Development of novel breast cancer-targeted spect imaging peptides by phage display

"May 2014."Dissertation Supervisor: Dr. Susan L. Deutscher.Includes vita.Malignancy of the breast is the leading cause of cancer among women and the second leading cause of cancer-related death. Despite implementation of mammograms and breast exams, there still exists a need to detect highly aggressive cancer at its earliest stage. Development of targeted molecules, such as peptides, by phage display allows for specific imaging of a targeted antigen. The hypothesis of this dissertation was that phage display could be used select novel peptides for breast cancer imaging. In vivo phage display selection is a strategy that allows for selection of peptides based on their function in the environment in which they will be used. The work here demonstrated that in vivo phage display successfully was able to select a peptide with improved pharmacokinetics and tumor targeting in comparison to a previous generation. Additionally, the selection yielded a peptide that mimicked a putative tumor vasculature. associated protein termed EGFL6. EGFL6 was determined to be expressed in breast cancer and may serve as the basis for future investigations. Finally, a peptide was discovered that bound to and imaged BT-474 human breast cancer tumors in mice. This cell line is of importance because it represents resistance susceptible breast cancer, a major cause of death among women. These results demonstrate the utility of phage display and highlight the novel targeting agents that can be obtained by the technology.Includes bibliographical references (pages 137-151)

Does Colour Filling-In Account for Colour Perception in Natural Images?

It is popular to attribute the appearance of extended colour fields to a process of filling-in from the differential colour signals at colour edges, where one colour transitions to another. We ask whether such a process can account for the appearance of extended colour fields in natural images. Some form of colour filling-in must underlie the equiluminant colour Craik-O’Brien-Cornsweet effect and the Water colour Effect, but these effects are too weak to account for the appearance of extended colour fields in natural images. Moreover, the graded colour disappearance effect reported as evidence for colour filling-in does not work under natural viewing conditions. We demonstrate that natural images do not look very colourful when their colour is restricted to edge transitions . Moreover, purely chromatic images with maximally graded (‘edgeless’) transitions look fully colourful. Consequently, we conclude that colour filling-in makes no more than a minor contribution to the appearance of extended colour regions in natural images

Heavier drinking American college students may self-select into study abroad programs: An examination of sex and ethnic differences within a high-risk group

As with other heavier drinking groups, heavier drinking American college students may self-select into study abroad programs with specific intentions to use alcohol in the foreign environment. This cross-sectional study used a sample of 2144 students (mean age = 20.00, SD = 1.47) to explore differences in alcohol use and related negative consequences among (1) students intending to study abroad while in college, (2) students not intending to study abroad, and (3) students reporting prior study abroad participation. Results revealed that participants with no intention to study abroad drank less and experienced fewer alcohol-related consequences than participants intending to study abroad. In addition, students reporting prior completion of study abroad programs drank more and reported more hazardous alcohol use than those not intending to study abroad. Ethnic and sex differences existed; with White students, males, and females intending to study abroad and non-White students who previously completed study abroad programs demonstrating the most risk. These findings provide empirical support that study abroad students may be a heavier drinking subgroup necessitating intervention prior to beginning programs abroad

