Digital Commons Network^™

Pde5 Inhibitors Enhance Celecoxib Killing In Multiple Tumor Types, Laurence Booth, Jane L. Roberts, Nichola Cruickshanks, Seyedmehrad Tavallai, Timothy Webb, Peter Samuel, Adam Conley, Brittany Binion, Harold F. Young, Andrew Poklepovic, Sarah Spiegel, Paul Dent

Biochemistry and Molecular Biology Publications

The present studies determined whether clinically relevant phosphodiesterase 5 (PDE5) inhibitors interacted with a clinically relevant NSAID, celecoxib, to kill tumor cells. Celecoxib and PDE5 inhibitors interacted in a greater than additive fashion to kill multiple tumor cell types. Celecoxib and sildenafil killed ex vivo primary human glioma cells as well as their associated activated microglia. Knock down of PDE5 recapitulated the effects of PDE5 inhibitor treatment; the nitric oxide synthase inhibitor L-NAME suppressed drug combination toxicity. The effects of celecoxib were COX2 independent. Over-expression of c-FLIP-s or knock down of CD95/FADD significantly reduced killing by the drug combination. CD95 …

The Signal Transducer And Activator Of Transcription 1 (Stat1) Inhibits Mitochondrial Biogenesis In Liver And Fatty Acid Oxidation In Adipocytes, Jennifer D. Sisler, Magdalena Morgan, Vidisha Raje, Rebecca C. Grande, Marta Derecka, Jeremy Meier, Marc Cantwell, Karol Szczepanek, William J. Korzun, Edward J. Lesnefsky, Thurl E. Harris, Colleen M. Croniger, Andrew C. Larner

Biochemistry and Molecular Biology Publications

The transcription factor STAT1 plays a central role in orchestrating responses to various pathogens by activating the transcription of nuclear-encoded genes that mediate the antiviral, the antigrowth, and immune surveillance effects of interferons and other cytokines. In addition to regulating gene expression, we report that STAT1-/- mice display increased energy expenditure and paradoxically decreased release of triglycerides from white adipose tissue (WAT). Liver mitochondria from STAT1-/- mice show both defects in coupling of the electron transport chain (ETC) and increased numbers of mitochondria. Consistent with elevated numbers of mitochondria, STAT1-/- mice expressed increased amounts of PGC1α, a …

Perceived Stress Levels, Chemotherapy, Radiation Treatment And Tumor Characteristics Are Associated With A Persistent Increased Frequency Of Somatic Chromosomal Instability In Women Diagnosed With Breast Cancer: A One Year Longitudinal Study, Noran Aboalela, Debra E. Lyon, R. K. Elswick Jr., Debra Lynch Kelly, Jenni Brumelle, Harry D. Bear, Colleen Jackson-Cook

Human and Molecular Genetics Publications

While advances in therapeutic approaches have resulted in improved survival rates for women diagnosed with breast cancer, subsets of these survivors develop persistent psychoneurological symptoms (fatigue, depression/anxiety, cognitive dysfunction) that compromise their quality of life. The biological basis for these persistent symptoms is unclear, but could reflect the acquisition of soma-wide chromosomal instability following the multiple biological/psychological exposures associated with the diagnosis/treatment of breast cancer. An essential first step toward testing this hypothesis is to determine if these cancer-related exposures are indeed associated with somatic chromosomal instability frequencies. Towards this end, we longitudinally studied 71 women (ages 23-71) with early-stage …

Tumor-Specific Expression And Detection Of A Cest Reporter Gene, Il Minn, Amnon Bar-Shir, Keerthi Yarlagadda, Jeff W. M. Bulte, Paul B. Fisher, Hao Wang, Assaf A. Gilad, Martin G. Pomper

Human and Molecular Genetics Publications

Purpose

To develop an imaging tool that enables the detection of malignant tissue with enhanced specificity using the exquisite spatial resolution of MRI.

Methods

Two mammalian gene expression vectors were created for the expression of the lysine-rich protein (LRP) under the control of the cytomegalovirus (CMV) promoter and the progression elevated gene-3 promoter (PEG-3 promoter) for constitutive and tumor-specific expression of LRP, respectively. Using those vectors, stable cell lines of rat 9L glioma, 9LCMV-LRP and 9LPEG-LRP, were established and tested for CEST contrast in vitro and in vivo.

