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Evanston, IL, United States

Northwestern University is a private research university with campuses in Evanston and Chicago in Illinois, United States. Home to twelve schools and colleges, Northwestern offers 124 undergraduate degrees and 145 graduate and professional degrees.Northwestern was founded in 1851 by John Evans, for whom the City of Evanston is named, and eight other lawyers, businessmen and Methodist leaders. Its founding purpose was to serve the Northwest Territory, an area that today includes the states of Ohio, Indiana, Illinois, Michigan, Wisconsin and parts of Minnesota. Instruction began in 1855; women were admitted in 1869. Today, the main campus is a 240-acre parcel in Evanston, along the shores of Lake Michigan just 12 miles north of downtown Chicago. The university's law and medical schools are located on a 25-acre campus in Chicago's Streeterville neighborhood. In 2008, the university opened a campus in Education City, Doha, Qatar with programs in journalism and communication.Consistently ranked as a major national and global university, Northwestern is classified as a leading research institution, attracting over $550 million in sponsored research each year. In addition, Northwestern has one of the largest university endowments in the United States, currently valued at $9.8 billion. In 2014, the university accepted 12.9% of undergraduate applicants, making Northwestern one of the most selective universities in the country.Northwestern is a founding member of the Big Ten Conference and remains the only private university in the conference. The Northwestern Wildcats compete in 19 intercollegiate sports in the NCAA's Division I Big Ten Conference. Wikipedia.

Blatner N.R.,Northwestern University
Science translational medicine | Year: 2012

The role of regulatory T cells (T(regs)) in human colon cancer (CC) remains controversial: high densities of tumor-infiltrating T(regs) can correlate with better or worse clinical outcomes depending on the study. In mouse models of cancer, T(regs) have been reported to suppress inflammation and protect the host, suppress T cells and protect the tumor, or even have direct cancer-promoting attributes. These different effects may result from the presence of different T(reg) subsets. We report the preferential expansion of a T(reg) subset in human CC with potent T cell-suppressive, but compromised anti-inflammatory, properties; these cells are distinguished from T(regs) present in healthy donors by their coexpression of Foxp3 and RORγt. T(regs) with similar attributes were found to be expanded in mouse models of hereditary polyposis. Indeed, ablation of the RORγt gene in Foxp3(+) cells in polyp-prone mice stabilized T(reg) anti-inflammatory functions, suppressed inflammation, improved polyp-specific immune surveillance, and severely attenuated polyposis. Ablation of interleukin-6 (IL-6), IL-23, IL-17, or tumor necrosis factor-α in polyp-prone mice reduced polyp number but not to the same extent as loss of RORγt. Surprisingly, loss of IL-17A had a dual effect: IL-17A-deficient mice had fewer polyps but continued to have RORγt(+) T(regs) and developed invasive cancer. Thus, we conclude that RORγt has a central role in determining the balance between protective and pathogenic T(regs) in CC and that T(reg) subtype regulates inflammation, potency of immune surveillance, and severity of disease outcome.

Gidalevitz T.,Northwestern University
Cold Spring Harbor perspectives in biology | Year: 2011

Organisms survive changes in the environment by altering their rates of metabolism, growth, and reproduction. At the same time, the system must ensure the stability and functionality of its macromolecules. Fluctuations in the environment are sensed by highly conserved stress responses and homeostatic mechanisms, and of these, the heat shock response (HSR) represents an essential response to acute and chronic proteotoxic damage. However, unlike the strategies employed to maintain the integrity of the genome, protection of the proteome must be tailored to accommodate the normal flux of nonnative proteins and the differences in protein composition between cells, and among individuals. Moreover, adult cells are likely to have significant differences in the rates of synthesis and clearance that are influenced by intrinsic errors in protein expression, genetic polymorphisms, and fluctuations in physiological and environmental conditions. Here, we will address how protein homeostasis (proteostasis) is achieved at the level of the cell and organism, and how the threshold of the stress response is set to detect and combat protein misfolding. For metazoans, the requirement for coordinated function and growth imposes additional constraints on the detection, signaling, and response to misfolding, and requires that the HSR is integrated into various aspects of organismal physiology, such as lifespan. This is achieved by hierarchical regulation of heat shock factor 1 (HSF1) by the metabolic state of the cell and centralized neuronal control that could allow optimal resource allocation between cells and tissues. We will examine how protein folding quality control mechanisms in individual cells may be integrated into a multicellular level of control, and further, even custom-designed to support individual variability and impose additional constraints on evolutionary adaptation.

