Pittsburgh, PA, United States
Pittsburgh, PA, United States

Duquesne University of the Holy Spirit is a private Catholic university in Pittsburgh, Pennsylvania, United States. Founded by members of the Congregation of the Holy Spirit, Duquesne first opened its doors as the Pittsburgh Catholic College of the Holy Ghost in October 1878 with an enrollment of 40 students and a faculty of six. In 1911, the college became the first Catholic university in Pennsylvania. It is the only Spiritan institution of higher education in the world.Duquesne has since expanded to over 10,000 graduate and undergraduate students within a self-contained 49-acre hilltop campus in Pittsburgh's Bluff neighborhood. The school maintains an associate campus in Rome and encompasses ten schools of study. The university hosts international students from more than 80 countries although most students — about 80% — are from Pennsylvania or the surrounding region. Duquesne is considered a research university with high research activity institution by the Carnegie Foundation for the Advancement of Teaching. There are more than 79,000 living alumni of the university including two cardinals and the current bishop of Pittsburgh.The Duquesne Dukes compete in NCAA Division I. Duquesne men's basketball appeared twice in national championship games in the 1950s and won the NIT championship in 1955. Wikipedia.


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The present invention provides a compound of Formula I: wherein R is H, a methyl group, an ethyl group, a n-propyl group, an iso-propyl group, or a n-butyl group; and R^(1 )is H, a 4-methyl group, a 4-OH, a 4-OMe group, a 2,3-C_(2)H_(4 )group, a; 3,4-C_(2)H_(4 )group, a 3,4-diF, a 3,4,5-triF, or a 4-OCF_(3); and optionally including a salt or a hydrate of said compound, and further provides a pharmaceutical composition comprising the compound of Formula I and one or more acceptable pharmaceutical carriers. A method of treating a patient having cancer comprising administering a therapeutically effective amount of a compound of Formula I, or a pharmaceutical composition comprising a compound of Formula I and one or more acceptable pharmaceutical carriers to the patient is disclosed.


The present invention relates to 4-amino, 4-oxy, 4-thio or 4-alkyl substituted pyrrolo[3,2d]pyrimidines, furo[3,2d]pyrimidines, cyclopenta[d]pyridines, pyrrolo[2,3d]pyrimidines and furo[2,3d]pyrimidines, pharmaceutically acceptable salts, solvates and hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, such as for example P-glycoprotein inhibition and antitumor activity, and which inhibit paclitaxel sensitive and resistant tumor cells. Also disclosed are these compounds for use in a method of treating tumor cells and inhibiting mitosis of cancerous cells.


Hille R.,University of California at Riverside | Hall J.,University of California at Riverside | Basu P.,Duquesne University
Chemical Reviews | Year: 2014

A study is conducted to discuss the mononuclear molybdenum enzymes. Enzymes containing molybdenum in their active sites have been recognized with more than 50 molybdenum-containing enzymes being purified and biochemically characterized. It is well-established that all molybdenum-containing enzymes other than nitrogenase fall into three large and mutually exclusive families, as exemplified by the enzymes xanthine oxidase, sulfite oxidase, and DMSO reductase. The structures of the three canonical molybdenum centers in their oxidized Mo(VI) states are examined along with that for the pyranopterin cofactor. The active sites of members of the xanthine oxidase family ALSO have an LMoVIOS-(OH) structure with a square-pyramidal coordination geometry.


