An argument for anti-perfectionism

In political philosophy, perfectionism is the view that it is the job of the state to best enable its citizens to live good or flourishing lives. It claims that certain lives can be judged to be sound, and thus instructs governments to promote those lives using state institutions etc. Anti-perfectionism denies this. It says that it is not the job of the state to promote good lives. Instead it should restrict itself to securing basic rights and duties, a threshold level of resources and so on. Citizens should be left to adopt pursuits however they see fit. For some anti-perfectionists, this is precisely because we cannot judge any putative life to be sound. However, many are not sceptics, and justify state neutrality for other reasons. All accounts of anti-perfectionism must overcome what has been called the asymmetry objection: what justifies the imbalance inherent in anti-perfectionism? Why believe that the state is permitted to act on judgements about justice, but not on judgements about flourishing? My thesis argues that attempts to respond to the asymmetry objection have failed thus far. Further, I offer an account of political morality that can overcome the problem. The first four chapters of the thesis clarify the debate between perfectionists and anti-perfectionists, narrowing the former down into its most plausible form. Chapters five and six focus on two failed attempts to vindicate anti-perfectionism – Brian Barry’s argument from scepticism and Jonathan Quong’s Rawlsian approach. In the final chapter I put forward a much more promising argument in favour of anti-perfectionism – justice as a set of constraints

Approaches to carbohydrate-based chemical libraries : the evolution of glycotides

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1995.Includes bibliographical references.by Jason Patrick McDevitt.Ph.D

Process of Compassion: Pastoral Care During School Closings

Catholic education in the United States continues to face mounting economic challenges. Dioceses are being challenged with the painful reality of closing Catholic schools that have long served communities. These school closings leave behind wounded and disillusioned professionals. The Process of Compassion Workshop was developed to provide personal and professional help for healing so that teachers could move forward in their careers. This article provides a theoretical framework with action research to care for the dedicated people school closings leave behind

Transition state for the NSD2-catalyzed methylation of histone H3 lysine 36

Nuclear receptor SET domain containing protein 2 (NSD2) catalyzes the methylation of histone H3 lysine 36 (H3K36). It is a determinant in Wolf–Hirschhorn syndrome and is overexpressed in human multiple myeloma. Despite the relevance of NSD2 to cancer, there are no potent, selective inhibitors of this enzyme reported. Here, a combination of kinetic isotope effect measurements and quantum chemical modeling was used to provide subangstrom details of the transition state structure for NSD2 enzymatic activity. Kinetic isotope effects were measured for the methylation of isolated HeLa cell nucleosomes by NSD2. NSD2 preferentially catalyzes the dimethylation of H3K36 along with a reduced preference for H3K36 monomethylation. Primary Me-(14)C and (36)S and secondary Me-(3)H(3), Me-(2)H(3), 5′-(14)C, and 5′-(3)H(2) kinetic isotope effects were measured for the methylation of H3K36 using specifically labeled S-adenosyl-l-methionine. The intrinsic kinetic isotope effects were used as boundary constraints for quantum mechanical calculations for the NSD2 transition state. The experimental and calculated kinetic isotope effects are consistent with an S(N)2 chemical mechanism with methyl transfer as the first irreversible chemical step in the reaction mechanism. The transition state is a late, asymmetric nucleophilic displacement with bond separation from the leaving group at (2.53 Å) and bond making to the attacking nucleophile (2.10 Å) advanced at the transition state. The transition state structure can be represented in a molecular electrostatic potential map to guide the design of inhibitors that mimic the transition state geometry and charge

The summer undergraduate research experience as a work-integrated learning opportunity and potential pathway to publication in psychology

© 2019 Golding, Breen, Krause and Allen. Unlike disciplines which focus on skill development from year one of a bachelor's degree, training in psychology in Australia follows the scientist-practitioner model. According to this model, an undergraduate psychology degree should focus on the scientific principles underpinning the discipline and provide a foundation for the development of professional skills in graduate school. However, most Australian psychology undergraduates do not continue into graduate school, and concerns have been raised about their lack of applied skills and work-readiness. Work-integrated learning (WIL) refers to strategies aimed at providing students with practical experiences (e.g., fieldwork, placements, and internships) directly related to their course of study. The objective of WIL is to increase work-readiness. Accreditation standards coupled with the norms of the discipline have historically prevented the inclusion of typical WIL experiences in Australian undergraduate psychology degrees. However, one particular type of WIL activity-the undergraduate research experience (URE)-is particularly suited to psychology. In a typical URE, students collaborate with faculty to conduct research designed to make an original contribution to their field. The current study is a qualitative investigation of stakeholder perceptions of a competitive summer URE program ran from 2012 to 2016. Six faculty members and seven undergraduate students were engaged in semi-structured interviews about their URE experiences. Constructed themes broadly reflected the benefits and challenges of the program and included work-readiness and additional research experience, networking and teamwork, publication, quality of experience and equity of opportunities. Faculty members and students spoke favorably of their UREs in most cases, although issues of administration and financial concerns were mentioned consistently, as were concerns about the length, timing, and nature of projects. Students reported skill development and networking as two of the key benefits of their participation in the program, and article publication was seen as particularly beneficial to career prospects. Our findings suggest that student co-authored publications resulting from UREs are possible, but careful thought is required to optimize their likelihood. Overall, this research adds to a growing literature suggesting that UREs can confer a range of benefits to Australian psychology schools related to increased research capacity and student satisfaction

