociation constant for EGF-induced sEGFR dimerization was found to be 2.4 +/- 0.9 microM. These experiments demonstrated that EGF induces receptor dimerization and that two EGF molecules are bound to an EGF-receptor dimer.
Metabolism, distribution and excretion of purified human chorionic gonadotropin and its subunits in man. (1984)

We have characterized the distribution, metabolism and excretion of hCG and its subunits in normal human subjects. The initial apparent volume of distribution was the same for hCG, hCG beta, and hCG alpha. Their disappearance curves fit a two-component exponential model, and calculations indicated that both the rapid and slow phase half-times of hCG are approximately 10-fold greater than those of hCG beta and 30-fold greater than those of hCG alpha. Despite the more rapid metabolic clearance rates of the subunits, their renal clearance is 2- to 3-fold less than that of hCG. Thus, renal clearance accounts for less than 1% of the metabolic disposal of the subunits, whereas it represents a major fraction (20-25%) of the metabolic disposal of hCG. After injection of the isolated beta subunit of hCG, two forms were excreted in the urine. One was intact hCG beta and the other was a discrete fragment of the hCG beta which appears to lack the hCG beta carboxyterminal peptide immunologic determinant; we have termed this later material an hCG beta core fragment.
Body Temperature Changes During Prostatic Resection as Related to the Temperature of the Irrigating Solution (1973)

No AccessJournal of Urology1 Oct 1973Body Temperature Changes During Prostatic Resection as Related to the Temperature of the Irrigating Solution Terry D. Allen Terry D. AllenTerry D. Allen View All Author Informationhttps://doi.org/10.1016/S0022-5347(17)60242-8AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail © 1973 by The American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byEvans J, Singer M, Coppinger S, Macartney N, Walker J and Milroy E (2018) Cardiovascular Performance and Core Temperature During Transurethral ProstatectomyJournal of Urology, VOL. 152, NO. 6 Part 1, (2025-2029), Online publication date: 1-Dec-1994. Volume 110Issue 4October 1973Page: 433-435 Advertisement Copyright & Permissions© 1973 by The American Urological Association Education and Research, Inc.MetricsAuthor Information Terry D. Allen More articles by this author Expand All Advertisement PDF downloadLoading ...
Controlled Encapsulation of Hydrophobic Liquids in Hydrophilic Polymer Nanofibers by Co‐electrospinning (2006)

Abstract There are many technical situations, such as various biological or medical applications, in which a hydrophobic fluid must be encapsulated inside a hydrophilic polymer shell in the form of tiny microscopic pieces. A novel approach is presented, based on the co‐electrospinning of the hydrophilic polymer melt (outside) and the hydrophobic fluid (inside), which results in beaded micro‐ and nanofibers, such that the hydrophobic fluid is efficiently encapsulated inside the beads. For the selected fluid couple, the low liquid–liquid surface tension and the high viscosity of the melt prevent the varicose break‐up of inner fluid in the coaxial electrified jet until the very end of the co‐electrospinning process. The resulting fibers present beads filled with the hydrophobic fluid, separated by a rather uniform distance whose length depends partially on the melt flow rate. The bead diameter grows with the inner flow rate, going from a monosized to a bisized distribution. In the case under study, the maximum relative (inner‐to‐outer) flow rate is one. The diameter of the solid fibers between beads scales well with existing theories for simple electrospinning.
DNA Cloning Using In Vitro Site-Specific Recombination (2000)

As a result of numerous genome sequencing projects, large numbers of candidate open reading frames are being identified, many of which have no known function. Analysis of these genes typically involves the transfer of DNA segments into a variety of vector backgrounds for protein expression and functional analysis. We describe a method called recombinational cloning that uses in vitro site-specific recombination to accomplish the directional cloning of PCR products and the subsequent automatic subcloning of the DNA segment into new vector backbones at high efficiency. Numerous DNA segments can be transferred in parallel into many different vector backgrounds, providing an approach to high-throughput, in-depth functional analysis of genes and rapid optimization of protein expression. The resulting subclones maintain orientation and reading frame register, allowing amino- and carboxy-terminal translation fusions to be generated. In this paper, we outline the concepts of this approach and provide several examples that highlight some of its potential.
Phenotypic analysis of synovial tissue and peripheral blood lymphocytes isolated from patients with rheumatoid arthritis (1988)

