gebhart/patrepeval huggingface dataset:
Inhibition of urokinase by 4-substituted benzo[b]thiophene-2-carboxamidines: an important new class of selective synthetic urokinase inhibitor. (1993)

Urokinase-type plasminogen activator (uPA) is an important mediator of cellular invasiveness. Specifically, cell surface receptor-bound uPA activates plasminogen to the potent general protease plasmin, which then degrades extracellular matrix or basement membrane either directly or via proteolytic activation of latent collagenases. Thus, cell surface uPA initiates an extracellular proteolytic cascade with which invasive cells eliminate barriers to movement. Since cellular invasiveness plays important roles in several disease states, including cancer metastasis and invasion, arthritis and inflammation, and diabetic retinal neovascularization, the development of synthetic uPA inhibitors is an attractive therapeutic goal. Here we show that 4-substituted benzo[b]thiophene-2-carboxamidines represent an important new class of potent and selective synthetic uPA inhibitor. Two compounds in this class, B428 and B623, inhibit human uPA in plasminogen-linked assays with median inhibition concentration (IC50) values of 0.32 and 0.07 microM, respectively. This level of inhibition represents 20- and 100-fold increases in potency, respectively, relative to the 6-7 microM potencies reported for amiloride and 4-chlorophenylguanidine, the two most potent selective synthetic uPA inhibitors previously described. Importantly, both compounds show > 300-fold selectivity for uPA relative to tissue-type plasminogen activator and > 1000-fold selectivity relative to plasmin. Lineweaver-Burk analyses show uPA inhibition by B428 and B623 to be competitive in nature with inhibition constants (Ki) of 0.53 and 0.16 microM, respectively. Since it is cell surface uPA and not free or secreted uPA that is primarily responsible for cellular invasiveness, biologically effective uPA inhibitors must be capable of inhibiting cell surface uPA. B428 and B623 meet this criterion by inhibiting cell surface uPA on HT1080 human fibrosarcoma cells with IC50 values of 0.54 and 0.20 microM, respectively. Moreover, degradation of [3H]fibronectin by HT1080 cells via cell surface uPA-mediated, plasminogen-dependent mechanisms is inhibited by B428 and B623, with IC50 values of 1.5 and 0.39 microM, respectively. In summary, 4-substituted benzo[b]thiophene-2-carboxamidines such as B428 and B623 represent the most potent class of competitive synthetic uPA inhibitors currently known. Their ability to selectively inhibit both free and cell surface uPA as well as cell surface uPA-mediated cellular degradative functions suggests that this class of compounds may hold significant promise for further development as antiinvasiveness drugs.
T helper cell‐independent neutralizing B cell response against vesicular stomatitis virus: Role of antigen patterns in B cell induction? (1995)

The neutralizing antibody response against vesicular stomatitis virus (VSV) was studied to analyze conditions necessary for induction of mature B cells. The glycoprotein of VSV (VSV-G) is expressed as repetitive epitopes that are in a rigid densely packed paracristalline form in the virus envelope; in contrast, VSV-G is present in a mobile randomly ordered form on infected cells and in micelles. We found that the rigid, paracristalline form of VSV-G spaced about 5-10 mm on VSV virons induced potent primary and secondary neutralizing B cell responses which were independent of T helper cells, whereas the more randomly distributed, mobile forms of VSV-G induced primary and secondary B cell responses that were more tightly controlled by T helper cells. These data suggest that (i) cross-linking is a critical signal for B cell activation and antibody production, and that this signal alone does not necessarily anergize or delete mature B cells, (ii) the more regularly and rigidly ordered in a distance of 5-10 nm repetitive identical antigenic determinants are, the less are primary and secondary B cell responses controlled by T cells. We therefore propose that B cells take antigen organization as a marker for foreigness.
Economic and clinical burden of opioid-induced nausea and vomiting (2016)

