Insights into DNA platination within unusual structural settings

2D [1H, 15N] HSQC NMR spectroscopy has been used to monitor reaction and product formation between [Pt(15NH3)2I2] and nucleic acids possessing irregular topologies and containing site specific phosphorothioate substitution in the phosphodiester backbone. Comparison of the reaction profiles of dimer nucleic acids with and without phosphorothioate substitution is made with their short nucleic acid counterparts containing the key dimer components. Whereas d(GpA) is relatively unreactive towards [Pt(15NH3)2I2], NMR evidence suggests that the tandem sheared mismatch duplex d(GCG3pAGC)2 reacts to form the head-to-tail inter-strand G3-N7-Pt-G3-N7 cross-link. The equivalent phosphorothioate R,S-d(GsA) reacts to form a mono-iodo, mono-sulphur adduct, whereas the tandem sheared mismatch phosphorothioate duplex d(GCGsAG5C)2 (VIs) reacts to form the unusual intra-strand macrochelate [Pt(15NH3)2{d(VIs-G5-N7)},S]2+ in which platinum is attached at both sulphur and G5-N7. Experimental evidence supports the formation of a stabilized mismatch duplex in which platinum is attached to two nitrogen centres in the sequence d(CGCGpTGCG) in contrast to R,S-d(CGCGsT5GCG) for which NMR evidence supports macrochelate-stabilized hairpin loop formation cross-linked at both phosphorothioate sulphur and T5-N

Manro v. Almeida: Piracy, Maritime Torts, and Attachment In Rem

In 1820, Captain Joseph Almeida, on the Bolivar and under South American colors, pursued and captured the Spanish ship Santiago off the coast of the Chesapeake Bay. On board was $5000 in specie owned by a small group of Baltimore merchants. The Baltimore merchants brought a libel against Captain Almeida and requested an attachment in rem to force Captain Almeida to answer for the maritime tort. Although the attachment initially issued, the lower court restored Captain Almeida’s goods. In 1825, the United States Supreme Court ruled that attachment in rem was a proper remedy for a maritime tort

Estimating the Economic Value of Water for Agriculture and Other Industries in Tennessee

Tennessee’s currently abundant water resources could eventually become stressed as population continues to rise, climate change impacts water resources, and as agricultural producers continue to increase irrigation. These stresses could impact the productivity of the agricultural sectors and other economic sectors as competition for limited water resources increases. Farmers, policymakers, and researchers alike could benefit from quantifying the economic value of water to help formulate cost-effective and sustainable water use practices. This analysis establishes the water withdrawals (also referred to as “water use”) per dollar of output for competing economic sectors and uses those values in an Input-Output Linear Programming (IOLP) model to maximize gross regional product to the Tennessee economy. Shadow values are also determined for each industry using the IOLP model. The accounting matrix of economic activity is from the Impact Analysis for Planning model (IMPLAN), and total water withdrawals and water withdrawal coefficients were found using a combination of data from the United States Geological Survey (USGS), the United States Department of Agriculture (USDA), and IMPLAN. The results of this model indicate that water use in the agricultural and governmental sectors have relatively low economic values while water use in the real estate, forestry inputs, and insurance sectors have high economic values. These results are observed with both the water use coefficients in Chapter 1 and the marginal contributions to gross regional product in Chapter 2

A thalamocortical mechanism for the absence of overt motor behavior in covertly aware patients:Thalamocortical Mechanism for the Absence of Overt Motor Behavior