Grant
Agency: NSF | Branch: Continuing grant | Program: | Phase: Cellular Dynamics and Function | Award Amount: 213.00K | Year: 2016

In response to a changing environment, proteins are reshuffled in the cell - specific proteins are removed from the cell surface while others are selectively targeted to the surface. This protein reshuffling is referred to as protein trafficking and cells must make the correct decisions to control protein trafficking and ensure optimal cell growth and survival. The goal of this research is to understand how the cellular decisions that dictate protein trafficking are made. This multidisciplinary project pairs cell and molecular biology with powerful new computational biology approaches to define the parameters that determine how proteins are selectively relocalized in response to environmental changes. Key players in regulating these cellular decisions are a recently described, but poorly understood, family of proteins called the alpha-arrestins. Alpha-arrestins act as cellular mail carriers ensuring that proteins are delivered to the right location at the right time. In spite of their important role in protein trafficking, there remain critical, yet unanswered questions about alpha-arrestin function including: 1) how do alpha-arrestins recognize the discreet subset of proteins they regulate? and 2) what factors control when and where alpha-arrestins interact with the proteins they traffic? In other words, how do these molecular mail carriers know which letters to pick up, when to pick them up and where to deliver them? Understanding the answers to these questions is essential; defects in the trafficking decision making process have catastrophic consequences for the cell. The interdisciplinary nature of this research project ensures that trainees at all levels - including high school, undergraduate and graduate students - gain exposure to a wide-array of scientific approaches. The research objectives of this project will be integrated into an undergraduate laboratory course to ensure that undergraduate researchers get to experience the thrill of scientific discovery while learning science fundamentals. Undergraduate and high school student summer internships will also be created to allow students to contribute to advancing the boundary of knowledge in the dynamic field of protein trafficking.

The goal of the research is to define principles that govern selective protein trafficking using alpha-arrestins, an exciting new class of trafficking adaptor, as a model. The alpha-arrestins, conserved from yeast to humans and related to the well-characterized and clinically important mammalian beta-arrestins, are a recently described class of trafficking adaptor that play a critical role in selective protein trafficking. While we have yet to appreciate the breadth of alpha-arrestin function, in yeast they interact with the ubiquitin ligase Rsp5 to regulate the trafficking fate of cargo proteins. The alpha-arrestins are little studied and the experiments proposed here will define key posttranslational regulation of, and novel biological functions for, these critical regulators of protein trafficking. Specifically, this research will: 1) Define how disruption of the alpha-arrestin-Rsp5 interface impairs the ubiquitin ligase efficiency of Rsp5; 2) Determine how ubiquitination regulates alpha-arrestin-mediated trafficking and determine how Rsp5 activity is restricted to permit alpha-arrestin mono-ubiquitination; and 3) Comprehensively identify alpha-arrestin cargo proteins and define motifs that dictate alpha-arrestin-cargo interaction using a robust, new computational approach that employs evolutionary signatures to infer functional relationships. The results of this project will yield new paradigms for how trafficking adaptors are regulated, ubiquitin conjugation is restricted and selective cargo trafficking is achieved. Through the use of novel computational methods and complementary genetic and biochemical approaches, this research will establish the rules that govern trafficking adaptor function. Trafficking adaptors dictate cargo localization in all eukaryotes, thus the decision-making rules identified from these experiments will provide vital information to researchers with diverse interests.


The present invention provides tricyclic compounds having cytostatic and cytotoxic activity in a single molecule having receptor tyrosine kinase(s), dihydrofolate reductase, thymidylate synthase and/or dihydroorotate dehydrogenase inhibitory activity, which are useful as anti-angiogenic and anti-tumor agents. Also provided are methods of utilizing these inhibitors to treat tumor cells and other proliferative diseases and disorders.


The present invention provides tricyclic compounds, pharmaceutically acceptable salts, prodrugs, solvates, or hydrates thereof, having antimitotic activity, anti-multidrug resistance activity, for example P-glycoprotein inhibition, and antitumor activity, and which inhibit paclitaxel sensitive and resistant tumor cells. Also provided are methods of utilizing these compounds for treating tumor cells and inhibiting mitosis of cancerous cells.


