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Papadopoulou M.V.,NorthShore University HealthSystem | Bloomer W.D.,NorthShore University HealthSystem | Lepesheva G.I.,Vanderbilt University | Rosenzweig H.S.,Oakton Community College | And 7 more authors.
Journal of Medicinal Chemistry | Year: 2015

3-Nitro-1H-1,2,4-triazole-based amides with a linear, rigid core and 3-nitrotriazole-based fluconazole analogues were synthesized as dual functioning antitrypanosomal agents. Such compounds are excellent substrates for type I nitroreductase (NTR) located in the mitochondrion of trypanosomatids and, at the same time, act as inhibitors of the sterol 14α-demethylase (T. cruzi CYP51) enzyme. Because combination treatments against parasites are often superior to monotherapy, we believe that this emerging class of bifunctional compounds may introduce a new generation of antitrypanosomal drugs. In the present work, the synthesis and in vitro and in vivo evaluation of such compounds is discussed. © 2015 American Chemical Society.


Papadopoulou M.V.,NorthShore University HealthSystem | Bloomer W.D.,NorthShore University HealthSystem | Rosenzweig H.S.,Oakton Community College | Arena A.,San Diego State University | And 3 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2014

Twenty-three 3-nitrotriazole-based and 2-nitroimidazole-based amides and sulfonamides were screened for antitubercular (anti- TB) activity in aerobic Mycobacterium tuberculosis H37Rv by using the BacTiter-Glo (BTG) microbial cell viability assay. In general, 3-nitrotriazole-based sulfonamides demonstrated anti-TB activity, whereas 3-nitrotriazole-based amides and 2-nitroimidazole- based amides and sulfonamides were inactive. Three 3-nitrotriazole-based sulfonamides (compounds 4, 2, and 7) demonstrated 50% inhibitory concentration (IC50), IC90, and MIC values of 0.38, 0.43, and 1.56 M(compound 4), 0.57, 0.98, and 3.13 μM(compound 2), and 0.79, 0.87, and 3.13 μM(compound 7), respectively. For 3-nitrotriazole-based sulfonamides, anti-TB activity increased with lipophilicity, whereas the one-electron reduction potential (E1/2) did not play a role. 2-Nitroimidazole- based analogs, which were inactive in the BTG assay, were significantly more active in the low-oxygen assay and more active than the 3-nitrotriazoles. All active nitrotriazoles in the BTG assay were similarly active or more potent (lower MIC values) against resistant strains, with the exception of compounds 2, 3, 4, and 8, which demonstrated greater MIC values against isoniazid- resistant strains. Five 3-nitrotriazole-based sulfonamides demonstrated activity in infected murine J774 macrophages, causing log reductions similar to those seen with rifampin. However, some compounds caused toxicity in uninfected macrophages. In conclusion, the classes of 3-nitrotriazole-based amides and sulfonamides merit further investigation as potential antitubercular agents. © 2014, American Society for Microbiology. All Rights Reserved.


Papadopoulou M.V.,NorthShore University HealthSystem | Bloomer W.D.,NorthShore University HealthSystem | Rosenzweig H.S.,Oakton Community College | Kaiser M.,Swiss Tropical and Public Health Institute | And 3 more authors.
Bioorganic and Medicinal Chemistry | Year: 2013

We have previously shown that 3-nitro-1H-1,2,4-triazole-based amines demonstrate significant trypanocidal activity, in particular against Trypanosoma cruzi, the causative parasite of Chagas disease. In the present work we further expanded our research by evaluating in vitro the trypanocidal activity of nitrotriazole-based piperazines and nitrotriazole-based 2-amino-1,3- benzothiazoles to establish additional SARs. All nitrotriazole-based derivatives were active or moderately active against T. cruzi; however two of them did not fulfill the selectivity criteria. Five derivatives were active or moderately active against Trypanosoma brucei rhodesiense while one derivative was moderately active against Leishmania donovani. Active compounds against T. cruzi demonstrated selectivity indexes (toxicity to host cells/toxicity to T. cruzi amastigotes) from 117 to 1725 and 12 of 13 compounds were up to 39-fold more potent than the reference compound benznidazole. Detailed SARs are discussed. © 2013 Elsevier Ltd. All rights reserved.


