124,958 research outputs found
Pinney
No full textJAS. A. Pinney, Main Street, Boise City, Idaho. B/W illustration of brick storefront; 'Books and Stationary' sign
Pinney 1
No full textPinney Bookstore, 724 W. Main Street; b/w illustration of storefront, w/ 'City Book Store' and 'Post Office' signs
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Investigation of combretastatin, dihydronaphthalene, benzosuberene, and quinoline-based analogues as inhibitors of tubulin polymerization with potential to function as vascular isrupting gents, and selected compounds as water-soluble prodrug salts and drug-linker conjugates
No full textDifferences from normal and tumor vasculature directed to the concept of discovery of vascular disrupting agents (VDAs), which interfere with oxygen and nutrients supply for tumor, as potential therapeutic agents for cancer chemotherapy. Inspired by the natural products colchicine, combretastatin A1 (CA1) and combretastatin A4 (CA4), the Pinney Group (Baylor University) has developed a variety of potent VDAs, which function as inhibitors of tubulin polymerization, such as combretastatin (KGP06 and KGP08), dihydronaphthalene (KGP05 and OXi6196), benzosuberene (KGP18 and KGP156), benzo[b]thiophene, and indole-based (OXi6196 and OXi6197) analogues. In an effort to extend the structure-activity relationship studies of VDAs bound in the colchicine binding site and using selected Pinney Group VDAs as models, several combretastatin, benzosuberene, dihydronaphthalene, and quinoline-based derivatives were designed and synthesized.
For the purpose of improving water solubility and potential bioavailability, synthetic modifications to amino acid prodrug conjugates (AAPCs) of amino variant of the Pinney Group VDAs including KGP05, KGP06, KGP08, and KGP156 were also achieved and afforded both glycinamide and serinamide prodrugs of each parent VDA. These AAPCs were evaluated for their cytotoxicity against selected cancer lines, ability to inhibit tubulin polymerization and colchicine binding, and cleavability by the enzyme leucine aminopeptidase (LAP) to generate parent compound. In addition, both KGP08 and the water-soluble glycinamide hydrochloride salt of KGP05 displayed greater than 95% decrease in bioluminescence (compared to saline control) in a tumor bearing (MDA-MB-231-luc) SCID mouse model 2 and 4 h (respectively) post treatment with administeration of moderate dosage.
Antibody-drug conjugates (ADCs) served as novel agents for cancer treatment by combining monoclonal antibody (mAb) with potent anticancer agent, thus taking advantage of specific characteristics of each component. KGP18 and KGP156 were used for the studies of design and synthesis of drug-linker conjugates by using linker payload of FDA-approved ADC (Adcetris®) as template. Ultimately, not only was KGP18 successfully incorporated into the dipeptide linker payload by chemical reactions via initiation of activating KGP18 using para-nitrophenyl chloroformate and utilizing self-immolative spacer N,N'-dimethylenediamine (DMED), but also KGP156 was fruitfully connected with the dipeptide linker payload by synthetic modifications which is beneficial from first formation of isocyanate intermediate using triphosgene
Yielding of a model glass former:An interpretation with an effective system of icosahedra
Get PDFWe consider the yielding under simple shear of a binary Lennard-Jones glass former whose super-Arrhenius dynamics are correlated with the formation of icosahedral structures. We recast this glass former as an effective system of icosahedra [Pinney, J. Chem. Phys. 143, 244507 (2015)JCPSA60021-960610.1063/1.4938424]. Looking at the small-strain region of sheared simulations, we observe that shear rates affect the shear localization behavior particularly at temperatures below the glass transition as defined with a fit to the Vogel-Fulcher-Tamman equation. At higher temperature, shear localization starts immediately on shearing for all shear rates. At lower temperatures, faster shear rates can result in a delayed start in shear localization, which begins close to the yield stress. Building from a previous work which considered steady-state shear [Pinney, J. Chem. Phys. 143, 244507 (2015)JCPSA60021-960610.1063/1.4938424], we interpret the response to shear and the shear localization in terms of a local effective temperature with our system of icosahedra. We find that the effective temperatures of the regions undergoing shear localization increase significantly with increasing strain (before reaching a steady-state plateau).</p
The development of prodrug strategies for the targeted delivery of dihydronaphthalene and benzosuberene inhibitors of tubulin polymerization.