Opioids are the standard of care for treating moderate-to-severe pain; however, their efficacy can be limited by adverse events (AEs), including nausea and vomiting. Opioid-induced nausea and vomiting (OINV) is an inherent adverse effect of opioid treatment, exerting effects centrally and peripherally. Opioid-related AEs can impact treatment adherence and discontinuation, which can result in inadequate pain management. OINV may persist long-term, negatively affecting patient functional outcomes, physical and mental health, patient satisfaction, and overall costs of treatment. Multiple factors may contribute to OINV, including activation of opioid receptors in the chemoreceptor trigger zone, vestibular apparatus, and gastrointestinal tract. Prophylactic or early treatment with antiemetics may be appropriate for patients who are at high risk for OINV.
A Comparison of the Kubelka-Munk, Rozenberg, and Pitts-Giovanelli Methods of Analysis of Diffuse Reflectance for Several Model Systems (1983)

Previous studies have shown that the Rozenberg and Pitts-Giovanelli methods are useful alternatives that may be applied to diffusely reflecting samples that fail to conform to the Kubelka-Munk theory. These studies are extended in the present work to include samples of three additional types, namely, those which incorporate the absorber in solid solution within the scattering particles, those in which the absorber is adsorbed on the surface of the scattering particles, and those consisting of a dye spotted on chromatographic papers. No single method of analysis is superior in all cases. Although the Pitts-Giovanelli method gives a much better fit in some cases, it fails to converge in others. For this reason the Kubelka-Munk and Rozenberg methods are preferred, particularly when applied to diffusers in a medium of refractive index n = 1. For such systems the Rozenberg equation reduces to a simple form that is as easy to apply as the Kubelka-Munk equation.
[Design of next generation antibody drug conjugates]. (2013)

Chemotherapy remains one of the major tools, along with surgery, radiotherapy, and more recently targeted therapy, in the war against cancer. There have appeared a plethora of highly potent cytotoxic drugs but the poor discriminability between cancerous and healthy cells of these agents limits their broader application in clinical settings. Therapeutic antibodies have emerged as an important class of biological anticancer agents, thanks to their ability in specific binding to tumor-associated antigens. While this important class of biologics can be used as single agents for the treatment of cancer through antibody-dependent cell cytotoxicity (ADCC), their therapeutical efficacy is often limited. Antitumor antibody drug conjugates (ADCs) combine the target-specificity of monoclonal antibody (mAb) and the highly active cell-killing drugs, taking advantages of the best characteristics out of both components. Thus, insufficiency of most naked mAbs in cancer therapy has been circumvented by arming the immunoglobulin with cytotoxic drugs. Here mAbs are used as vehicles to transport potent payloads to tumor cells. ADCs contain three main components: antibody, linker and cytotoxics (also frequently referred as payload). Antibodies can recognize and specifically bind to the tumor-specific antigens, leading to an antibody-assisted internalization, and payload release. While ADC has demonstrated tremendous success, a number of practical challenges limit the broader applications of this new class of anticancer therapy, including inefficient cellular uptake, low cytotoxicity, and off-target effects. This review article aims to cover recent advances in optimizing linkers with increased stability in circulation while allowing efficient payload release within tumor cells. We also attempt to provide some practical strategies in resolving the current challenges in this attractive research area, particularly to those new to the field.
90. Identification of an Adeno-Associated Virus Binding Epitope for AVB Sepharose Affinity Resin (2015)

Antibody-based affinity chromatography is increasingly becoming an important technology in clinical AAV vector production due to the one-step removal of the large majority of host cell contaminants and simplification of downstream processes. The affinity resin AVB Sepharose (GE) is widely used in AAV purification but has a major drawback in that it does not bind all serotypes of AAV equally well. Here we report the identification of an epitope, SPAKFA, of adeno-associated virus 3B (AAV3B) which specifically mediates binding to AVB Sepharose resin. Substitution of AAV3B SPAKFA for the corresponding peptide in two poorly-binding AAV serotypes, AAV8 and rh.64R1, resulted in greatly increased affinity to AVB sepharose. In addition, the capacity of AVB Sepharose for the AAV9 serotype, which binds extremely poorly in the context of the naturally occurring epitope, could be augmented substantially upon replacement with SPAKFA. Importantly, the substitution of the AAV3B SPAKFA peptide did not affect the potency of the serotypes tested in an in vitro assay. The sequence analysis -resin binding combination approach used here to identify the SPAKFA peptide may prove to be a powerful resin selection tool for novel AAV serotypes. In addition, our discovery suggests the possibility of vector engineering to yield a universal method for the purification of multiple AAV serotypes.
Bioengineered human vascular networks transplanted into secondary mice reconnect with the host vasculature and re-establish perfusion (2011)

