Human regulatory protein Ki-1/57 has characteristics of an intrinsically unstructured protein

The human protein Ki-1/57 was first identified through the cross reactivity of the anti-CD30 monoclonal antibody Ki-1; in Hodgkin lymphoma cells. The expression of Ki-1/57 in diverse cancer cells and its phosphorylation in peripheral blood leukocytes after mitogenic activation suggested its possible role in cell signaling. Ki-1/57 interacts with several other regulatory proteins involved in cellular signaling, transcriptional regulation and RNA metabolism, suggesting it may have pleiotropic functions. In a previous spectroscopic analysis, we observed a low content of secondary structure for Ki-1/57 constructs. Here, Circular dichroism experiments, in vitro RNA binding analysis, and limited proteolysis assays of recombinant Ki-1/57(122-413) and proteolysis assays of endogenous full length protein from human HEK293 cells suggested that Ki-1/57 has characteristics of an intrinsically unstructured protein. Small-angle X-ray scattering (SAXS) experiments were performed with the C-terminal fragment Ki-1/57(122-413). These results indicated an elongated shape and a partially unstructured conformation of the molecule in solution, confirming the characteristics of an intrinsically unstructured protein. Experimental curves together with ab initio modeling approaches revealed an extended and flexible molecule in solution. An elongated shape was also observed by analytical gel filtration. Furthermore, sedimentation velocity analysis suggested that Ki-1/57 is a highly asymmetric protein. These findings may explain the functional plasticity of Ki-1/57, as suggested by the wide array of proteins with which it is capable of interacting in yeast two-hybrid interaction assays.

Skeletal muscle total creatine content and creatine transporter gene expression in vegetarians prior to and following creatine supplementation

This study examined the effect of vegetarianism on skeletal muscle total creatine (TCr) content and creatine transporter (CreaT) gene expression, prior to and during 5 d of Cr supplementation (CrS). In a double-blind, crossover design, 7 vegetarians (VEG) and nonvegetarians (NVEG) were assigned Cr or placebo supplements for 5 d and after 5 wk, received the alternative treatment. Muscle sampling occurred before, and after 1 and 5 d of treatment ingestion. Basal muscle TCr content was lower (P &lt; 0.05) in VEG compared with NVEG. Muscle TCr increased (P &lt; 0.05) throughout the Cr trial in both groups but was greater (P &lt; 0.05) in VEG compared with NVEG, at days 1 and 5. CreaT gene expression was not different between VEG and NVEG. The results indicate that VEG have a lower muscle TCr content and an increased capacity to load Cr into muscle following CrS. Muscle CreaT gene expression does not appear to be affected by vegetarianism.<br />

The minimum moral content of law : a critique of Hart's descriptive theory of positive and natural law

Review of H.L.A. Hart's account of the minimum moral content of law - assesses its consistency with the methodology provided in his description of the focal meaning or central case of law - particular focus is Hart's consideration of the ultimate end of man - how difficulties faced by Hart's account of the minimum moral content of law can be overcome.<br />

Giving content to the principle of proportionality: happiness and pain as the universal currency for matching offence seriousness and penalty severity

The principle of proportionality prescribes that the punishment should equal the crime. It is one of the most important principles of sentencing. Yet, despite its widespread acceptance it offers no meaningful guide to sentencing. Hence penalty levels fluctuate greatly between jurisdictions and within jurisdictions. This is because there is no universally agreed criterion for measuring offence seriousness or penalty severity. This article suggests that the appropriate criteria for matching offence seriousness and penalty severity is the level of unhappiness or pain stemming from each of these impositions. Thus, for example, the level of pain meted out to a rape offender should equal the level of pain caused to a rape victim. Emerging scientific studies on human well-being and happiness show that human beings are similarly built in terms of the experiences that are either conducive or inimical to well-being. This commonality provides a strong foundation to be confident to make reasonably accurate predictions concerning the extent to which adverse events, such as being the victim of a criminal offence or subjected to a form of criminal sanction will stifle human flourishing. This will then allow us to match accurately offence seriousness and penalty level.

User-generated content and the changing news cycle

Blogs represent a major development in media consumption and practice.&nbsp; The Pew Center in the United States reported in mid-2005 that about eight million Americans had created blogs and 32 million read them.&nbsp; That's equivalent to two-thirds the number of people who read a daily newspaper during a week, a challenging giguew in the context of dwindling circulations.&nbsp; Blogs represent the start of the 'personal media' revolution, but are only the tip of a range of new media developments.&nbsp; This paper describes the blog phenomenon and notes its arrival via a series of major new stories.&nbsp; It suggests we are seeing the emergence of a new news cycle, as blogs and other internet-based media usurp broadcast's role in breaking news.&nbsp; The paper describes a range of emerging digital journalism forms that make up the 'personal media' revolution.&nbsp; These include blogs delivered via mobile phones (moblogs); video-based blogs (v-logs); newspapers' use of podcasting to deliver content; and wikis, or peer-generated online content. The media's reaction to this new form of content is described, and the other concludes by looking at the forces driving this new form of journalism.