Cytofluorometric analysis was performed to characterize the surface phenotype and activation status of freshly isolated synovial tissue lymphocytes (STL) and peripheral blood lymphocytes (PBL) from 7 patients with rheumatoid arthritis (RA). Proliferative synovium was enzymatically digested to obtain tissue-derived lymphocytes. Indirect immunofluorescent staining of patient PBL and STL with a variety of monoclonal antibodies failed to reveal a consistent alteration in the number of CD4+ (helper/inducer) PBL or STL. However, there was a significant decrease in the number of CD8+ (suppressor/cytotoxic) cells in rheumatoid STL (P less than 0.05). A significant reduction in the density of the T cell differentiation antigens CD3 and CD4 was observed in RA PBL and STL, compared with control PBL. These differences in antigen density were not seen when normal PBL were subjected to the same enzymatic digestion. Both RA PBL and STL manifested increased expression of HLA-DR antigens, without augmentation of interleukin-2 receptor expression. Alterations in the expression of the T cell differentiation antigens and activation antigens by patient PBL closely paralleled the abnormalities observed in STL. In contrast, STL of patients with RA exhibited an increase in the expression of the adhesion-related glycoproteins (leukocyte function-associated 1 [LFA-1] and very late activation 1 [VLA-1] antigens), not observed with autologous PBL. These studies demonstrate that lymphocytes isolated from the synovial tissues of RA patients bear an activated phenotype, exemplified by the modulation of CD3 and CD4 and the expression of HLA-DR.(ABSTRACT TRUNCATED AT 250 WORDS)
Evidence for Functional Relevance of CTLA-4 in Ultraviolet-Radiation-Induced Tolerance (2000)

Hapten sensitization through UV-exposed skin induces hapten-specific tolerance that can be adoptively transferred by injecting T lymphocytes into naive recipients. The exact phenotype of T cells responsible for inhibiting the immune response and their mode of action remain unclear. Evidence exists that CTLA-4 negatively regulates T cell activation. We addressed whether CTLA-4 is involved in the transfer of UV-induced tolerance. Injection of lymph node cells from mice that were sensitized with dinitrofluorobenzene (DNFB) through UV-irradiated skin inhibited induction of contact hypersensitivity against DNFB in the recipient animals. When CTLA-4+ cells were depleted, transfer of suppression was lost. Likewise, significantly fewer lymphocytes enriched for CTLA-4+ cells were necessary to transfer suppression than unfractionated cells. Expression of CTLA-4 appears to be functionally relevant, since in vivo injection of a blocking anti-CTLA-4 Ab was able to break UV-induced tolerance and inhibited transfer of suppression. Upon stimulation with dendritic cells in the presence of the water-soluble DNFB analogue, DNBS, CTLA-4+ T cells from DNFB-tolerized mice secreted high levels of IL-10, TGF-beta, and IFN-gamma; low levels of IL-2; and no IL-4, resembling the cytokine pattern of T regulatory 1 cells. Ab blocking of CTLA-4 resulted in inhibition of IL-10 release. Accordingly, transfer of tolerance was not observed when recipients were treated with an anti-IL-10 Ab. Hence we propose that T cells, possibly of the T regulatory 1 type, transfer UV-mediated suppression through the release of IL-10. Activation of CTLA-4 appears to be important in this process.
Treatment of Fabry Disease: Outcome of a Comparative Trial with Agalsidase Alfa or Beta at a Dose of 0.2 mg/kg (2007)

