2,927 research outputs found

    Modular Regularization Algorithms

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    From Modern Utopia to Liquid Modern Anti-Utopia?

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    Suffering in the Sociology of Zygmunt Bauman

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    The topic of human suffering loomed large throughout the writings of Zygmunt Bauman. If anything, his work can be characterized as a ‘sociology of suffering’. From the early writings until his very last, suffering constituted a key concern in Bauman’s description of the transformation of society from a solid-modern to a liquid-modern outlook. In his work, there are certain shifts in who and what he regards as the embodiments or expressions of suffering, and there is thus a keen eye on the changing landscape of suffering, its causes and consequences, from past to present. But there is nevertheless always a continuous and vehement defence for those living at the outskirts or at the bottom of society. The article will also explore what Bauman suggest should be done about the presence of suffering, and the article will briefly discuss the viability of his ideas on a morality of proximity as a way to alleviate suffering

    Fear and Retrotopia – Critical Reflections on the Rise of Defensive Emotions in Liquid Modernity

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    This article critically addresses the contemporary study of what is called 'defensive emotions' such as fear and nostalgia among a number of social theorists. While it may be true that the collective emotions of fear and nostalgia (here framed by the phrase of 'retrotopia') may indeed be on the rise in Western liberal democracies, it is also important to be wary of taking the literature on the matter as a sign that fear and nostalgia actually permeate all levels of culture and everyday life. The article starts out with some reflections on the sociology of emotions and shows how the early interest in emotions (theoretical and empirical) among a small group of sociologists is today supplemented with the rise of a critical social theory using collective emotions as a lens for conducting a critical analysis of the times. Then the article in turn deals with the contemporary interest within varuious quarters of the social sciences with describing, analysing and diagnosing the rise of what is here called 'defensive emotions' – emotions that express and symbolize a society under attack and emotions that are mostly interpreted as negative signs of the times. This is followed by some reflections on the collective emotions of fear and nostalgia/retrotopia respectively. The article is concluded with a discussion of how we may understand and assess this relatively new interest in defensive emotions

    Doctor of Philosophy

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    dissertationChemical protein synthesis, via solid-phase peptide synthesis and chemoselective ligation of peptides, is a powerful approach for preparing peptides and proteins. These techniques enable complete atomic control over protein composition with both mechanistic and practical applications for biochemistry. The foundation of this dissertation is formed by two ambitious chemical protein synthesis projects: DapA (Chapter 2) and Dpo4 (Chapter 5). DapA is a 312-residue protein whose folding depends on the well-studied chaperone GroEL/ES. The successful synthesis of DapA (in both L- and D- chirality) was used to demonstrate cross-chiral folding by GroEL/ES-a fundamental biological insight and potential tool for future mirror-image synthetic biology research. However, the record-breaking synthesis of DapA was an arduous process requiring tremendous human and technical resources. The lessons from this project were then applied to the synthesis of our next target, Dpo4 (352 residues). Dpo4 is one of the shortest DNA/RNA polymerases, providing an accessible synthetic tool to amplify DNA/RNA for future synthetic biology studies. A new concept termed DOPPEL (Diversity-based Optimization of Peptide Properties to Enhance Ligations) was used to simplify this synthesis. Furthermore, various synthesis strategies and general advice for completing ! ! iv mega-synthesis projects in the future are detailed in this chapter. In both the DapA and Dpo4 projects, one of the most prominent challenges was the handling of poorly soluble peptide segments. These poorly soluble peptides can lead to dramatic yield losses and additional complexities. In the third major synthesis project of this thesis, GroES, we overcame an even greater insolubility challenge. This 97-residue protein could not be synthesized due to extreme solubility challenges with its C-terminal half. In response to this challenge, a new chemical tool was developed to link a solubilizing peptide ("Helping Hand") to the C-terminal half of the protein. Key to this approach is a new synthetic building block, Fmoc-Ddae-OH, which is easy to synthesize, incorporate, and cleanly remove once the solubilizing function is complete. Overall, this dissertation pushes the limits of chemical peptide and protein synthesis, and provides exciting directions for the next wave of biochemists looking to use chemical protein synthesis to study interesting problems and engineering challenges