An approach to search and exploration through mixed-initiative

Generative design environments need support for human intervention as well as sound computational formalisms. A systematic approach to integrating the two, formal generation and the exploratory, is lacking. In this paper, we posit the possibility of a design support system that combines formal search with user driven exploration. Our approach is to cast the interaction between the user and the generative formalism as agent collaboration in a mixed-initiative environment. We describe the role of interaction and agency in an experimental mixed-initiative design support system, <b><i>FOLDS</i></b> and demonstrate its application.<br />

Effects of endurance training status and sex difference on Na+, K+-pump mRNA expression, content and maximal activity in human skeletal muscle

<b>Aim</b>: This study investigated the effects of endurance training status and sex differences on skeletal muscle Na⁺,K⁺-pump mRNA expression, content and activity. <b>Methods</b>: Forty-five endurance-trained males (ETM), 11 recreationally active males (RAM), and nine recreationally active females (RAF) underwent a vastus lateralis muscle biopsy. Muscle was analysed for Na⁺,K⁺-pump &alpha;1, &alpha;2, &alpha;3, &beta;1, &beta;2 and &beta;3 isoform mRNA expression (real-time reverse transcription-polymerase chain reaction), content ([³H]-ouabain-binding site) and maximal activity (3-O-methylfluorescein phosphatase, 3-O-MFPase). <b>Results</b>: ETM demonstrated lower &alpha;1, &alpha;3, &beta;2 and &beta;3 mRNA expression by 74%, 62%, 70% and 82%, respectively, than RAM (<i>P</i> &lt; 0.04). In contrast, [³H]-ouabain binding and 3-O-MFPase activity were each higher in ETM than in RAM, by 16% (<i>P</i> &lt; 0.03). RAM demonstrated a 230% and 364% higher &alpha;3 and b3 mRNA expression than RAF, respectively (P &lt; 0.05), but no significant sex differences were found for &alpha;1, &alpha;2, &beta;1 or &beta;2 mRNA, [³H]-ouabain binding&nbsp; or 3-O-MFPase activity. No significant correlation was found between years of endurance training and either [³H]-ouabain binding or 3-O-MFPase activity. Significant but weak correlations were found between the number of training hours per week and 3-O-MFPase activity (<i>r</i> = 0.31, <i>P</i> &lt; 0.02) and between incremental exercise<b> V</b> O_2(peak) and both&nbsp;&nbsp; [³H]-ouabain binding (<i>r</i> = 0.33, <i>P</i> &lt; 0.01) and 3-O-MFPase activity (<i>r</i> = 0.28, <i>P </i>&lt; 0.03). <b>Conclusions</b>: Isoform-specific differences in Na⁺,K⁺-pump mRNA expression were found with both training status and sex differences, but only training status influenced Na⁺,K⁺-pump content and maximal activity in human skeletal muscle.<br />

Effect of 2 weeks of endurance training on uncoupling protein3 content in untrained human subjects

<b>Aim</b>: The mitochondrial uncoupling protein-3 (UCP3) is able to lower the proton gradient across the inner mitochondrial membrane, thereby uncoupling substrate oxidation from ATP production and dissipating energy as heat. What the effect of endurance training on UCP3 is, is still&nbsp; controversial. Endurance-trained athletes are characterized by lower levels of UCP3, but longitudinal studies in rodents reported no effect of endurance training on muscular UCP3 levels. Here, we examined the effect of a 2-week training programme on skeletal muscle UCP3 protein content in untrained human subjects, and hypothesized that UCP3 will be reduced after the training programme. <b>Methods</b>: Nine untrained men [age: 23.3&plusmn;3.2 years; BMI: 22.6&plusmn;2.6 kg m^-2; maximal power output (^Wmax): 3.8&plusmn;0.6 W kg^-1 body weight] trained for 2 weeks. Before and at least 72 h after the training period, muscle biopsies were taken for determination of UCP3 protein content. <b>Results</b>: UCP3 protein content tended to be lower after the training programme [95&plusmn;10 vs. 109&plusmn;12 arbitrary units (AU), <i>P</i>= 0.08]. Cytochrome <i>c </i>content tended to increase with 33% in response to endurance training (52&plusmn; 6 vs. 39&plusmn; 6 AU, <i>P</i> = 0.08). The ratio UCP3 relative to cytochrome <i>c</i> tended to decrease significantly upon endurance training (2.0&plusmn;0.4 vs. 3.2&plusmn;0.6 AU, <i>P</i> = 0.01). <b>Conclusion</b>: A short-term (2-week) endurance training programme decreased UCP3 protein levels and significantly reduced the ratio of UCP3 to cytochrome <i>c</i>.<br />

