515 research outputs found
Jacobi's last multiplier and the complete symmetry group of the Ermakov-Pinney equation
No full textThe Ermakov-Pinney equation possesses three Lie point symmetries with the algebra sl(2, R). This algebra does not provide a representation of the complete symmetry group of the Ermakov-Pinney equation. We show how the representation of the group can be obtained with the use of the method described in Nucci, J. Nonlin. Math. Phys. 12 ( 2005) ( this issue), which is based on the properties of Jacobi's last multiplier (Bianchi L, Lezioni sulla teoria dei gruppi continui finiti di trasformazioni, Enrico Spoerri, Pisa, 1918), the method of reduction of order ( Nucci, J. Math. Phys 37 ( 1996), 1772 - 1775) and an interactive code for calculating symmetries ( Nucci, Interactive REDUCE programs for calcuating classical, non-classical and Lie-Backlund symmetries for differential equations (preprint: Georgia Institute of Technology, Math 062090-051, 1990, and CRC Handbook of Lie Group Analysis of Differential Equations. Vol. 3: New Trends in Theoretical Developments and Computational Methods, Editor: Ibragimov N H, CRC Press, Boca Raton, 1996, 415 - 481)
Small-Molecule Inhibitors of Cathepsin L as Potential Anti-Metastatic Agents.
No full textThe cathepsin family of cysteine proteases is overexpressed in a variety of cancer cell lines. Cathepsin L, one such protease, is secreted into the extracellular space and plays a critical role in degrading the extracellular matrix, and facilitating the metastasis of cancer cells from a primary tumor body to a secondary site. The Pinney and Trawick Research laboratories (Baylor University) have engaged in the design, synthesis, and biological evaluation of a variety of small-molecule inhibitors of cathepsin L for potential use as anti-metastatic agents. Two such compounds, KGP94 and KGP244, have shown significant potency as inhibitors of cathepsin L, and these results along with related biological studies have advanced these compounds as promising anti-metastatic agents. A number of novel small-molecule analogues were synthesized that incorporate the benzophenone and benzoylbenzophenone backbones inherent to these two lead compounds in an ongoing effort to expand the library of compounds that could potentially interact with the cathepsin L active site
Small-Molecule Inhibitors of Cathepsin L as Potential Anti-Metastatic Agents
No full textThe cathepsin family of cysteine proteases is overexpressed in a variety of cancer cell lines. Cathepsin L, one such protease, is secreted into the extracellular space and plays a critical role in degrading the extracellular matrix, and facilitating the metastasis of cancer cells from a primary tumor body to a secondary site. The Pinney and Trawick Research laboratories (Baylor University) have engaged in the design, synthesis, and biological evaluation of a variety of small-molecule inhibitors of cathepsin L for potential use as anti-metastatic agents. Two such compounds, KGP94 and KGP244, have shown significant potency as inhibitors of cathepsin L, and these results along with related biological studies have advanced these compounds as promising anti-metastatic
agents. A number of novel small-molecule analogues were synthesized that incorporate the benzophenone and benzoylbenzophenone backbones inherent to these two lead compounds in an ongoing effort to expand the library of compounds that could potentially interact with the cathepsin L active site
Design and Synthesis of Functionalized Thiosemicarbazone Analogues as Potential Anti-metastatic Agents
No full textMetastasis is often the ultimate cause of death among cancer patients. An emerging target in the treatment of metastasis is cathepsin L which facilitates the degradation of the extracellular matrix thereby providing a pathway for the movement of cancer cells to secondary locations in the body from the primary tumor. A variety of potent small-molecule cathepsin L inhibitors bearing the thiosemicarbazone moiety have been discovered through the collaboration of the Pinney Research Group and Trawick Research Group at Baylor University. A compound known as KGP94 is among the more potent inhibitors discovered and has been re-synthesized for further studies. The majority of thiosemicarbazone containing inhibitors of cathepsin L are asymmetrical and prone to isomerization about the imine bond of the thiosemicarbazone functional group. Since isomerization may interfere with the ability of these compounds to inhibit cathespin L, a series of symmetrical thiosemicarbazone analogues was prepared and evaluated as inhibitors of cathepsin L
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
Christopher Pinney, Camera Indica. The Social Life of Indian Photographs
No full textOn doit à David MacDougall d’avoir attiré le regard des anthropologues sur le terrain exceptionnel que constituent en Inde, du point de vue d’une sociologie des identités en formation, les pratiques quotidiennes de la photographie. C’est l’« écologie complexe et changeante de la photographie » dans l’Inde coloniale et postcoloniale que Christopher Pinney a choisi d’explorer dans Camera Indica, prolongeant ainsi les travaux classiques de Barthes et de Bourdieu sur ses usages sociaux. L’auteur ..
The Design and Synthesis of Small-Molecule Anticancer Agents Targeted Through Antibody-Drug Conjugates.
No full textA relatively recent addition to the arsenal of potential treatments for cancer involves the use of vascular disrupting agents (VDAs). Small-molecule VDAs target the blood supply of a tumor, starving it of nutrients and oxygen, leading to central tumor necrosis. The Pinney Group (Baylor University) has recently synthesized a variety of unique anticancer agents that function with dual modality; as potent VDAs, and as profoundly cytotoxic anti-proliferative agents. Like many cancer treatments, at a sufficiently high concentration VDAs affect healthy cells as well as malignant cells. In an effort to efficiently target these agents, such as KGP18, towards tumors and the tumor microenvironment, they are being incorporated as payloads into appropriate antibody-drug conjugates (ADCs). These constructs feature a short amino acid sequence for further selectivity along with a self-immolative spacer. The design and synthesis of these linker constructs are presented here. Future studies will determine the efficacy of these ADCs
Systemic amyloidosis in England: an epidemiological study.
No full textEpidemiological studies of systemic amyloidosis are scarce and the burden of disease in England has not previously been estimated. In 1999, the National Health Service commissioned the National Amyloidosis Centre (NAC) to provide a national clinical service for all patients with amyloidosis. Data for all individuals referred to the NAC is held on a comprehensive central database, and these were compared with English death certificate data for amyloidosis from 2000 to 2008, obtained from the Office of National Statistics. Amyloidosis was stated on death certificates of 2543 individuals, representing 0·58/1000 recorded deaths. During the same period, 1143 amyloidosis patients followed at the NAC died, 903 (79%) of whom had amyloidosis recorded on their death certificates. The estimated minimum incidence of systemic amyloidosis in the English population in 2008, based on new referrals to the NAC, was 0·4/100 000 population. The incidence peaked at age 60-79 years. Systemic AL amyloidosis was the most common type with an estimated minimum incidence of 0·3/100 000 population. Although there are various limitations to this study, the available data suggest the incidence of systemic amyloidosis in England exceeds 0·8/100 000 of the population
Letter from the Secretary of the Treasury, transmitting an estimate from the Attorney-General of appropriation to pay W. L. Pinney for services as stenographer in the trial of certain Apache Indians in Arizona
No full text50-2AppropriationsAccount of W. Pinney. [2645] Court stenographer in case involving Apaches; 1888; Arizona.1888-39
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