No full textThe abnormalities present in tumor vasculature provide a promising opportunity for targeted therapeutic approaches. Vascular disrupting agents (VDAs) damage the existing tumor vasculature limiting the delivery of oxygen and nutrients to the tumor and thus inducing necrosis. Inspired by the natural products colchicine and combretastatin A-4/A1(CA4 and CA1), the Pinney Research Group in close collaboration with the Trawick Research Group has assembled a library of structurally diverse inhibitors of tubulin polymerization. In particular, dihydronaphthalene (KGP03, KGP05) and benzosuberene (KGP18, KGP156) were discovered to be potent inhibitors of tubulin polymerization that exhibited nanomolar to picomolar cytotoxicity. To extend structure activity relationship studies of VDAs that bind to the colchicine binding site on tubulin, several structurally diverse chalcones and related analogues were synthesized. Antibody-drug conjugates (ADCs) represent a promising form of targeted therapy in cancer treatment. In this strategy a potent anticancer agent is conjugated to an antibody that is specific for an antigen that is highly expressed on the surface of cancer cells. Drug linker constructs for ADC applications were synthesized containing potent benzosuberene and dihydronaphthalene inhibitors of tubulin polymerization as payloads. A variety of synthetic strategies were developed to incorporate these small-molecule VDAs (as payloads) in drug-linker constructs containing a cathepsin B cleavable linker widely used in ADC research. Tumor hypoxia presents another opportunity for targeted therapies. Bioreductively activatable prodrug constructs (BAPCs) utilize reductase enzyme mediated cleavage to convert an inactive prodrug to its active parent form in areas of pronounced hypoxia in the tumor microenvironment. Lead small-molecule inhibitors of tubulin polymerization KGP18, KGP03, and OXi8006 were incorporated into a series of potential BAPCs containing bioreductive aryl triggers. These prodrugs were evaluated as BAPCs through close collaboration with the Trawick Research Group. Cathepsin L is a protease that is upregulated in many cancers and has been implicated in cancer metastasis. The Pinney and Trawick research groups have developed a series of thiosemicarbazone inhibitors of cathepsin L. Progress towards drug-linker conjugates that feature KGP18 conjugated through self-immolative linkers to a known inhibitor of cathepsin L are reported. Additionally, dipeptides incorporating features of known inhibitors of cathepsin L were explored for selectivity
The development of prodrug strategies for the targeted delivery of dihydronaphthalene and benzosuberene inhibitors of tubulin polymerization.
No full textThe abnormalities present in tumor vasculature provide a promising opportunity for targeted therapeutic approaches. Vascular disrupting agents (VDAs) damage the existing tumor vasculature limiting the delivery of oxygen and nutrients to the tumor and thus inducing necrosis. Inspired by the natural products colchicine and combretastatin A-4/A1(CA4 and CA1), the Pinney Research Group in close collaboration with the Trawick Research Group has assembled a library of structurally diverse inhibitors of tubulin polymerization. In particular, dihydronaphthalene (KGP03, KGP05) and benzosuberene (KGP18, KGP156) were discovered to be potent inhibitors of tubulin polymerization that exhibited nanomolar to picomolar cytotoxicity. To extend structure activity relationship studies of VDAs that bind to the colchicine binding site on tubulin, several structurally diverse chalcones and related analogues were synthesized. Antibody-drug conjugates (ADCs) represent a promising form of targeted therapy in cancer treatment. In this strategy a potent anticancer agent is conjugated to an antibody that is specific for an antigen that is highly expressed on the surface of cancer cells. Drug linker constructs for ADC applications were synthesized containing potent benzosuberene and dihydronaphthalene inhibitors of tubulin polymerization as payloads. A variety of synthetic strategies were developed to incorporate these small-molecule VDAs (as payloads) in drug-linker constructs containing a cathepsin B cleavable linker widely used in ADC research. Tumor hypoxia presents another opportunity for targeted therapies. Bioreductively activatable prodrug constructs (BAPCs) utilize reductase enzyme mediated cleavage to convert an inactive prodrug to its active parent form in areas of pronounced hypoxia in the tumor microenvironment. Lead small-molecule inhibitors of tubulin polymerization KGP18, KGP03, and OXi8006 were incorporated into a series of potential BAPCs containing bioreductive aryl triggers. These prodrugs were evaluated as BAPCs through close collaboration with the Trawick Research Group. Cathepsin L is a protease that is upregulated in many cancers and has been implicated in cancer metastasis. The Pinney and Trawick research groups have developed a series of thiosemicarbazone inhibitors of cathepsin L. Progress towards drug-linker conjugates that feature KGP18 conjugated through self-immolative linkers to a known inhibitor of cathepsin L are reported. Additionally, dipeptides incorporating features of known inhibitors of cathepsin L were explored for selectivity
Pragmatic Case Studies as a Source of Unity in Applied Psychology
No full textTo unify or not to unify applied psychology: that is the question. In this article we review pendulum swings in the historical efforts to answer this question—from a comprehensive, positivist, “top-down,” deductive yes between the 1930s and the early 60s, to a postmodern no since then. A rationale and proposal for a limited, “bottom-up,” inductive yes in applied psychology is then presented, employing a case-based paradigm that integrates both positivist and postmodern themes and components. This paradigm is labeled “pragmatic psychology” and, its specific use of case studies, the “Pragmatic Case Study Method” (“PCS Method”). We call for the creation of peer-reviewed journal-databases of pragmatic case studies as a foundational source of unifying applied knowledge in our discipline. As one example, the potential of the PCS Method for unifying different angles of theoretical regard is illustrated in an area of applied psychology, psychotherapy, via the case of Mrs. B. The article then turns to the broader historical and epistemological arguments for the unifying nature of the PCS Method in both applied and basic psychology.Peer reviewe
- …