Public rules about using and owning real estate in Cuba

The discussion on urban land continues to be absent in most of the specialized Cuban literature about planning and economic policies, despite its relevance. In very thorough essays about the present challenges and future development of the Cuban economy, nothing is said about the need for adequate public land policies and the implementation of public value capture mechanisms as part of the economic development of the country. The issue is complex, there is a void of almost half a century of not dealing with land value, but these reasons are not sufficient to justify the continued lack of vision in this direction, all the more when the Cuban cities are in desperate need to reverse the deterioration and stagnation that affects them. The Cuban state determines the general rules under which citizens and organisations may own and use real estate. These are rules about property rights and about the limitations - in compliance with aspects such as state security, environmental and heritage protection, economic development, social equity and human and civil rights – on exercising those rights. In doing this, the Cuban state is no different from other states: most states make such rules and enforce them when necessary. What is particular to Cuba is the content of those rules. In particular, the Cuban state has the monopoly to perform land development and management. There are public institutions to plan and deal with all of these aspects, and there are no recognised real estate markets in the country. Another important aspect is the utmost importance given to planning. But in spite of this, Cuban urban planners have rarely been certain of what will be built and where. The main reason for this may be that, despite the numerous master plans to study and anticipate development trends, most of the decisions ultimately involve top officials who envision the projects and establish the investment priorities according to the public interests or needs and the historical moment, irrespective of the plans. This article intends to give a clear picture of how things are done in the public sector, how the administration works, and under which legal framework. I will look at the physical planning system and its importance in the location and implementation of land use, investment projects and housing programs, and at the legal procedures that include licenses for construction, demolition, habitat and other licenses for heritage conservation and redevelopment. I will analyze the difficulties faced by the Cuban planning and legal system with respect to land and urban development, in the attempt to understand the limits imposed by the government on land and urban development, and I will explore to what extent those limits are to blame for the increasing irregularities and violations at all levels of the formal procedures for land and property. I will also introduce the public and personal rights concerning housing, buying and selling, permutes, donations and other tenure alternatives; and clarify the civil responsibilities, namely types of ownership, properties, property registers and so forth in order to expose the opportunities and accessibility of the system but also its limitations

Randomized Controlled Trial of BASICS for Heavy Drinking Mandated and Volunteer Undergraduates: 12-Month Outcomes

This is the first randomized trial testing whether heavy drinking undergraduates mandated to the Brief Alcohol Screening and Intervention for College Students (BASICS) program following a campus alcohol violation would benefit as much as heavy drinking volunteers up to one year post-intervention using high-risk control groups to model disciplinary-related and naturalistic changes in drinking. Participants (61% male; 51% mandated; 84% Caucasian; Mage = 20.14 years) were screened for heavy drinking and randomized to BASICS (n = 115) or control (n = 110). Outcome measures collected at baseline, 4 weeks, 3, 6, and 12 months post-intervention included the Daily Drinking Questionnaire and Rutgers Alcohol Problem Inventory. At 4 weeks post-intervention, intent-to-treat multilevel longitudinal models showed that regardless of referral group (mandated or volunteer) BASICS significantly decreased weekly drinking, typical drinks, and peak drinks relative to controls (ds = .41-.92). Decreases in alcohol problems were of large effect size (d = .87). At 12 months post-intervention, BASICS participants (regardless of referral group) reported significantly fewer alcohol problems (d = .56) compared to controls. Significant intervention gains for peak drinks and typical drinks were sustained in both referral groups relative to controls (ds = .42; .11). Referral group had no significant main effect and did not interact with intervention condition to predict outcomes. BASICS was associated with less drinking and fewer alcohol problems, even among heavier drinking mandated students up to one year post-intervention. Provision of BASICS-style programs within disciplinary settings may help reduce heavy drinking and alcohol problems among at-risk students

Group Identification as a Moderator of the Relationship Between Perceived Social Norms and Alcohol Consumption

Previous research has shown that social norms are among the strongest predictors of college student drinking. Among college students, perceiving that “others” drink heavier relative to themselves has been strongly and consistently associated with heavier drinking. Research has also shown that the more specifically “others” are defined, the stronger the association with one’s own drinking. The present research evaluated whether group identification as defined by feeling closer to specific groups moderates the associations between perceived drinking norms in the group and one’s own drinking. Participants included 3752 (61% Female) students who completed online assessments of their perceived drinking norms for four groups of students on their campus as well as identification with each group and participants’ own drinking behavior. Results indicated that greater identification with same-sex students, same-race students, and same-Greek-status students were associated with stronger relationships between perceived drinking norms in the specific groups and own drinking

The feasibility and effectiveness of a web-based personalised feedback and social norms alcohol intervention in UK university students: A randomised control trial