Results

9LPEG-LRP cells showed increased CEST contrast compared with 9L cells …

Tumor-Specific Expression And Detection Of A Cest Reporter Gene, Il Minn, Amnon Bar-Shir, Keerthi Yarlagadda, Jeff W. M. Bulte, Paul B. Fisher, Hao Wang, Assaf A. Gilad, Martin G. Pomper

Human and Molecular Genetics Publications

Purpose

To develop an imaging tool that enables the detection of malignant tissue with enhanced specificity using the exquisite spatial resolution of MRI.

Methods

Two mammalian gene expression vectors were created for the expression of the lysine-rich protein (LRP) under the control of the cytomegalovirus (CMV) promoter and the progression elevated gene-3 promoter (PEG-3 promoter) for constitutive and tumor-specific expression of LRP, respectively. Using those vectors, stable cell lines of rat 9L glioma, 9LCMV-LRP and 9LPEG-LRP, were established and tested for CEST contrast in vitro and in vivo.

Results

9LPEG-LRP cells showed increased CEST contrast compared with 9L cells …

Perceived Stress Levels, Chemotherapy, Radiation Treatment And Tumor Characteristics Are Associated With A Persistent Increased Frequency Of Somatic Chromosomal Instability In Women Diagnosed With Breast Cancer: A One Year Longitudinal Study, Noran Aboalela, Debra E. Lyon, R. K. Elswick Jr., Debra Lynch Kelly, Jenni Brumelle, Harry D. Bear, Colleen Jackson-Cook

Human and Molecular Genetics Publications

While advances in therapeutic approaches have resulted in improved survival rates for women diagnosed with breast cancer, subsets of these survivors develop persistent psychoneurological symptoms (fatigue, depression/anxiety, cognitive dysfunction) that compromise their quality of life. The biological basis for these persistent symptoms is unclear, but could reflect the acquisition of soma-wide chromosomal instability following the multiple biological/psychological exposures associated with the diagnosis/treatment of breast cancer. An essential first step toward testing this hypothesis is to determine if these cancer-related exposures are indeed associated with somatic chromosomal instability frequencies. Towards this end, we longitudinally studied 71 women (ages 23-71) with early-stage …

Comparison Of Effects Of P53 Null And Gain-Of-Function Mutations On Salivary Tumors In Mmtv-Hras Transgenic Mice, Dadi Jiang, Catherine I. Dumur, H. Davis Massey, Viswanathan Ramakrishnan, Mark A. Subler, Jolene J. Windle

Human and Molecular Genetics Publications

p53 is an important tumor suppressor gene which is mutated in ~50% of all human cancers. Some of these mutants appear to have acquired novel functions beyond merely losing wild-type functions. To investigate these gain-of-function effects in vivo, we generated mice of three different genotypes: MMTV-Hras/p53+/+, MMTV-Hras/p53-/-, and MMTV-Hras/p53R172H/R172H. Salivary tumors from these mice were characterized with regard to age of tumor onset, tumor growth rates, cell cycle distribution, apoptotic levels, tumor histopathology, as well as response to doxorubicin treatment. Microarray analysis was also performed to profile gene expression. The MMTV-Hras/p53-/- and …

Osteogenic Embryoid Body-Derived Material Induces Bone Formation In Vivo, Ken Sutha, Zvi Schwartz, Yun Wang, Sharon Hyzy, Barbara D. Boyan, Todd C. Mcdevitt

Biomedical Engineering Publications

The progressive loss of endogenous regenerative capacity that accompanies mammalian aging has been attributed at least in part to alterations in the extracellular matrix (ECM) composition of adult tissues. Thus, creation of a more regenerative microenvironment, analogous to embryonic morphogenesis, may be achieved via pluripotent embryonic stem cell (ESC) differentiation and derivation of devitalized materials as an alternative to decellularized adult tissues, such as demineralized bone matrix (DBM). Transplantation of devitalized ESC materials represents a novel approach to promote functional tissue regeneration and reduce the inherent batch-to-batch variability of allograft-derived materials. In this study, the osteoinductivity of embryoid body-derived material …

Reversible Strain-Induced Magnetization Switching In Fega Nanomagnets: Pathway To A Rewritable, Non-Volatile, Non-Toggle, Extremely Low Energy Straintronic Memory, Hasnain Ahmad, Jayasimha Atulasimha, Supriyo Bandyopadhyay

Electrical and Computer Engineering Publications

We report reversible strain-induced magnetization switching between two stable/metastable states in ~300 nm sized FeGa nanomagnets delineated on a piezoelectric PMN-PT substrate. Voltage of one polarity applied across the substrate generates compressive strain in a nanomagnet and switches its magnetization to one state, while voltage of the opposite polarity generates tensile strain and switches the magnetization back to the original state. The two states can encode the two binary bits, and, using the right voltage polarity, one can write either bit deterministically. This portends an ultra-energy-efficient non-volatile “non-toggle” memory.