Leonardi P.M.,Northwestern University
MIS Quarterly: Management Information Systems | Year: 2011

Employees in many contemporary organizations work with flexible routines and flexible technologies. When those employees find that they are unable to achieve their goals in the current environment, how do they decide whether they should change the composition of their routines or the materiality of the technologies with which they work? The perspective advanced in this paper suggests that the answer to this question depends on how human and material agencies-the basic building blocks common to both routines and technologies-are imbricated. Imbrication of human and material agencies creates infrastructure in the form of routines and technologies that people use to carry out their work. Routine or technological infrastructure used at any given moment is the result of previous imbrications of human and material agencies. People draw on this infrastructure to construct a perception that a technology either constrains their ability to achieve their goals, or that the technology affords the possibility of achieving new goals. The case of a computer simulation technology for automotive design used to illustrate this framework suggests that perceptions of constraint lead people to change their technologies while perceptions of affordance lead people to change their routines. This imbrication metaphor is used to suggest how a human agency approach to technology can usefully incorporate notions of material agency into its explanations of organizational change.

Muller W.A.,Northwestern University
Annual Review of Pathology: Mechanisms of Disease | Year: 2011

Neither the innate nor adaptive immune system "responds" unless leukocytes cross blood vessels. This process occurs through diapedesis, in which the leukocyte moves in an ameboid fashion through tightly apposed endothelial borders and, in some cases, through the endothelial cell itself. This review focuses on the active role of the endothelial cell in diapedesis. Several mechanisms play a critical role in transendothelial migration, including signals derived from clustering of apically disposed intercellular adhesion molecule 1 and vascular cell adhesion molecule 1, disruption or loosening of adherens junctions, and targeted recycling of platelet/endothelial cell adhesion molecule and other molecules from the recently described lateral border recycling compartment. Surprisingly, many of the same molecules and mechanisms that regulate paracellular migration also control transcellular migration. A hypothesis that integrates the various known mechanisms of transmigration is proposed. Copyright © 2011 by Annual Reviews. All rights reserved.

Rinella M.E.,Northwestern University
JAMA - Journal of the American Medical Association | Year: 2015

IMPORTANCE: Nonalcoholic fatty liver disease and its subtype nonalcoholic steatohepatitis affect approximately 30% and 5%, respectively, of the US population. In patients with nonalcoholic steatohepatitis, half of deaths are due to cardiovascular disease and malignancy, yet awareness of this remains low. Cirrhosis, the third leading cause of death in patients with nonalcoholic fatty liver disease, is predicted to become the most common indication for liver transplantation. OBJECTIVES: To illustrate how to identify patients with nonalcoholic fatty liver disease at greatest risk of nonalcoholic steatohepatitis and cirrhosis; to discuss the role and limitations of current diagnostics and liver biopsy to diagnose nonalcoholic steatohepatitis; and to provide an outline for the management of patients across the spectrum of nonalcoholic fatty liver disease. EVIDENCE REVIEW: PubMed was queried for published articles through February 28, 2015, using the search terms NAFLD and cirrhosis, mortality, biomarkers, and treatment. A total of 88 references were selected, including 16 randomized clinical trials, 44 cohort or case-control studies, 6 population-based studies, and 7 meta-analyses. FINDINGS: Sixty-six percent of patients older than 50 years with diabetes or obesity are thought to have nonalcoholic steatohepatitis with advanced fibrosis. Even though the ability to identify the nonalcoholic steatohepatitis subtype within those with nonalcoholic fatty liver disease still requires liver biopsy, biomarkers to detect advanced fibrosis are increasingly reliable. Lifestyle modification is the foundation of treatment for patients with nonalcoholic steatosis. Available treatments with proven benefit include vitamin E, pioglitazone, and obeticholic acid; however, the effect size is modest (<50%) and none is approved by the US Food and Drug Administration. The association between nonalcoholic steatohepatitis and cardiovascular disease is clear, though causality remains to be proven in well-controlled prospective studies. The incidence of nonalcoholic fatty liver disease-related hepatocellular carcinoma is increasing and up to 50% of cases may occur in the absence of cirrhosis. CONCLUSIONS AND RELEVANCE: Between 75 million and 100 million individuals in the United States are estimated to have nonalcoholic fatty liver disease and its potential morbidity extends beyond the liver. It is important that primary care physicians, endocrinologists, and other specialists be aware of the scope and long-term effects of the disease. Early identification of patients with nonalcoholic steatohepatitis may help improve patient outcomes through treatment intervention, including transplantation for those with decompensated cirrhosis. © 2015 American Medical Association. All rights reserved.

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