    Peptide processing via silk-inspired spinning enables assembly of multifunctional protein alloy fibers

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    Diverse fiber-forming proteins are found in nature that accomplish a wide range of functions including signaling, cell adhesion, and mechanical support. Unique sequence characteristics of these proteins often lead to their specialized roles. However, these proteins also share a common organizational hierarchy in primary and secondary structures that strongly influence both their intramolecular folding and intermolecular interactions. Based on what is known regarding protein fiber assembly of silk peptides, shear-induced elongation of the molecular strands drives interchain secondary structure crystallization via anisotropic alignment, which creates a molecular superstructure that forms the basis a fiber network. In this work, the hypothesis is this type of protein fiber assembly is not unique to silk sequences and that other proteins can be spun into fibers in similar fashion while maintaining unique functionality given by their specialized amino acid sequences such as RGD, GX1X2, and so forth. This was investigated by modeling the manner in which hydrophobic and hydrophilic blocks of amino acids create interacting secondary structures at the chain level when exposed to shear. It was determined computationally and then verified experimentally that fiber spinning success is most likely to occur after shear processing if the protein sequence exhibits a balance of hydrophobic and hydrophilic content and has sufficient length. Applied to the biological scale, both pure and mixed solutions of proteins such as fibronectin, laminin, and silk fibroin were spun into fibers. In particular, alloy protein fibers of silk fibroin mixed with fibronectin exhibited the characteristic mechanical integrity of silk and the bioactivity of fibronectin. This simple method of creating protein fibers with hybrid characteristics is significantly faster, less expensive, and less technically intensive than chimeric protein production, which purports to do the same. This finding also provides insight into a fundamental means by which protein fibers may be assembled in vivo by taking advantage of the thermodynamically favorable assembly of peptide sequences at the chain level under proper molecular orientation. Taken together, a high throughput means of producing a wide-range of pure and hybrid protein fibers has been developed for various biological applications and research investigations into the fibrous elements of biology

    Can a Home-based Cardiac Physical Activity Program Improve the Physical Function Quality of Life in Children with Fontan Circulation?

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    Objective Patients after Fontan operation for complex congenital heart disease (CHD) have decreased exercise capacity and report reduced health-related quality of life (HRQOL). Studies suggest hospital-based cardiac physical activity programs can improve HRQOL and exercise capacity in patients with CHD; however, these programs have variable adherence rates. The impact of a home-based cardiac physical activity program in Fontan survivors is unclear. This pilot study evaluated the safety, feasibility, and benefits of an innovative home-based physical activity program on HRQOL in Fontan patients. Methods A total of 14 children, 8–12 years, with Fontan circulation enrolled in a 12-week moderate/high intensity home-based cardiac physical activity program, which included a home exercise routine and 3 formalized in-person exercise sessions at 0, 6, and 12 weeks. Subjects and parents completed validated questionnaires to assess HRQOL. The Shuttle Test Run was used to measure exercise capacity. A Fitbit Flex Activity Monitor was used to assess adherence to the home activity program. Results Of the 14 patients, 57% were male and 36% had a dominant left ventricle. Overall, 93% completed the program. There were no adverse events. Parents reported significant improvement in their child\u27s overall HRQOL (P \u3c .01), physical function (P \u3c .01), school function (P = .01), and psychosocial function (P  \u3c .01). Patients reported no improvement in HRQOL. Exercise capacity, measured by total shuttles and exercise time in the Shuttle Test Run and calculated VO2max, improved progressively from baseline to the 6 and 12 week follow up sessions. Monthly Fitbit data suggested adherence to the program. Conclusion This 12-week home-based cardiac physical activity program is safe and feasible in preteen Fontan patients. Parent proxy-reported HRQOL and objective measures of exercise capacity significantly improved. A 6-month follow up session is scheduled to assess sustainability. A larger study is needed to determine the applicability and reproducibility of these findings in other age groups and forms of complex CHD

