Search results for "DOP"
showing 10 items of 4870 documents
Development of Novel Benzodiazepine-Based Peptidomimetics as Inhibitors of Rhodesain from Trypanosoma brucei rhodesiense.
2020
Starting from the reversible rhodesain inhibitors 1 a-c, which have Ki values towards the target protease in the low-micromolar range, we have designed a series of peptidomimetics, 2 a-g, that contain a benzodiazepine scaffold as a β-turn mimetic; they are characterized by a specific peptide sequence for the inhibition of rhodesain. Considering that irreversible inhibition is strongly desirable in the case of a parasitic target, a vinyl ester moiety acting as Michael-acceptor was introduced as the warhead; this portion was functionalized in order to evaluate the size of corresponding enzyme pocket that could accommodate this substituent. With this investigation, we identified an irreversibl…
Synthesis and biological evaluation of papain-family cathepsin L-like cysteine protease inhibitors containing a 1,4-benzodiazepine scaffold as antipr…
2014
Novel papain-family cathepsin L-like cysteine protease inhibitors endowed with antitrypanosomal and antimalarial activity were developed, through an optimization study of previously developed inhibitors. In the present work, we studied the structure-activity relationships of these derivatives, with the aim to develop new analogues with a simplified and more synthetically accessible structure and with improved antiparasitic activity. The structure of the model compounds was significantly simplified by modifying or even eliminating the side chain appended at the C3 atom of the benzodiazepine scaffold. In addition, a simple methylene spacer of appropriate length was inserted between the benzod…
p53 Isoform D133p53a: A Novel Transcriptional Enhancer of T-Cell Effector Function to Improve T-Cell Based Cancer Immunotherapy
2018
Abstract Background: Adoptive transfer of genetically modified T lymphocytes with tumor antigen-specific receptor has proven efficacy in cancer immunotherapy. However, in many patients the overall benefit is still limited due to various tumor escape mechanisms. Cell damage and metabolic/hypoxic stress in the tumor microenvironment (TME) can lead to a dysfunctional anti-tumor T cell response called T cell senescence. The tumor suppressor TP53 is a master molecule in the regulation of cell cycle and senescence. Few studies have demonstrated the critical role of p53 isoforms in the regulation of cellular senescence mainly in tumor cells. However, their role in tumor infiltrating lymphocytes (T…
The tumor suppressor CYLD controls the function of murine regulatory T cells.
2012
Abstract CYLD was originally identified as a tumor suppressor gene mutated in familial cylindromatosis, an autosomal dominant predisposition to multiple benign neoplasms of the skin known as cylindromas. The CYLD protein is a deubiquitinating enzyme that acts as a negative regulator of NF-κB and JNK signaling through its interaction with NEMO and TNFR-associated factor 2. We have previously described a novel mouse strain that expresses solely and excessively a naturally occurring splice variant of CYLD (CYLDex7/8). In this study, we demonstrate that CYLD plays a critical role in Treg development and function. T cells of CYLDex7/8 mice had a hyperactive phenotype manifested by increased prod…
Naturally occurring short splice variant of CYLD positively regulates dendritic cell function
2009
Abstract Deubiquitination of NF-κB members by CYLD is crucial in controlling the magnitude and nature of cell activation. The role of the naturally occurring CYLD splice variant in dendritic cell (DC) function was analyzed using CYLDex7/8 mice, which lack the full-length CYLD (flCYLD) transcript and overexpress the short splice variant (sCYLD). Bone marrow–derived DCs from CYLDex7/8 mice display a hyperactive phenotype in vitro and in vivo and have a defect in establishing tolerance with the use of DEC-205–mediated antigen targeting to resting DCs. The combination of sCYLD overexpression and lack of flCYLD in CYLDex7/8 DCs leads to enhanced NF-κB activity accompanied by an increased nuclear…
Analysing longitudinal turbulence intensity in vegetated channels
2007
Vegetation altering hydrodynamic conditions of an open channel flow controls the exchanges of sediment, nutrients and contaminants. In this paper the turbulence structure of open-channel flow over a flexible grass vegetation is investigated. Velocity measurements were carried out, in a rectangular flume, using a 2D-ADV (Acoustic Doppler Velocimeter) for different values of stem concentration, water discharge, and bed slope. The experimental results showed that: 1) the maximum value of the longitudinal turbulence intensity occurs at a water depth close to the bent vegetation height; 2) the turbulence intensity damps for increasing values of the stem concentration; 3) above the vegetation hei…
A cultural comparison study of smartphone adoption in Uzbekistan, South Korea and Turkey
2017
Smartphone popularity is increasing due to the technological advances that mean manufacturers can make more sophisticated devices, and telecommunication companies can provide better connections. Gartner reported that 403 million smartphones were sold in the fourth quarter of 2015, a 9.7% increase over the same period in 2014. It is a common perception that users tend to utilise advanced technology to increase productivity. However, there are studies indicating quite opposite or alternatively slow rates of adoption. To avoid this, companies invest in studying consumer behaviour. The purpose of the study is to examine the effects of drivers and cultural differences on smartphone acceptance in…
Two New Heteropodine Genera from Southern Continental Asia (Araneae: Sparassidae)
2000
Two new genera of the subfamily Heteropodinae (Araneae: Sparassidae) are described from southern continental Asia: Pseudopoda gen. nov. and Bhutaniella gen. nov. Type species are designated and described: Pseudopoda prompta (OP-Cambridge 1885) COMB. NOV. and Bhutaniella hillyardi sp. nov. The following species, originally described as Heteropoda spp., are included in Pseudopoda gen. nov.: P. casaria (Simon 1897) COMB. NOV., P. exigua (Fox 1938) COMB. NOV., P. exiguoides (Song & Zhu 1999) COMB. NOV., P. grahami (Fox 1936) COMB. NOV., P. lushanensis (Wang 1990) COMB. NOV., P. virgata (Fox 1936) COMB. NOV., P. zhangmuensis (Hu & Li 1983) COMB. NOV., P. zhejiangensis (Zhang & Kim 1996) COMB. NO…
Oxidation of carbidopa by tyrosinase and its effect on murine melanoma
2009
Oxidation of the anti-Parkinsonian agent carbidopa by tyrosinase was investigated. The products of this reaction were identified as 3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid and 6,7-dihydroxy-3-methylcinnoline. These results demonstrate that after oxidation of the catechol moiety to an o-quinone either a redox exchange with the hydrazine group or a cyclization reaction occur. The cyclization product underwent additional oxidation reactions leading to aromatization. The cyclization reaction is undesired in the case of hydrazine-containing anti-melanoma prodrugs and will have to be taken into account in designing such compounds. Carbidopa was tested against B16(F10) melanoma cells in cul…
Difusión de innovaciones y redes sociales en la agricultura. Análisis de tendencias en la Comunidad Valenciana y Reino Unido
2023
Esta tesis doctoral se estructura en torno a tres temas principales de estudio. El primer tema (Artículo 1) se centra en el análisis bibliométrico de la difusión de innovaciones en la agricultura. El objetivo es obtener una comprensión integral de las tendencias de investigación en esta área, proporcionando una base sólida para aplicaciones prácticas. El segundo tema (Artículos 2, 4 y 5) gira en torno al análisis de los procesos de adopción y difusión de innovaciones en la agricultura sostenible. Esto incluye dos estudios realizados en la Comunidad Valenciana (Artículos 2 y 5) y otro estudio realizado en el Reino Unido (Artículo 4). Los objetivos de este tema son dobles. En primer lugar, an…