The ability to form anastomoses with the host circulation is essential for vascular networks incorporated within cell-seeded bioengineered tissues. Here, we tested whether and how rapidly human endothelial colony forming cell (ECFC)/mesenchymal progenitor cell (MPC)-derived bioengineered vessels, originally perfused in one mouse, could become reperfused in a secondary mouse. Using in vivo labeling with a systemically injected mixture of human- and murine-specific lectins, we demonstrate that ECFC/MPC blood vessels reconnect and are perfused at day 3 after transplantation. Furthermore, we quantified the longitudinal change in perfusion volume in the same implants before and after transplantation using contrast-enhanced micro-ultrasonic imaging. Perfusion was restored at day 3 after transplantation and increased with time, suggesting an important new feature of ECFC/MPC blood vessels: the bioengineered vessels can reconnect with the vasculature when transplanted to a new site. This feature extends the potential applications of this postnatal progenitor cell-based technology for transplantable large tissue-engineered constructs.
Pattern recognition in the automatic inspection of flaws in polymeric insulators (2005)

In this paper we report the results for radiographic pattern recognition in the automatic inspection of polymeric insulators of electric power distribution lines. Radiographic images were obtained with a tomographic industrial system from four different angles. For the segmentation of the Region of Interest (ROI) we used high gradient pixels and for segmentation of the hypothetical flaws morphological operations and extend-minima transform were used. A database with 13 features of the 714 segmented regions was obtained for the training of the neural network. After human visual inspection, it was verified in the images that out of these regions 60 were real flaws and 654 regular structures. The algorithms used for the pattern recognition showed satisfactory results for the detection of the flaws in the X-ray images of the components. Consequently, the obtained results provide encouragement for the implementation of an automatic inspection system in production lines of these components.
Probing the Specificity of the Serine Proteases Subtilisin Carlsberg and α-Chymotrypsin with Enantiomeric 1-Acetamido Boronic Acids. An Unexpected Reversal of the Normal “l”-Stereoselectivity Preference (1996)

Enantiomeric 1-acetamido boronic acids, which are N-acetyl transition state analog inhibitor analogs of l- and d-forms of the amino acids alanine, phenylalanine, p-fluorophenylalanine, p-chlorophenylalanine, and 1-naphthylalanine, have been evaluated as inhibitors of the serine proteases subtilisin Carlsberg (SC) and α-chymotrypsin (CT). All of the boronic acids are powerful competitive inhibitors of both enzymes, with, as expected, the l-enantiomers being generally more potent than the d-enantiomers. However, a dramatic reversal of the normal stereoselectivity preference was observed in the inhibition of CT by [1-acetamido-2-(1-naphthyl)ethyl]boronic acid, with the d-enantiomer becoming a 25-fold more potent inhibitor than the l-enantiomer. Furthermore, the KI of 127 nM for CT inhibition by this d-enantiomer is the lowest of any of the boronic acids evaluated. Molecular modeling analyses of the possible binding modes of the inhibitors suggest that the stereoselectivity reversal is due to S1-pocket orientations of naphthyl groups that are different from those of the aromatic side chains of the phenylalanine analogs.
Serodiagnostic Comparison between Two Methods, ELISA and Surface Plasmon Resonance for the Detection of Antibodies of Classical Swine Fever (2006)

