Kinetic limitations of cooperativity based drug delivery systems

We study theoretically a novel drug delivery system that utilizes the overexpression of certain proteins in cancerous cells for cell specific chemotherapy. The system consists of dendrimers conjugated with "keys" (ex: folic acid) which "key-lock" bind to particular cell membrane proteins (ex: folate receptor). The increased concentration of "locks" on the surface leads to a longer residence time for the dendrimer and greater incorporation into the cell. Cooperative binding of the nanocomplexes leads to an enhancement of cell specificity. However, both our theory and detailed analysis of in-vitro experiments indicate that the degree of cooperativity is kinetically limited. We demonstrate that cooperativity and hence the specificity to particular cell type can be increased by making the strength of individual bonds weaker, and suggest a particular implementation of this idea. The implications of the work for optimizing the design of drug delivery vehicles are discussed.Comment: 4 pages, 4 figures, v3: minor revision

Using Archaeological Methods in Cemetery Surveys with Emphasis on the Application of Lidar

Cemeteries are important components of history. Surveying cemeteries is a good way to not only keep track of the information that cemeteries contain, but it also can provide a professional, systematic and standardized way of recording information and presenting it to the public. The preservation of cemeteries through recording information from the gravestones remains an important task that needs to be undertaken. Preservation, in this context, refers to having a comprehensive record of the gravestone data and maps of the gravestone locations to aid those who seek to garner information from the cemetery as well as preventing the loss of this crucial information to a disaster, all without damage to the cemetery or the gravestones. This study was conducted for the purpose of determining the most comprehensive method of gathering gravestone data and mapping cemeteries with consideration to cost effectiveness, time efficiency, data accuracy and quantity of data. For the purpose of this study three specific types of technology were used to gather gravestone data and map each cemetery. These technologies included a handheld Global Positioning System (GPS), a total station, and Light Detection and Ranging (LiDAR) technology. In order to determine the effectiveness of using LiDAR, surveys were conducted in two cemeteries in the Southeastern United States -- Ebenezer Lutheran Cemetery in Ebenezer, Georgia which has an earliest recorded burial of 1813 and a cemetery located on Mont Repose plantation in Coosawhatchie, South Carolina which has an earliest recorded burial of 1885. As a result, for the purposes of this study, the LiDAR scan was not the most effective as far as cost, time and quantity of data. It is a good additional resource to use in a cemetery survey, and a comparative analysis of information obtained by all the survey methods supports this result. In conclusion, while LiDAR is a new and effective tool in the archaeologist\u27s toolbox. Like any technology it has constraints. While it may prove to be useful, it should be used in conjunction with other methods to produce the best results

The effect of liposomes’ surface electric potential on the uptake of hematoporphyrin

AbstractHematoporphyrin is being used as a photosensitizer in photodynamic therapy of tumors, as well as of other clinical cases. Many classes of tetrapyrroles, including hematoporphyrin, are partitioning quite easily into the external cytoplasmic membrane as the mechanism of cellular uptake. Several chemical and physical parameters of the membrane were studied for their effect on the extent of porphyrins' partitioning. In this manuscript we report, for the first time, a quantitative analysis of the effect of the membrane's surface electric potential on the partitioning. We prepared liposomes, as membrane models, composed on zwitterionic DMPC lipid, as well as DMPC liposomes that contain a small, varying fraction of negatively charged DMPS and positively charged DOTAP. We found that indeed the surface potential had a very strong effect on the binding constant of HP, which is negatively charged at the physiological pH that was used. The trend in the apparent binding constant can be formulated and fitted with the Gouy-Chapman model of surface potential. We found that the average concentration of HP within the aqueous shell that has a thickness of the Debye layer around the liposome is determining the extent of binding in the law of mass action

HABITANTES DE GUETOS DE TODOS OS PAÍSES: UNI-VOS! VOCÊS NÃO TÊM NADA A PERDER, A NÃO SER OS MUROS!