Background. Two different enzyme preparations, agalsidase alfa (Replagal TM , Shire) and beta (Fabrazyme TM , Genzyme), are registered for treatment of Fabry disease. We compared the efficacy of and tolerability towards the two agalsidase preparations administered at identical protein dose in a randomized controlled open label trial. Methodology/Principal Findings. Thirty-four Fabry disease patients were treated with either agalsidase alfa or agalsidase beta at equal dose of 0.2 mg/kg biweekly. Primary endpoint was reduction in left ventricular mass after 12 and 24 months of treatment. Other endpoints included occurrence of treatment failure (defined as progression of cardiac, renal or cerebral disease), glomerular filtration rate, pain, anti-agalsidase antibodies, and globotriaosylceramide levels in plasma and urine. After 12 and 24 months of treatment no reduction in left ventricular mass was seen, which was not different between the two treatment groups. Also, no differences in glomerular filtration rate, pain and decline in globotriaosylceramide levels were found. Antibodies developed only in males (4/8 in the agalsidase alfa group and 6/8 in the agalsidase beta group). Treatment failure within 24 months of therapy was seen in 8/34 patients: 6 male patients (3 in each treatment group) and 2 female patients (both agalsidase alfa). The occurrence of treatment failures did not differ between the two treatment groups; x 2 = 0.38 p = 0.54. Conclusion. Our study revealed no difference in reduction of left ventricular mass or other disease parameters after 12 and 24 months of treatment with either agalsidase alfa or beta at a dose of 0.2 mg/kg biweekly. Treatment failure occurred frequently in both groups and seems related to age and severe pre-treatment disease. Trial Registration.
Evolution of Fucosyltransferase Genes in Vertebrates (1997)

Cloning and expression of chimpanzee FUT3, FUT5, and FUT6 genes confirmed the hypothesis that the gene duplications at the origin of the present human cluster of genes occurred between: (i) the great mammalian radiation 80 million years ago and (ii) the separation of man and chimpanzee 10 million years ago. The phylogeny of fucosyltransferase genes was completed by the addition of the FUT8 family of alpha(1,6)fucosyltransferase genes, which are the oldest genes of the fucosyltransferase family. By analysis of data banks, a new FUT8 alternative splice expressed in human retina was identified, which allowed mapping the human FUT8 gene to 14q23. The results suggest that the fucosyltransferase genes have evolved by successive duplications, followed by translocations, and divergent evolution from a single ancestral gene.
Comparative Effects of Lovastatin and Niacin in Primary Hypercholesterolemia (1994)

Lovastatin and niacin both exerted favorable dose-dependent changes on the concentrations of plasma lipids and lipoproteins. Lovastatin was more effective in reducing LDL cholesterol concentrations, whereas niacin was more effective in increasing high-density lipoprotein cholesterol concentrations and reducing the Lp(a) lipoprotein level. Lovastatin was better tolerated than niacin, in large part because of the common cutaneous side effects of niacin.
Ex Vivo-activated Human Macrophages Kill Chronic Lymphocytic Leukemia Cells in the Presence of Rituximab: Mechanism of Antibody-dependent Cellular Cytotoxicity and Impact of Human Serum (2006)