Papadopoulou M.V.,NorthShore University HealthSystem | Bloomer W.D.,NorthShore University HealthSystem | Rosenzweig H.S.,Oakton Community College | Ashworth R.,Queen Mary, University of London | And 5 more authors.
Future Medicinal Chemistry | Year: 2013

Background: Chagas disease is caused by the parasite Trypanosoma cruzi, is endemic in Latin America and leads to an estimated 14,000 deaths per year and around 100 million people at risk of infection. Drugs currently used in the treatment of Chagas are old, partially effective and have numerous side effects. Methodology: We have previously reported that 3-nitro-1H-1,2,4-triazole-based compounds demonstrate significant and selective activity against T. cruzi amastigotes in infected L6 cells via activation of a type I nitroreductase, specific to trypanosomatids. In the present work we evaluated in vivo 13 of these compounds based on their high in vitro potency against T. cruzi (IC 50 < 1 μM) and selectivity (SI: toxicity to L6 cells/toxicity against T. cruzi amastigotes > 200). Representative compounds of different chemical classes were included. A fast luminescence assay with transgenic parasites that express luciferase, and live imaging techniques were used. A total of 11 out of 13 compounds demonstrated significant antichagasic activity when administered intraperitoneally for 5-10 days at relatively small doses. The best in vivo activity was demonstrated by amides and sulfonamide derivatives. ADMET studies were performed for specific compounds. Conclusion: At least three compounds were identified as effective, non-toxic antichagasic agents suitable for further development. © 2013 Future Science Ltd.


Filus J.K.,Oakton Community College | Filus L.Z.,Northeastern Illinois University
AIP Conference Proceedings | Year: 2010

We define and investigate stochastic dependences that occurs in some vital problems in biomedical science as well as (in parallel) in reliability. Between others, we extend the classical model for stochastic dependence discovered by Cox in 1972 and widely applied in bio-medical investigations. Our extension is rather new and relies on adding to Cox's formula an additional term depending on some, possibly different than those in the original Cox formula, explanatory variables. These variables, in general, are random. Thus, the classical Cox formula becomes a special case of the model we consider. The so extended Cox pattern forms an essential general background for construction of some more specific stochastic models applied in reliability, and, first of all, in modeling a cancer-ill human's residual life time. Additionally, the extended model's analytical structure provides tools that facilitate analytical description of an additional pattern of 'parallelism' between some 'physical' phenomena and their stochastic reflections. © 2010 American Institute of Physics.


Filus J.K.,Oakton Community College | Filus L.Z.,Northeastern Illinois University
AIP Conference Proceedings | Year: 2012

Continuing the discussion on the multivariate pseudodistributions we show some possibilities for their eventual application as stochastic models for a variety of reliability and biomedical problems. With that regard we mostly concentrate on stochastic modeling "stress → life-time" dependence phenomena. For that we find the conditional densities of a human residual life-time, given an "amount of the stress". Some quantitative characterizations of the random stress are provided too. © 2012 American Institute of Physics.


Filus J.K.,Oakton Community College | Filus L.Z.,Northeastern Illinois University
AIP Conference Proceedings | Year: 2012

The classic bivariate and multivariate Gaussian probability density' pattern is recognized as a special case of the more general "parameter dependence" paradigm for the stochastic dependence between random variables. This recognition leads to formulation of new method for the construction of many other (than the normal) multivariate densities called "pseudodistributions". The latter preserve some essential properties of the Gaussian case. © 2012 American Institute of Physics.