A protein chip based on surface plasmon resonance (SPR) was developed to measure the antibody (Ab) titers of classical swine fever virus (CSFV) using the recombinant gp55 protein as an antigen. The diagnostic potential of this SPR assay for detecting the Ab titers to CSFV gp55 was compared that of the enzyme-linked immunosorbent assay (ELISA) using 170 serum samples from 14 pig farms. The SPR assay was highly specific and sensitive, and there were no cross-reactions detected. There was a strong positive correlation between the SPR and ELISA titers (n=170, r=0.869, p<0.01). Therefore, the SPR label-free method is a valuable tool in the serodiagnosis of CSFV infection and determining Ab titers after vaccination.
MEMS in RF Filter Applications: Thin‐film Bulk Acoustic Wave Technology (2003)

Abstract RF‐MEMS filters will replace conventional filters in mobile communication as they offer better performance at lower cost. Requirements and key performance parameters for filters in next‐generation mobile applications are reviewed in detail. The fundamentals of RF‐MEMS filters — and in particular thin‐film bulk acoustic wave (BAW) filters — are summarized in a comprehensive form. The state‐of‐the‐art in BAW filters and future trends are presented. Supplementary information covers manufacturing and commercialization issues.
Mammalian achaete-scute homolog 1 is transiently expressed by spatially restricted subsets of early neuroepithelial and neural crest cells. (1991)

Using monoclonal antibodies, we have examined the expression pattern of MASH1, a basic helix-loop-helix protein that is a mammalian homolog of the Drosophila achaete-scute proteins. In Drosophila, achaete-scute genes are required for the determination of a subset of neurons. In the rat embryo, MASH1 expression is confined to subpopulations of neural precursor cells. The induction of MASH1 precedes, but is extinguished upon, overt neuronal differentiation. MASH1 is expressed in the forebrain by spatially restricted domains of neuroepithelium and in the peripheral nervous system exclusively by precursors of sympathetic and enteric neurons. The features of early and transient expression, in spatially restricted subpopulations of neural precursors, are similar to those observed for achaete-scute. Thus, the amino acid sequence conservation between MASH1 and achaete-scute is reflected in a parallel conservation of cell type specificity of expression, similar to the case of mammalian MyoD and Drosophila nautilus. These data support the idea that helix-loop-helix proteins may represent an evolutionarily conserved family of cell-type determination genes, of which MASH1 is the first neural-specific member identified in vertebrates.
The c-K-ras gene and human cancer (review). (1987)

A significant number of human tumors from diverse histological origins contain c-K-ras oncogenes which have been activated by somatic point mutations resulting in single amino acids substitutions in the encoded p21 ras protein. In addition to these qualitative changes, other genetic alterations leading to increased expression of the c-K-ras gene, especially its mutated form, appear to be important in the activation of its oncogenic potential. These findings support the hypothesis that c-K-ras oncogenes are contributing in a dominant but dose dependent manner to the multistage process of human tumorigenesis. Activated c-K-ras oncogenes have been detected in human tumors at different stages of progression, including premalignant neoplasms. These studies provide evidence for the involvement of somatic mutational activation of this ras gene in the early stages of tumor development in some types of human cancer. We discuss here the structural and functional features of the human c-K-ras gene and the involvement of its activated form in human cancer.
Fundamentals of Wetting and Spreading (2012)

This chapter contains sections titled: Introduction The Concept of the Contact Angle Adhesion Tension Work of Adhesion Wa Work of Cohesion Calculation of Surface Tension and Contact Angle The Spreading of Liquids on Surfaces Contact Angle Hysteresis References
Three-Dimensional H-Bonded Networks Based on Mono- and Tetranuclear Metal-Pteridine Complexes (1996)

Abstract The crystal structure of the transition metal-pteridine complexes having three-dimensional hydrogen-bonded (H-bonded) network and stacking interactions between pteridine ligands are described; (1) Mononuclear copper(II)-pteridine complex and (2) Tetranuclear palladium(II)-pteridine complex.
Isolation and purification of a major allergen from Parietaria officinalis pollen (1987)