Importance It is well accepted that a significant number of patients in a vegetative state are covertly aware and capable of following commands by modulating their neural responses in motor imagery tasks despite remaining nonresponsive behaviorally. To date, there have been few attempts to explain this dissociation between preserved covert motor behavior and absent overt motor behavior. Objectives To investigate the differential neural substrates of overt and covert motor behavior and assess the structural integrity of the underlying networks in behaviorally nonresponsive patients. Design, Setting, and Participants A case-control study was conducted at an academic center between February 7, 2012, and November 6, 2014. Data analysis was performed between March 2014 and June 2015. Participants included a convenience sample of 2 patients with severe brain injury: a paradigmatic patient who fulfilled all clinical criteria for the vegetative state but produced repeated evidence of covert awareness (patient 1) and, as a control case, a patient with similar clinical variables but capable of behavioral command following (patient 2). Fifteen volunteers participated in the study as a healthy control group. Main Outcomes and Measures We used dynamic causal modeling of functional magnetic resonance imaging to compare voluntary motor imagery and motor execution. We then used fiber tractography to assess the structural integrity of the fibers that our functional magnetic resonance imaging study revealed as essential for successful motor execution. Results The functional magnetic resonance imaging study revealed that, in contrast to mental imagery, motor execution was associated with an excitatory coupling between the thalamus and primary motor cortex (Bayesian model selection; winning model Bayes factors >17). Moreover, we detected a selective structural disruption in the fibers connecting these 2 regions in patient 1 (fractional anisotropy, 0.294; P = .047) but not in patient 2 (fractional anisotropy, 0.413; P = .35). Conclusions and Relevance These results suggest a possible biomarker for the absence of intentional movement in covertly aware patients (ie, specific damage to motor thalamocortical fibers), highlight the importance of the thalamus for the execution of intentional movements, and may provide a target for restorative therapies in behaviorally nonresponsive patients

Synergies: University-Museum Collaborations

The purpose of this report is to provide documentation of the University-Museums Synergies Initiative between a Department of Marine, Earth, and Atmospheric Sciences and a Museum of Natural Sciences. The goals of this initiative were to 1)identify specific projects and opportunities might be developed to strengthen the collaboration between institutions and 2) gain a better understanding of MEAS researchers’ and Museum employees\u27 perspectives on university-museum partnerships

Essays in the Economics of Education

This dissertation studies the reasons for and consequences of different choices in human capital investment. The theme connecting the three essays is a desire to understand reasons for inequality in educational choices and outcomes, as well as shed light on policies that may or may not remedy those inequalities. In each chapter, I use quantitative casual inference methods and rich administrative data to understand students' educational trajectories. The first chapter investigates the role of beliefs about academic performance in explaining gender differences in college major choice. I run a randomized controlled trial with undergraduate students across seven STEM disciplines. Treated students receive information about their performance relative to their classmates and to STEM majors. I find that absent intervention, men overestimate their own relative rank by more and are more likely to underestimate how other STEM majors perform, while women are more likely to overestimate others. The intervention shrinks gender gaps in biased beliefs by between a third and half. Treatment also closes the two-credit gender gap in STEM course-taking during the subsequent semester by ten percent. These changes are driven largely by low-performing, overconfident men correctly updating their beliefs and taking fewer STEM credits, rather than encouraging women to stick with STEM. The second chapter studies the effect of grading policies on college course-taking and major choice, with a focus on differences by gender. I study a natural experiment within the economics department of a large university, which changed its grading policy to give out higher grades in its introductory economics courses. I leverage this variation to compare students with the same underlying performance but who received different letter grades. I find that receiving a higher grade in introductory economics increases the likelihood that a student will take the next course in the sequence by between two and three percentage points, with much smaller effects on economics major choice. Higher economics grades lead more students to declare a major in business---the highest-earning major at the studied institution. I find little evidence that women are more responsive to grades than men. My findings suggest that grade inflation as a policy may work to retain more students within a field, but is unlikely to close gender gaps. In Chapter Three, I study the Advanced Placement (AP) program, which is nearly ubiquitous in American high schools and is often touted as a way to close achievement gaps by income and race. Using administrative data from Michigan, I exploit variation within high schools across time in AP course offerings to identify the causal effect of AP course availability on college choice and degree attainment. I find that higher income students, White and Asian students, and higher-achieving students are both more likely to take advantage of AP courses when they are offered as well as more likely to reap the benefits of taking them. The results imply that not only does the AP program fail to close achievement gaps, it may actually be harming the most disadvantaged students. I find suggestive evidence that the negative effects for low-income and underrepresented minority students are driven by negative spillovers or the diversion of resources from non-AP students and courses, rather than direct effects of these students taking AP.PHDPublic Policy & EconomicsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/169965/1/srowen_1.pd