    New Risks Ahead:The Eastward Enlargement of the Eurozone

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    Eastward enlargement is one of the hot topics in European economics. The accession of central and eastern European Countries (CEEC) into the European Union (EU) is accompanied by an extension of the eurozone to this region. This paper surveys likely outcomes and challenges of this specific feature of EU enlargement. Moreover, the ar-ticle represents the start of an international research project dealing with these ques-tions. Research is structured along different markets. Hence, the impact of an adoption of the euro is analysed for capital and labour markets as well as with respect to exchange rate and monetary policies. Our main position is that the euro has in general beneficiary ef-fects for the CEEC and the current EU in all examined markets. However, these bene-fits evolve mainly in the long run, whereas the short-term costs of adaptation to the new situation may be high. Although we believe that the present value of long-term benefits exceeds these costs, it is by no means clear that policy-makers will share this view. Due to the usual political-economy transformation, the assessment of costs and benefits may be different for politicians than compared to any overall perspective. If of-ficial policies become unforeseeable, so will private behaviour. International investors may reverse their capital flows, draining precious liquidity, and leading to currency and financial crises whenever they perceive the authorities’ commitment to EMU less credi-ble. This article highlights some thinkable mechanisms how any such crisis could evolve. It, thus, sets the agenda for further research, mainly, with the focus on appropriate policy strategies to keep adaptation costs as low as possible, minimise other external risks, without hampering the long-term benefits.EMU, EU enlargement, monetary integration

    Internet-Based Natural Resource Extension

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    The growth of the Internet, combined with the shifting demographics of private forest landowners that indicate increasing Internet use, presents great opportunities for natural resource extension. The study described here created two natural resource Web sites. An online survey of Pennsylvania forest landowners, foresters, Extension agents, and natural resource teachers examined their demographics, evaluated Web site effectiveness, and determined what site features the audience preferred. The groups had varied learning interests and would use Web sites in different ways. The Internet is an important addition to the natural resource learning community and must be tailored to suit different users needs

    Synchrotron Mössbauer spectroscopic study of ferropericlase at high pressures and temperatures

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    The electronic spin state of Fe^(2+) in ferropericlase, (Mg_(0.75)Fe_(0.25))O, transitions from a high-spin (spin unpaired) to low-spin (spin paired) state within the Earth’s mid-lower mantle region. To better understand the local electronic environment of high-spin Fe^(2+) ions in ferropericlase near the transition, we obtained synchrotron Mössbauer spectra (SMS) of (Mg_(0.75),Fe_(0.25))O in externally heated and laser-heated diamond anvil cells at relevant high pressures and temperatures. Results show that the quadrupole splitting (QS) of the dominant high-spin Fe^(2+) site decreases with increasing temperature at static high pressure. The QS values at constant pressure are fitted to a temperature-dependent Boltzmann distribution model, which permits estimation of the crystal-field splitting energy (Δ_3) between the d_(xy_ and d_(xz) or d_(zy) orbitals of the t_(2g) states in a distorted octahedral Fe^(2+) site. The derived Δ_3 increases from approximately 36 meV at 1 GPa to 95 meV at 40 GPa, revealing that both high pressure and high temperature have significant effects on the 3d electronic shells of Fe^(2+) in ferropericlase. The SMS spectra collected from the laser-heated diamond cells within the time window of 146 ns also indicate that QS significantly decreases at very high temperatures. A larger splitting of the energy levels at high temperatures and pressures should broaden the spin crossover in ferropericlase because the degeneracy of energy levels is partially lifted. Our results provide information on the hyperfine parameters and crystal-field splitting energy of high-spin Fe^(2+) in ferropericlase at high pressures and temperatures, relevant to the electronic structure of iron in oxides in the deep lower mantle
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