The State of Coral Reef Ecosystems of Southeast Florida

The northern extension of the Florida reef tract and a complex of limestone ridges run parallel to the subtropical Atlantic coastline of southeast Florida. Spanning 170 km from the northern border of Biscayne National Park (BNP) in Miami-Dade County to the St. Lucie Inlet in Martin County, the reefs and hardbottom areas in this region support a rich and diverse biological community (Figure 5.1). Nearshore reef habitats in southeast Florida include hardbottom areas, patch reefs and worm reefs (Phragmatopoma spp.) exhibiting abundant octocoral, macroalgae, stony coral and sponge assemblages. Offshore, coral reef associated biotic assemblages occur on linear Holocene Acropora palmata mid-shelf and shelf margin reefs that extend from Miami Dade County to Palm Beach County (Lighty, 1977; Figure 5.2). Anastasia Formation limestone ridges and terraces colonized by reef biota characterize the reefs from Palm Beach County to Martin County (Cooke and Mossom, 1929). The coastal region of southeast Florida is highly developed, containing one third of Florida’s population of 16 million people (U.S. Census Bureau, 2006). Many southeast Florida reefs are located just 1.5 km from this urbanized shoreline. Despite their unique position as the highest latitude reefs along the western Atlantic seaboard, the reefs of southeast Florida have only recently received limited scientific and resource management attention. Andrews et al. (2005) discussed the reefs of southeast Florida and the critical need to implement actions that fill resource knowledge gaps and address conservation and threats to reef health. This report further examines and updates the list of stressors imperiling the health of southeast Florida’s reefs, and presents information gained from new research, monitoring and management efforts to determine the extent and condition of reef resources in this distinctive region

Smyd3 regulates cancer cell phenotypes and catalyzes histone H4 lysine 5 methylation

Smyd3 is a lysine methyltransferase implicated in chromatin and cancer regulation. Here we show that Smyd3 catalyzes histone H4 methylation at lysine 5 (H4K5me). This novel histone methylation mark is detected in diverse cell types and its formation is attenuated by depletion of Smyd3 protein. Further, Smyd3-driven cancer cell phenotypes require its enzymatic activity. Thus, Smyd3, via H4K5 methylation, provides a potential new link between chromatin dynamics and neoplastic disease

Genetic Evidence for a Tight Cooperation of TatB and TatC during Productive Recognition of Twin-Arginine (Tat) Signal Peptides in Escherichia coli

The twin arginine translocation (Tat) pathway transports folded proteins across the cytoplasmic membrane of bacteria. Tat signal peptides contain a consensus motif (S/T-R-R-X-F-L-K) that is thought to play a crucial role in substrate recognition by the Tat translocase. Replacement of the phenylalanine at the +2 consensus position in the signal peptide of a Tat-specific reporter protein (TorA-MalE) by aspartate blocked export of the corresponding TorA(D+2)-MalE precursor, indicating that this mutation prevents a productive binding of the TorA(D+2) signal peptide to the Tat translocase. Mutations were identified in the extreme amino-terminal regions of TatB and TatC that synergistically suppressed the export defect of TorA(D+2)-MalE when present in pairwise or triple combinations. The observed synergistic suppression activities were even more pronounced in the restoration of membrane translocation of another export-defective precursor, TorA(KQ)-MalE, in which the conserved twin arginine residues had been replaced by lysine-glutamine. Collectively, these findings indicate that the extreme amino-terminal regions of TatB and TatC cooperate tightly during recognition and productive binding of Tat-dependent precursor proteins and, furthermore, that TatB and TatC are both involved in the formation of a specific signal peptide binding site that reaches out as far as the end of the TatB transmembrane segment

Cartography of Methicillin-Resistant S. aureus Transcripts: Detection, Orientation and Temporal Expression during Growth Phase and Stress Conditions

BACKGROUND: Staphylococcus aureus is a versatile bacterial opportunist responsible for a wide spectrum of infections. The severity of these infections is highly variable and depends on multiple parameters including the genome content of the bacterium as well as the condition of the infected host. Clinically and epidemiologically, S. aureus shows a particular capacity to survive and adapt to drastic environmental changes including the presence of numerous antimicrobial agents. Mechanisms triggering this adaptation remain largely unknown despite important research efforts. Most studies evaluating gene content have so far neglected to analyze the so-called intergenic regions as well as potential antisense RNA molecules. PRINCIPAL FINDINGS: Using high-throughput sequencing technology, we performed an inventory of the whole transcriptome of S. aureus strain N315. In addition to the annotated transcription units, we identified more than 195 small transcribed regions, in the chromosome and the plasmid of S. aureus strain N315. The coding strand of each transcript was identified and structural analysis enabled classification of all discovered transcripts. RNA purified at four time-points during the growth phase of the bacterium allowed us to define the temporal expression of such transcripts. A selection of 26 transcripts of interest dispersed along the intergenic regions was assessed for expression changes in the presence of various stress conditions including pH, temperature, oxidative shocks and growth in a stringent medium. Most of these transcripts showed expression patterns specific for the defined stress conditions that we tested. CONCLUSIONS: These RNA molecules potentially represent important effectors of S. aureus adaptation and more generally could support some of the epidemiological characteristics of the bacterium