Antibody-dependent cellular cytotoxicity (ADCC) is one of the mechanisms of tumor killing during antibody (Ab) immunotherapy, and a role for myeloid cells as effectors has been observed in several models. We are developing immunotherapy approaches based on administration of large numbers of ex vivo interferon-gamma-activated macrophages to cancer patients. With a quantitative assay measuring killing of nonproliferating tumor cells, we evaluated whether, in physiologic conditions, these macrophages synergize with the anti-CD20 Ab rituximab for killing primary B-cell chronic lymphocytic leukemia (B-CLL) cells. ADCC reached levels of 70% to 80% at effector to target ratios as low as 1:1. Macrophage recruitment by Ab-opsonized tumor cells did not result in enhanced cytokine secretion, suggesting that the cytokine shower observed in rituximab-treated patients is not caused by macrophage activation, and that cytokines have no role in CLL killing. We observed that uptake of tumor material by macrophages was not directly correlated to tumor killing. Nonetheless, experiments in the presence of cytochalasin D showed that ADCC occurred mainly by phagocytosis. Tumor killing was largely mediated by Fc gammaRI and inhibited by increasing concentration of serum. Importantly, complement deposition on B-CLL cells did not seem to enhance macrophage ADCC in this model, as complement-depleted and complement-repleted human plasmas exerted comparable inhibition.
Highly enantioselective and substrate-selective polymers obtained by molecular imprinting utilizing noncovalent interactions. NMR and chromatographic studies on the nature of recognition (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHighly enantioselective and substrate-selective polymers obtained by molecular imprinting utilizing noncovalent interactions. NMR and chromatographic studies on the nature of recognitionBoerje. Sellergren, Matti. Lepistoe, and Klaus. MosbachCite this: J. Am. Chem. Soc. 1988, 110, 17, 5853–5860Publication Date (Print):August 1, 1988Publication History Published online1 May 2002Published inissue 1 August 1988https://pubs.acs.org/doi/10.1021/ja00225a041https://doi.org/10.1021/ja00225a041research-articleACS PublicationsRequest reuse permissionsArticle Views1651Altmetric-Citations458LEARN 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
The Hetero-Cope Rearrangement in Organic Synthesis (1989)

1. Introduction 2. Claisen Rearrangements 2.1. Methods of Preparation for Claisen Systems 2.2. Stereoselections 2.2.1. Cyclic Substrates 2.2.2. Acyclic Substrates 2.3. Rearrangements Accelerated by Charge 3. Aza-Cope Rearrangements 3.1. Amino-Claisen Rearrangements 3.2. 2-Aza-Cope Rearrangements 3.3. 1-Aza-Cope Rearrangements 4. 1-Aza-1′-Oxa-Cope Rearrangements 5. Miscellaneous Hetero-Cope Rearrangements This review presents a number of different variants of hetero-Cope rearrangements that have recently played an important role in organic syntheses. Modern developments concerning stereoselective and stereospecific syntheses are presented. Besides the possibilities of stereoselections, the applicability of efficient rearrangements in the course of establishing new functionalities and their use in tandem reactions is described.
Rapid acquisition for ultra-wideband localizers (2003)

Ultra-wideband (UWB) signals as implemented in our localizers provide a foundation for highly accurate methods of 3D position determination using precise ranging between any two nodes. In a large, distributed network of nodes, the time required for all nodes to acquire each other is of paramount importance. We have developed a method of rapid acquisition that allows two nodes to acquire each other in a fraction of the time afforded by other methods. We utilize a beacon/listener technique using Kasami sequences and divide-and-conquer algorithms to effect acquisitions in less than a second. We discuss our rapid acquisition process in this paper.
Formation of 2,3-dihydro-4(1H)-quinolones and related compounds via Fries-type acid-catalysed rearrangement of 1-arylazetidin-2-ones (1980)

A variety of 1-arylazetidin-2-ones were treated with trifluoroacetic acid under reflux, methanesulphonic acid at 100 °C, or conc. sulphuric acid to give the corresponding 2,3-dihydro-4(1H)-quinolones via acyl migration and N–CO fission. In the case of 1-(3-substituted phenyl)azetidin-2-ones, two positional isomeric products, 5- and 7-substituted 2,3-dihydro-4(1H)-quinolones were obtained. 4-Methyl-, 4-ethoxycarbonyl-, and 4-piperidin-2yl-1-arylazetidin-2-ones and their analogues were also converted into the corresponding 2-substituted 2,3dihydro-4(1H)-quinolones under acidic conditions. The 3-substituted 1-phenylazetidin-2-ones (36) and (37) were converted into the furo[3,2-c]quinoline systems (38) and (40), respectively, by application of this method.