Repeated-viewing and co-viewing of an animated video : an examination of factors that impact on young children's comprehension of video content

The experiment reported here was concerned with the effect of repeat- viewing and adult co-viewing on the comprehension of an animated feature length movie. Four- to six-year-old children watched a movie on video either once or five times, and either with their mother present or on their own. The findings revealed that, after controlling for language skills and interest in the type of video watched, children who watched five times had higher comprehension scores than children who watched only once. Furthermore, children who watched the video repeatedly were also better at character identification and at identifying the good and bad qualities of one of the main characters in the movie. The presence of a mother, who was explicitly asked to co- view the movie with her child, did not facilitate comprehension. The findings are discussed in terms of the educational benefits of repeat viewing. Theoretical implications are also noted.<br />

Critical appraisal of health literacy indices revealed variable underlying constructs, narrow content and psychometric weaknesses

<b>Objective</b><br />Health literacy refers to an individual's ability to seek, understand, and use health information. A range of indices exist that purport to measure health literacy across individuals and populations. This study aimed to review the development and content of existing indices and to critically appraise their properties.<br /><br /><b>Study Design and Setting</b><br />Using standardized search terms, published generic health literacy indices (1990&ndash;2008) were identified. Using a methodological framework, each was evaluated for purpose, validity (face, content, construct), reliability, responsiveness, feasibility, and generalizability.<br /><br /><b>Results</b><br />Nineteen instruments were evaluated. Three measurement approaches were identified: direct testing of individual abilities, self-report of abilities, and population-based proxy measures. Composition of underlying constructs and content varied widely across instruments, and none appeared to fully measure a person's ability to seek, understand, and use health information. The content was focused primarily on reading comprehension and numeracy; scoring categories were poorly defined and may not be mutually exclusive, and few indices had been assessed for reliability.<br /><b><br />Conclusion</b><br />Health literacy is not consistently measured, making it difficult to interpret and compare health literacy at individual and population levels. Empirical evidence demonstrating validity and reliability of existing indices is required, and more comprehensive health literacy instruments need to be developed.<br />

Sharable file searching in unstructured peer-to-peer systems

The existing sharable file searching methods have at least one of the following disadvantages: (1) they are applicable only to certain topology patterns, (2) suffer single point failure, or (3) incur prohibitive maintenance cost. These drawbacks prevent their effective application in unstructured Peer-to-peer (P2P) systems (where the system topologies are changed time to time due to peers' frequently entering and leaving the systems), despite the considerable success of sharing file search in conventional peer-to-peer systems. Motivated by this, we develop several fully dynamic algorithms for searching sharing files in unstructured peer to peer systems. Our solutions can handle any topology pattern with small search time and computational overhead. We also present an in-depth analysis that provides valuable insight into the characteristics of alternative effective search strategies and leads to precision guarantees. Extensive experiments validate our theoretical findings and demonstrate the efficiency of our techniques in practice.

Above the bottom line : understanding Australian screen content producers

The recently completed Australian Screen Producer Survey provides the most current and detailed picture of the culture, motivations and aspirations of a highly influential sector of the content production industries. Drawing upon the results of the survey, this article reflects on the historical and theoretical difficulties entailed in defining the producer as a professional category, before outlining some of the survey&rsquo;s key findings. In particular, it examines producers&rsquo; demographic and sectoral profile, analyses their attitudes towards the relative importance of education and experience, and explores their underlying motivations. Amongst other findings, the survey reveals a tendency towards idealism among Australian producers that would appear to be at odds with the financial realities of the business. It therefore offers a variety of stakeholders (including government and educational institutions, as well as producers themselves) with the opportunity to reflect upon the future shape and direction of the Australian media industry.<br />

Watermarking protocol for protecting user's right in content based image retrieval

Content based image retrieval (CBIR) is a technique to search for images relevant to the user&rsquo;s query from an image collection.In last decade, most attention has been paid to improve the retrieval performance. However, there is no significant effort to investigate the security concerning in CBIR. Under the query by example (QBE) paradigm, the user supplies an image as a query and the system returns a set of retrieved results. If the query image includes user&rsquo;s private information, an untrusted server provider of CBIR may distribute it illegally, which leads to the user&rsquo;s right problem. In this paper, we propose an interactive watermarking protocol to address this problem. A watermark is inserted into the query image by the user in encrypted domain without knowing the exact content. The server provider of CBIR will get the watermarked query image and uses it to perform image retrieval. In case where the user finds an unauthorized copy, a watermark in the unauthorized copy will be used as evidence to prove that the user&rsquo;s legal right is infringed by the server provider.<br />