Periodic And Chaotic Orbits Of A Discrete Rational System, N. Lazaryan, Hassan Sedaghat

Mathematics and Applied Mathematics Publications

We study a rational planar system consisting of one linear-affine and one linear-fractional difference equation. If all of the system’s parameters are positive (so that the positive quadrant is invariant and the system is continuous), then we show that the unique fixed point of the system in the positive quadrant cannot be repelling and the system does not have a snap-back repeller. By folding the system into a second-order equation, we find special cases of the system with some negative parameter values that do exhibit chaos in the sense of Li and Yorke within the positive quadrant of the plane.

Turning Over A New Leaf: Cannabinoid And Endocannabinoid Modulation Of Immune Function, Guy A. Cabral, Thomas J. Rogers, Aron H. Lichtman

Microbiology and Immunology Publications

Cannabis is a complex substance that harbors terpenoid-like compounds referred to as phytocannabinoids. The major psychoactive phytocannabinoid found in cannabis ∆9-tetrahydrocannabinol (THC) produces the majority of its pharmacological effects through two cannabinoid receptors, termed CB1 and CB2. The discovery of these receptors as linked functionally to distinct biological effects of THC, and the subsequent development of synthetic cannabinoids, precipitated discovery of the endogenous cannabinoid (or endocannabinoid) system. This system consists of the endogenous lipid ligands N- arachidonoylethanolamine (anandamide; AEA) and 2-arachidonylglycerol (2-AG), their biosynthetic and degradative enzymes, and the CB1 and CB2 receptors that they activate. Endocannabinoids have been …

Intracellular Uropathogenic E. Coli Exploits Host Rab35 For Iron Acquisition And Survival Within Urinary Bladder Cells, Neha Dikshit, Pradeep Bist, Shannon N. Fenlon, Niyas Kudukkil Pulloor, Christelle En Lin Chua, Marci A. Scidmore, Jason A. Carlyon, Bor Luen Tang, Swaine L. Chen, Bindu Sukumaran

Microbiology and Immunology Publications

Recurrent urinary tract infections (UTIs) caused by uropathogenic E. coli (UPEC) are common and morbid infections with limited therapeutic options. Previous studies have demonstrated that persistent intracellular infection of bladder epithelial cells (BEC) by UPEC contributes to recurrent UTI in mouse models of infection. However, the mechanisms employed by UPEC to survive within BEC are incompletely understood. In this study we aimed to understand the role of host vesicular trafficking proteins in the intracellular survival of UPEC. Using a cell culture model of intracellular UPEC infection, we found that the small GTPase Rab35 facilitates UPEC survival in UPEC-containing vacuoles …

Intracellular Uropathogenic E. Coli Exploits Host Rab35 For Iron Acquisition And Survival Within Urinary Bladder Cells, Neha Dikshit, Pradeep Bist, Shannon N. Fenlon, Niyas Kudukkil Pulloor, Christelle En Lin Chua, Marci A. Scidmore, Jason A. Carlyon, Bor Len Tang, Swaine L. Chen, Bindu Sukumaran

Microbiology and Immunology Publications

Recurrent urinary tract infections (UTIs) caused by uropathogenic E. coli (UPEC) are common and morbid infections with limited therapeutic options. Previous studies have demonstrated that persistent intracellular infection of bladder epithelial cells (BEC) by UPEC contributes to recurrent UTI in mouse models of infection. However, the mechanisms employed by UPEC to survive within BEC are incompletely understood. In this study we aimed to understand the role of host vesicular trafficking proteins in the intracellular survival of UPEC. Using a cell culture model of intracellular UPEC infection, we found that the small GTPase Rab35 facilitates UPEC survival in UPEC-containing vacuoles …

Orientia Tsutsugamushi Ankyrin Repeat-Containing Protein Family Members Are Type 1 Secretion System Substrates That Traffic To The Host Cell Endoplasmic Reticulum, Lauren Viebrock, Sean M. Evans, Andrea R. Beyer, Charles L. Larson, Paul A. Beare, Hong Ge, Smita Singh, Kyle G. Rodino, Robert A. Heinzen, Allen L. Richards, Jason A. Carlyon