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: SOLID STATE & MATERIALS CHEMIS | Award Amount: 445.00K | Year: 2016

Non-Technical Abstract
Nonlinear optical (NLO) crystals are used to shift the coherent, monochromatic light of lasers to other desirable wavelengths. Infrared nonlinear optical applications include, stand-off detection of drugs and explosives, non-invasive medical diagnosis and monitoring by breath analysis using molecular spectroscopy and infrared counter-measure systems used to defend military aircraft, just to name a few. However, the current commercially available crystals for use in infrared nonlinear optical devices suffer from drawbacks and are lacking in critical areas that limit their practical applications. The discovery of new infrared nonlinear optical materials enables the realization of new applications impacting medical, industrial and military sectors. Furthermore, the synthesis of improved infrared nonlinear optical materials allows for more reliable, longer-lasting devices having greater impact in areas where these materials have already found utility. Better understanding the relationship between the structure of the crystal and its resulting properties allows for faster progress in this field. Through this project, structure-property correlations are evolving from systematic studies of quaternary diamond-like semiconductors that combine strategic experimentation with theory, in which the ability to reliably predict properties is fostered by experimental results. These structure-property relationships are being revealed by the research efforts of postdoctoral fellows, graduate students, undergraduate researchers, high school science teachers and high school students on the research team. X-ray powder diffraction workshops organized through this project are training the next-generation workforce to solve complex scientific problems with the use of advanced research tools. Outreach activities geared toward women, minorities and economically disadvantaged students are taking place through the research groups participation in the ACS Project SEED program and interactions with local undergraduate women in STEM fields.


Technical Abstract
Current commercially available infrared nonlinear optical crystals have shortcomings, such as a lack of power-handling ability and multiphoton absorption effects that preclude usage with high-powered lasers and operation at certain wavelengths, respectively. This project, supported by the Solid State and Materials Chemistry program, focuses on the synthesis and characterization of quaternary diamond-like semiconductors and the assessment of their potential as new infrared nonlinear optical materials. Nonlinear optical (NLO) properties on powdered diamond-like semiconductor samples and additional properties of centimeter-sized single crystals are being assessed. The powdered/microcrystalline compound samples are prepared by high-temperature solid-state or lithium polysulfide flux synthesis. Second-order nonlinear optical susceptibility, laser damage threshold and the onset wavelength for phase matchability, as well as transparency range and bandgap are being measured. The preparation of centimeter-scale single crystals of selected compounds identified as promising candidates is being carried out via the vertical Bridgman method and iodine-vapor transport reactions. Certain properties of technological importance, including thermal conductivity and extreme optical transparency measured by laser calorimetry, are being assessed using these sizeable single crystals. Relationships between the composition, crystal structure and electronic structure of the materials, especially bandgap, and the observed physical properties are being considered to build crystal-chemical concepts that allow for knowledge-based optimization of materials NLO properties.


Pyrrolo[2,3-d]pyrimidine derivatives, and pharmaceutical acceptable salts thereof, useful in therapeutically treating patients with cancer are disclosed. These compounds selectively target folate receptors (FR) of cancerous tumor cells and inhibit purine synthesis and hence, DNA synthesis.


The present invention provides a compound of Formula I, and salts thereof, and a pharmaceutical composition comprising a compound of Formula I: wherein R_(1 )is selected from the group consisting of and R_(2 )is an alkyl group having from one to ten carbon atoms, orwherein R_(2 )is selected from the group consisting of R_(1 )is an alkyl group having from one to ten carbon atoms; and R is H, or an alkyl group having from one to ten carbon atoms, and R_(3 )is H, an alkyl group having from one to ten carbon atoms, or a halogen. Preferably the compound of Formula V includes wherein R_(3 )is a halogen, and most preferably wherein the halogen is chlorine. Methods of treating a patient with cancer with these compounds are also provided.


Fused cyclic pyrimidine compounds, including tautomers thereof, and pharmaceutically acceptable salts, prodrugs, solvates and hydrates thereof, are disclosed. These compounds are useful in methods for treating cancer, selectively targeting cancerous cells via the proton coupled folate transporter, folate receptor alpha, and/or folate receptor beta pathways, inhibiting GARFTase in cancerous cells, and selectively targeting activated macrophages in a patient having an autoimmune disease, such as rheumatoid arthritis.

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