O presente artigo apresenta uma discussão com o texto de Loïc Wacquant Que é um gueto? Construindo um conceito sociológico, particularmente a respeito das relações entre o conceito wacquantiano de hipergueto e o mais tradicional de gueto. A autora particularmente argumenta que, ao contrário do que se pensa, as condições extremas de exclusão social a que estão submetidas as populações habitantes dos atuais hiperguetos não as torna mais frágeis socialmente: historicamente se sabe que essas são condições propícias para a mobilização social, a que se soma um fator emergente nos últimos anos, capaz de mobilizar com sucesso populações oprimidas: o Islamismo. RESIDENTS OF THE GHETTOS OF ALL COUNTRIES: UNITE! YOU HAVE NOTHING TO LOSE BUT YOUR WALLS! Abstract This article discusses Loic Wacquants paper, What is a ghetto? Building a sociological concept, with a particular focus on on Wacquants concept of hyperghetto and its relation to the more traditional concept of ghetto. The author makes the argument that, contrary to what is commonly assumed, the extreme conditions of social exclusion that the inhabitants of todays hyperghettos are subjected to does not make them more socially fragile: historically we can se that these conditions propitiate social mobilization. Another emergent factor of recent years can be added to the scenario, showing considerable ability in the succesful mobilization of oppressed populations: Islam. HABITANTS DE GHETTOS DE TOUS LES PAYS: UNISSEZ-VOUS! VOUS NAVEZ RIEN A PERDRE, SI CE NEST VOS MURS ! Résumé Cet article établit un dialogue avec le texte de Loïc Wacquant «Quest-ce que le ghetto?». En bâtissant un concept sociologique, particulièrement en ce qui concerne les relations entre le concept wacquantien «dhyperghetto» et le concept traditionnel de «ghetto», lauteur argumente qu à lopposé de la pensée générale, les conditions extrêmes dexclusion sociale auxquelles sont soumises les populations habitant les hyperghettos actuels ne les rendent pas plus fragiles socialement : historiquement on sait que ces conditions sont favorables à la mobilisation sociale, à laquelle sajoute un élément de plus ces dernières années, capable de mobiliser avec succès les populations opprimées : lIslamisme

Origin of broad polydispersion in functionalized dendrimers and its effects on cancer cell binding affinity

Nanoparticles with multiple ligands have been proposed for use in nanomedicine. The multiple targeting ligands on each nanoparticle can bind to several locations on a cell surface facilitating both drug targeting and uptake. Experiments show that the distribution of conjugated ligands is unexpectedly broad, and the desorption rate appears to depends exponentially upon the mean number of attached ligands. These two findings are explained with a model in which ligands conjugate to the nanoparticle with a positive cooperativity of $\approx 4kT$, and that nanoparticles bound to a surface by multiple bonds are permanently affixed. This drives new analysis of the data, which confirms that there is only one time constant for desorption, that of a nanoparticle bound to the surface by a single bond.Comment: 4 pages, with 6 figure

Dendrimer-Entrapped Gold Nanoparticles as a Platform for Cancer-Cell Targeting and Imaging

We present a general approach for the targeting and imaging of cancer cells using dendrimer-entrapped gold nanoparticles (Au DENPs). Au DENPs were found to be able to covalently link with targeting and imaging ligands for subsequent cancer-cell targeting and imaging. The Au DENPs linked with defined numbers of folic acid (FA) and fluorescein isothiocyanate (FI) molecules are water soluble, stable, and biocompatible. In 14vitro studies show that the FA- and FI-modified Au DENPs can specifically bind to KB cells (a human epithelial carcinoma cell line) that overexpress high-affinity folate receptors and they are internalized dominantly into lysosomes of target cells within 2 14h. These findings demonstrate that Au DENPs may serve as a general platform for cancer imaging and therapeutics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56102/1/1245_ftp.pd

Promotion of innovative products in Siberia through information technologies

The article raised the question of the promotion of innovative products and services on the territory of Siberia. The topic today is very urgent, because most of these products come to Russia with the Western countries. In view of the prevailing negative trends, it becomes a matter of efficient import substitution, production of which can not be built without a market analysis, creating and promoting innovation in the aftermath of the goods on the market

Heterocyclic scaffolds as promising anticancer agents against tumours of the central nervous system: Exploring the scope of indole and carbazole derivatives

Tumours of the central nervous system are intrinsically more dangerous than tumours at other sites, and in particular, brain tumours are responsible for 3% of cancer deaths in the UK. Despite this, research into new therapies only receives 1% of national cancer research spend. The most common chemotherapies are temozolomide, procarbazine, carmustine, lomustine and vincristine, but because of the rapid development of chemoresistance, these drugs alone simply aren’t sufficient for long-term treatment. Such poor prognosis of brain tumour patients prompted us to research new treatments for malignant glioma, and in doing so, it became apparent that aromatic heterocycles play an important part, especially the indole, carbazole and indolocarbazole scaffolds. This review highlights compounds in development for the treatment of tumours of the central nervous system which are structurally based on the indole, carbazole and indolocarbazole scaffolds, under the expectation that it will highlight new avenues for research for the development of new compounds to treat these devastating neoplasms

Dendrimer-Functionalized Shell-crosslinked Iron Oxide Nanoparticles for In-Vivo Magnetic Resonance Imaging of Tumors

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58645/1/1671_ftp.pd