Microbiology and Immunology Publications

Scrub typhus is an understudied, potentially fatal infection that threatens one billion persons in the Asia-Pacific region. How the causative obligate intracellular bacterium, Orientia tsutsugamushi, facilitates its intracellular survival and pathogenesis is poorly understood. Many intracellular bacterial pathogens utilize the Type 1 (T1SS) or Type 4 secretion system (T4SS) to translocate ankyrin repeat-containing proteins (Anks) that traffic to distinct subcellular locations and modulate host cell processes. The O. tsutsugamushi genome encodes one of the largest known bacterial Ank repertoires plus T1SS and T4SS components. Whether these potential virulence factors are expressed during infection, how the Anks are potentially secreted, and …

Dna Double-Strand Breaks And Telomeres Play Important Roles In Trypanosoma Brucei Antigenic Variation, Bibo Li

Biological, Geological, and Environmental Faculty Publications

Human-infecting microbial pathogens all face a serious problem of elimination by the host immune response. Antigenic variation is an effective immune evasion mechanism where the pathogen regularly switches its major surface antigen. In many cases, the major surface antigen is encoded by genes from the same gene family, and its expression is strictly monoallelic. Among pathogens that undergo antigenic variation, Trypanosoma brucei (a kinetoplastid), which causes human African trypanosomiasis, Plasmodium falciparum (an apicomplexan), which causes malaria, Pneumocystis jirovecii (a fungus), which causes pneumonia, and Borrelia burgdorferi (a bacterium), which causes Lyme disease, also express their major surface antigens from loci …

Zipline-Related Injuries Treated In Us Eds, 1997-2012, Rachel M. Billock, Jonathan J. Anderegg, Tracy J. Mehan, Thiphalak Chounthirath, Gary A. Smith

Faculty Publications - Department of Communication and Cinematic Arts

Purpose

To investigate the epidemiology of zipline-related injuries in the United States.

Basic Procedures

The National Electronic Injury Surveillance System database was used to examine non-fatal zipline-related injuries treated in US emergency departments (EDs) from 1997 through 2012. Sample weights were applied to calculate national estimates.

Main Findings

From 1997 through 2012, an estimated 16850 (95% CI, 13188-20512) zipline-related injuries were treated in US EDs. The annual injury rate per 1 million population increased by 52.3% from 7.64 (95% CI, 4.86-10.42) injuries in 2009 (the first year with a stable annual estimate) to 11.64 (95% CI, 7.83-15.45) injuries in 2012. …

Dietrich Bonhoeffer, His Life In Brief, Kerry Irish

Faculty Publications - Department of History and Politics

This brief 3500-word biography emphasizes Bonhoeffer's theology, spiritual journey, and work in the German resistance until his death in April 1945.

Review Of Shell's "Wampum And The Origins Of American Money", Paul Otto

Faculty Publications - Department of History and Politics

No abstract provided.

Religious Accommodations And The Common Good, Mark David Hall

Faculty Publications - Department of History and Politics

"Citizens, civic leaders, and jurists interested in good public policy should look to history as a guide to the impact of laws and constitutional provisions aimed at protecting religious actors. American civic leaders and jurists, at both the national and state levels, have long created significant protections for religious Americans who object to neutral, generally applicable laws. At their best, Americans have agreed that government should not force individuals to violate their sincerely held religious convictions unless it has compelling reasons for doing so. Moreover, the nation and the states have still been able to achieve important policy objectives in …

Study Guide For Dietrich Bonhoeffer's "Life Together", Kerry Irish

Faculty Publications - Department of History and Politics

"The study begins with a short essay on Bonhoeffer’s life that explains the context of his work, especially Life Together. The study guide is organized in five parts, easily read in weekly installments. There is also a short conclusion."

Connected: An Enhanced Online Interface For Engagement Between Industry And Academia, David Kirk, John J. Keogh, Terry Maguire

Conference Papers

The drive for third level education institutes to engage with industry, enterprise and the community recognises their interdependence and need for continuous knowledge exchange. The extent to which students are capable of embracing their post-qualification roles, may be determined by the currency of the curriculum and work-readiness, which is informed by the context of the ‘real-worlds’ however they are shaped. Similarly, the activities that challenge industry, enterprise and the community could find support in the broad the spectrum of knowledge, skills and expertise that resides in the domain of formal education.