A major allergen of Parietaria officinalis, a species responsible for a large number of respiratory allergies in Mediterranean areas, has been identified and characterized. This allergen (Pol) was found in the fraction which precipitates between 70 and 100% ammonium sulphate saturation. Pol showed a molecular weight of 15,000 daltons as determined by SDS-PAGE and HPLC. The pI of Pol was in the pH region 4-6, IEF showing four major bands. Two major bands were shown by CIE, CRIE and immunoblotting; major contaminants or aggregates were also revealed by the latter technique and by HPLC. Pol showed an allergic specific activity 2 times higher than the crude extract; moreover it was shown to be a major allergen since it inhibited 29 out of 30 sera from allergic patients sensitive to P. officinalis.
DNA Profiling Using Solid-State Nanopores: Detection of DNA-Binding Molecules (2009)

We present a novel single-molecule method for rapidly evaluating small-molecule binding to individual DNA molecules using nanopores fabricated in ultrathin silicon membranes. A measurable shift in the residual ion current through a approximately 3.5 nm pore results from threading of a dye-intercalated DNA molecule, as compared to the typical residual current of native DNA. The average level of the residual current can be used to directly quantify the fraction of bound molecules to DNA, providing a new way to determine binding isotherms. Spatial sensitivity is also demonstrated by designing a two-segment DNA molecule that contains small-molecule binding sites in one of its two segments. Translocations of such molecules exhibit two current levels upon incubation with a DNA-binding dye, caused by selectively bound dye in one of the DNA segments. Our results, as shown here with four different dyes, coincide well with bulk fluorescence measurements performed under identical conditions. The nanopore approach for "reading-out" molecular binding along a DNA molecule, combined with the miniscule amounts of DNA required and the potential for scalability using nanopore arrays, provide a novel platform for future applications in analytical drug screening.
Comparative Study on Collagen-Binding Enzyme-Linked Immunosorbent Assay and Ristocetin Cofactor Activity Assays for Detection of Functional Activity of von Willebrand Factor (2002)

For more than two decades, the ristocetin cofactor (RCo) assay, which measures the von Willebrand factor (vWF)-mediated agglutination of platelets in the presence of the antibiotic ristocetin, has been the most common method for measuring the functional activity of vWF. There is, however, general agreement among clinical analysts that this method has major practical disadvantages in performance and reproducibility. Today, collagen-binding assays (CBA) based on the enzyme-linked immunosorbent assay (ELISA) technique that measure the interaction of vWF and collagen are an alternative analytic procedure based on a more physiological function than that of the RCo procedure. We used both assay systems in a comparative study to assess the functional activity of vWF in plasma as well as in therapeutic preparations. We measured RCo activities of plasma from healthy donors and patients with different types of von Willebrand disease (vWD) and of vWF as a drug substance in factor (F) VIII/vWF concentrates using both the aggregometric and the macroscopic methods. In addition, we measured collagen-binding activity (vWF:CB) using a recently developed commercially available CBA system. To investigate the relation between the structure and the functional activity of vWF, we isolated vWF species with different numbers of multimers from FVIII/vWF concentrates by affinity chromatography on immobilized heparin. The vWF:RCo and vWF:CB of the different fractions were measured, and the multimeric structure of vWF was analyzed by sodium dodecyl sulfate (SDS) agarose gel electrophoresis. (vWF:CB and vWF:RCo are part of the nomenclature proposed by the International Society on Thrombosis and Hemostasis Scientific and Standardization Committee [ISTH SSC] subcommittee on von Willebrand factor, in Maastricht, Germany, June 16, 2000.) Measurement of functional vWF activity by CBA can be carried out with substantially higher interassay reproducibility than can measurement of RCo. Both assay systems can be used for diagnosis and subtyping of vWD, but CBA is more sensitive than either of the two RCo methods. The analysis of vWF multimers in the different fractions obtained by affinity chromatography on heparin Sepharose showed that the activity measured both with RCo assay and CBA correlated with the degree of multimerization. Our results suggest that measurement of the functional activity of vWF by the RCo procedure can be replaced by the more reliable CBA, reflecting the physiological hemostatic activity of vWF. The CBA method appears not only to be more sensitive and easier to carry out than the RCo method is but also to have a higher reproducibility and allow better standardization.