OBJECTIVE Alcohol misuse amongst University students is a serious concern, and research has started to investigate the feasibility of using e-health interventions. This study aimed to establish the effectiveness of an electronic web-based personalised feedback intervention through the use of a randomised control trial (RCT). METHODS 506 participants were stratified by gender, age group, year of study, self-reported weekly consumption of alcohol and randomly assigned to either a control or intervention condition. Intervention participants received electronic personalised feedback and social norms information on their drinking behaviour which they could access by logging onto the website at any time during the 12-week period. CAGE score, average number of alcoholic drinks consumed per drinking occasion, and alcohol consumption over the last week were collected from participants at pre- and post-survey. RESULTS A significant difference in pre- to post-survey mean difference of alcohol consumed per occasion was found, with those in the intervention condition displaying a larger mean decrease when compared to controls. No intervention effect was found for units of alcohol consumed per week or for CAGE scores. Sixty-three percent of intervention participants agreed that the feedback provided was useful. Those intervention participants who were above the CAGE cut off were more likely to report that the website would make them think more about the amount they drank. CONCLUSIONS Delivering an electronic personalised feedback intervention to students via the World Wide Web is a feasible and potentially effective method of reducing student alcohol intake. Further research is needed to replicate this outcome, evaluate maintenance of any changes, and investigate the process of interaction with web-based interventions

Opponent-process additivity--I: Red/green equilibria

A red/green equilibrium light is one which appears neither reddish nor greenish (i.e. either uniquely yellow, uniquely blue, or achromatic). A subset of spectral and nonspectral red/green equilibria was determined for several luminance levels, in order to test whether the set of all such equilibria is closed under linear color-mixture operations.The spectral loci of equilibrium yellow and blue showed either no variation or visually insignificant variation over a range of 1-2 log10 unit. There were no trends that were repeatable across observers. We concluded that spectral red/green equilibria are closed under scalar multiplication; consequently they are invariant hues relative to the Bezold-Brucke shift.The additive mixture of yellow and blue equilibrium wavelengths, in any luminance ratio, is also an equilibrium light. Small changes of the yellowish component of a mixture toward redness or greeness must be compensated by predictable changes of the bluish component of the mixture toward greenness or redness. We concluded that yellow and blue equilibria are complementary relative to an equilibrium white; that desaturation of a yellow or blue equilibrium light with such a white produces no Abney hue shift; and that the set of red/green equilibria is closed under general linear operations.One consequence is that the red/green chromatic-response function, measured by the Jameson-Hurvich technique of cancellation to equilibrium, is a linear function of the individual's color-matching coordinates. A second consequence of linear closure of equilibria is a strong constraint on the class of combination rules by which receptor outputs are recoded into the red/green opponent process.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22247/1/0000683.pd

Solar System Processes Underlying Planetary Formation, Geodynamics, and the Georeactor

Only three processes, operant during the formation of the Solar System, are responsible for the diversity of matter in the Solar System and are directly responsible for planetary internal-structures, including planetocentric nuclear fission reactors, and for dynamical processes, including and especially, geodynamics. These processes are: (i) Low-pressure, low-temperature condensation from solar matter in the remote reaches of the Solar System or in the interstellar medium; (ii) High-pressure, high-temperature condensation from solar matter associated with planetary-formation by raining out from the interiors of giant-gaseous protoplanets, and; (iii) Stripping of the primordial volatile components from the inner portion of the Solar System by super-intense solar wind associated with T-Tauri phase mass-ejections, presumably during the thermonuclear ignition of the Sun. As described herein, these processes lead logically, in a causally related manner, to a coherent vision of planetary formation with profound implications including, but not limited to, (a) Earth formation as a giant gaseous Jupiter-like planet with vast amounts of stored energy of protoplanetary compression in its rock-plus-alloy kernel; (b) Removal of approximately 300 Earth-masses of primordial gases from the Earth, which began Earth's decompression process, making available the stored energy of protoplanetary compression for driving geodynamic processes, which I have described by the new whole-Earth decompression dynamics and which is responsible for emplacing heat at the mantle-crust-interface at the base of the crust through the process I have described, called mantle decompression thermal-tsunami; and, (c)Uranium accumulations at the planetary centers capable of self-sustained nuclear fission chain reactions.Comment: Invited paper for the Special Issue of Earth, Moon and Planets entitled Neutrino Geophysics Added final corrections for publicatio