A key obstacle to collaboration between higher education institutes …

Annual Reports Of The Town Officers Northwood, Nh For The Fiscal Year Ending December 31, 2014 And Of The School District For The Fiscal Year Ending June 30, 2014., Northwood Town Representatives

Northwood, NH Annual Reports

This is an annual report containing vital statistics for a town/city in the state of New Hampshire.

Annual Report Of The Officers, Trustees, Boards, Committees, And Agents For The Town Of Nottingham, New Hampshire For The Year Ending December 31, 2014., Nottingham Town Representatives

Nottingham, NH Annual Reports

This is an annual report containing vital statistics for a town/city in the state of New Hampshire.

Learning From Experience: An Introduction To The Journal Of Experiential Learning, Patricia E. Salkin

Journal of Experiential Learning

Commitment to experiential learning begins with the dean, yet this has not been the typical questioning in candidate interview processes. Important are indicators of past performance, examples of interpersonal skills, creativity, and knowledge of current challenges facing the profession, legal education and the individual school. Often over-looked, however, is what else the candidate brings to the table in terms of their approach to legal pedagogy, past experiences that may provide other important insights into what may subconsciously influence the candidate’s particular approach to one or more issues. It can be difficult to glean this from the typical thirty to forty-five …

Scalpel Please: Cutting To The Heart Of Medical Records Disputes In Employment Law Cases, Megan I. Brennan

William Mitchell Law Review

No abstract provided.

Esat-6 Targeting To Dec205+ Antigen Presenting Cells Induces Specific-T Cell Responses Against Esat-6 And Reduces Pulmonary Infection With Virulent Mycobacterium Tuberculosis, Aarón Silva-Sánchez, Selene Meza-Pérez, Adriana Flores-Langarica

Publications

Airways infection with Mycobacterium tuberculosis (Mtb) is contained mostly by T cell responses, however, Mtb has developed evasion mechanisms which affect antigen presenting cell (APC) maturation/recruitment delaying the onset of Ag-specific T cell responses. Hypothetically, bypassing the natural infection routes by delivering antigens directly to APCs may overcome the pathogen's naturally evolved evasion mechanisms, thus facilitating the induction of protective immune responses. We generated a murine monoclonal fusion antibody (α-DEC-ESAT) to deliver Early Secretory Antigen Target (ESAT)-6 directly to DEC205⁺ APCs and to assess its in vivo effects on protection associated responses (IFN-γ production, in vivo CTL killing, and …

Land-Value Taxation As A Method Of Encouraging Growth In Baltimore, Michael Safko

University of Baltimore Journal of Land and Development

The events that occurred last May have left many residents of Baltimore wondering what can be done to rebuild their city better than it was before.1 One particular suggestion is the elimination of all current property taxes along with the implementation of a land-value tax (LVT).2 An LVT would tax property owners based on the unimproved land they own, rather than on the improvements and structures that have been built on the land.3 The argument follows that this method of taxation would incentivize property owners to develop their land, rather than leave it undeveloped so they can pay less in …

17th Annual Student Academic Conference, Minnesota State University Moorhead

Student Academic Conference Abstract Books

Minnesota State University Moorhead Student Academic Conference abstract book.

Comments: Private Investment: Trojan-Horse Or Shining Knight For America's Public Housing Stock, Andrew Balashov

University of Baltimore Journal of Land and Development

The numbers are staggering. The nation's largest public housing authorities ("HA's") are in a state of crisis as a result of massive budget shortfalls. The Department of Housing and Urban Development (HUD) estimates it would take roughly $26 billion to remedy the problem. To put this in perspective, in 2014 the New York City Public Housing Authority had a $77 million deficit and $18 billion worth of "unfunded capital improvements," - a euphemism for basic upgrades to building systems such as water, heat, air conditioning, and elevators. At present, many of these systems are woefully below acceptable livability standards. This …

Edited Transcript Of Symposium On Public-Private Partnerships, "Public-Private Partnerships: A Vehicle For Economic Development And Promotion Of The Rule Of Law"

University of Baltimore Journal of Land and Development

Speakers:

Scott Walchak
Preston Bryant
Martin Jacobson
Shyamala Shukla
Patrick Decorla-Souza
Jodie Misiak
John Smolen

The University of Baltimore Journal of Land and Development hosted a symposium on Public-Private Partnerships (P3s) and their impact on economic development and the rule of law. The main topics of the symposium were what is a P3, the key elements of P3 legislation both internationally and nationally, the historical development of P3s, and with the foregoing in mind what is the role for attorneys during the lifecycle of any P3? The following is an edited transcript of symposium and the discussion that followed.