Thakore B.K.,Northwestern University | Naffziger-Hirsch M.E.,Oakton Community College | Richardson J.L.,University of Illinois at Chicago | Williams S.N.,Northwestern University | McGee R.,Northwestern University
BMC Medical Education | Year: 2014

Background: Approaches to training biomedical scientists have created a talented research community. However, they have failed to create a professional workforce that includes many racial and ethnic minorities and women in proportion to their representation in the population or in PhD training. This is particularly true at the faculty level. Explanations for the absence of diversity in faculty ranks can be found in social science theories that reveal processes by which individuals develop identities, experiences, and skills required to be seen as legitimate within the profession. Methods/Design. Using the social science theories of Communities of Practice, Social Cognitive Career Theory, identity formation, and cultural capital, we have developed and are testing a novel coaching-based model to address some of the limitations of previous diversity approaches. This coaching intervention (The Academy for Future Science Faculty) includes annual in-person meetings of students and trained faculty Career Coaches, along with ongoing virtual coaching, group meetings and communication. The model is being tested as a randomized controlled trial with two cohorts of biomedical PhD students from across the U.S., one recruited at the start of their PhDs and one nearing completion. Stratification into the experimental and control groups, and to coaching groups within the experimental arms, achieved equal numbers of students by race, ethnicity and gender to the extent possible. A fundamental design element of the Academy is to teach and make visible the social science principles which highly influence scientific advancement, as well as acknowledging the extra challenges faced by underrepresented groups working to be seen as legitimate within the scientific communities. Discussion. The strategy being tested is based upon a novel application of the well-established principles of deploying highly skilled coaches, selected and trained for their ability to develop talents of others. This coaching model is intended to be a complement, rather than a substitute, for traditional mentoring in biomedical research training, and is being tested as such. © 2014 Thakore et al.; licensee BioMed Central Ltd.


Grant
Agency: NSF | Branch: Continuing grant | Program: | Phase: ADVANCED TECH EDUCATION PROG | Award Amount: 820.58K | Year: 2013

The project is to use remote technology in real-time to enhance nanotechnology education and training, with a goal to accelerate exposure of students in grades 10-14 to the nanotechnology field and to potential careers as nanotechnicians. The project promotes the use of remote technology and nanotechnology education in community colleges and high schools throughout Illinois by focusing on the following key activities: 1) training faculty to use lab and remote technology that permits real-time experimentation when they return to their own institutions, 2) developing and implementing new nanotechnology curriculum and labs in existing STEM courses, 3) encouraging the formation of nanotechnology 2+2 partnerships across the state, and 4) evaluating the effects of the new curriculum and labs on the outcomes of interest.

The remote technology has the potential to be transformative in bringing previously unavailable pedagogy into more classrooms. Exposure to nanotechnology at the high school and community college level encourages more students to explore the field in subsequent post-secondary education. The program design is based on proven models and involves participants in a statewide partnership that enhances collaboration and scientific inquiry. Collaboration with the Illinois Science and Technology Coalition and IL STEM Learning Exchange ensures outreach to traditionally underserved institutions and the program design makes it easily accessible to colleges and schools throughout the region.


Grant
Agency: NSF | Branch: Standard Grant | Program: | Phase: IUSE | Award Amount: 4.75K | Year: 2015

This project will build upon the infrastructure of Zooniverse.org to create authentic research experiences for introductory astronomy students. Education research indicates that including authentic research in science classes improves attitudes towards science and scientists in a diverse cross-section of students. The curriculum materials will be tested and refined at a broad spectrum of institutional settings before dissemination.

Introductory astronomy generally provides students little insight into the realities of being a scientist. This project will address this deficiency by introducing an authentic research experience for students into the astronomy for non-majors curriculum. It will utilize the classification and meta-data exploration capabilities of the Zooniverse platform. The proposed course curriculum will support students in building foundational research skills and practices through a series of in-class activities and a semester-long group research project. These activities will employ a state-of-the-art online platform to explore data collection, manipulation, and interpretation within the core topics in the curriculum. The project team will assess student learning and attitudinal gains through traditional in-class testing and conceptual questioning that is embedded within the Zooniverse online environment, as well as student interviews. This includes assessing the impact of the research experience on students understanding of the nature of science, conceptual astronomy learning gains (e.g. the Zooniverse Astronomical Concept Survey, Prather et al, 2013), and interest in pursuing a STEM major. The team will also assess the impact of different implementations of the online platform as well as the ease of implementation of the new curricular materials in a variety of institutional settings, course structures, and content focus. They will use the insight gained to develop the most effective curricular and training materials. All curricular materials, instructional guides, online Zooniverse tools, and underlying code will be widely disseminated.

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