Zeitschriftenartikel zum Thema „Cycling arena“

This case describes the motivation, challenges, and opportunities the founder of an innovative cycling product experienced as he attempted to use crowdfunding as a platform to establish and grow his business idea. The case begins with a brief overview of how the entrepreneur came up with the idea and the journey from product concept to product launch. The decision to crowdfund the idea is explained and the challenges and opportunities in trying to navigate the crowdfunding arena are explored; from selecting a suitable crowdfunding platform to the launch and management of the final campaign. Despite the fact the campaign failed to raise the funding target, the media coverage from the crowdfunding campaign led to a number of significant business avenues, which ultimately helped launch the product onto the marketplace. The case examines these events and closes as the entrepreneur reflects on the lessons learnt from the experience and his advice going forward to anyone considering crowdfunding.

Purpose The purpose of this paper is to explore the meanings of walkability and relevance for tourism in modern Asian cities, including barriers to its implementation. Particular reference is made to conditions in the city state of Singapore and the manner in which urban planning and transport policies are influencing the tourist walking experience. Design/methodology/approach A case study methodology was selected as most suitable for the exercise accompanied by a literature review. Findings are derived from material in the public arena collected from a range of sources. Findings The government is shown to be actively pursuing policies to encourage both walking and cycling by residents as components of wider strategies directed at improving liveability. Several initiatives which positively affect the comfort and enjoyment of city walking by tourists are identified, but so too are Singapore’s shortcomings as a destination in which to walk. Balancing the demands on public space is a critical challenge for authorities. Originality/value The subject has been neglected within both an urban tourism and Asian city context and this paper illuminates aspects of significance pertaining to the concept and practice of walkability. Insights are afforded into factors which facilitate walkability and impediments to overcome.

A century after the identification of a coenzymatic activity for NAD+, NAD+ metabolism has come into the spotlight again due to the potential therapeutic relevance of a set of enzymes whose activity is tightly regulated by the balance between the oxidized and reduced forms of this metabolite. In fact, the actions of NAD+ have been extended from being an oxidoreductase cofactor for single enzymatic activities to acting as substrate for a wide range of proteins. These include NAD+-dependent protein deacetylases, poly(ADP-ribose) polymerases, and transcription factors that affect a large array of cellular functions. Through these effects, NAD+ provides a direct link between the cellular redox status and the control of signaling and transcriptional events. Of particular interest within the metabolic/endocrine arena are the recent results, which indicate that the regulation of these NAD+-dependent pathways may have a major contribution to oxidative metabolism and life span extension. In this review, we will provide an integrated view on: 1) the pathways that control NAD+ production and cycling, as well as its cellular compartmentalization; 2) the signaling and transcriptional pathways controlled by NAD+; and 3) novel data that show how modulation of NAD+-producing and -consuming pathways have a major physiological impact and hold promise for the prevention and treatment of metabolic disease.

Gravel-bed river floodplains in mountain landscapes disproportionately concentrate diverse habitats, nutrient cycling, productivity of biota, and species interactions. Although stream ecologists know that river channel and floodplain habitats used by aquatic organisms are maintained by hydrologic regimes that mobilize gravel-bed sediments, terrestrial ecologists have largely been unaware of the importance of floodplain structures and processes to the life requirements of a wide variety of species. We provide insight into gravel-bed rivers as the ecological nexus of glaciated mountain landscapes. We show why gravel-bed river floodplains are the primary arena where interactions take place among aquatic, avian, and terrestrial species from microbes to grizzly bears and provide essential connectivity as corridors for movement for both aquatic and terrestrial species. Paradoxically, gravel-bed river floodplains are also disproportionately unprotected where human developments are concentrated. Structural modifications to floodplains such as roads, railways, and housing and hydrologic-altering hydroelectric or water storage dams have severe impacts to floodplain habitat diversity and productivity, restrict local and regional connectivity, and reduce the resilience of both aquatic and terrestrial species, including adaptation to climate change. To be effective, conservation efforts in glaciated mountain landscapes intended to benefit the widest variety of organisms need a paradigm shift that has gravel-bed rivers and their floodplains as the central focus and that prioritizes the maintenance or restoration of the intact structure and processes of these critically important systems throughout their length and breadth.

This article contributes to the canon of literature on spectator emotions by examining spectator emotions at a major hallmark event. Spectator experience emotions were surveyed via an online questionnaire resulting in 188 valid responses. This resulted in three groups of spectators being surveyed: 1) those who watched live from the roadside, 2) those watching via a spectator viewing hub, and 3) those watching on television. Variables tested were via PANAS scale emotions. They included the positive emotions of interested, excited, strong, enthusiastic, proud, alert, inspired, determined, attentive, and active. The negative emotions were distressed, upset, hostile, irritable, scared, nervous, afraid, guilty, ashamed, and jittery. There are also nine categories within the model, which are (1) attentive, (2) excited, (3) proud, (4) strong, (5) distressed, (6) angry, (7) fearful, (8) guilty, and (9) nervous. The highest positive value feelings of "interested, excited, and enthusiastic" occurred during the live action by those watching on the roadside. Negative feelings were more variable but a highest rating for "afraid" increased during the event, suggesting feelings of not wanting to miss anything (action). Further exploration of the emotions experienced before, during, and after an event is required in order to more fully understand the complexity of the factors. For those planning and staging cycling and similar multistage or multisite events the mapping (route) and layout of the active spectator and participant arena can be carefully constructed to provide potential emotional hot spots. Emotions vary across time and this appears to be related to mode and location of spectating. It implies that event organizers can utilize different "experiential components" within an event setting to create conditions that would be conducive to an optimal viewing environment.

Abstract. The Earth's Critical Zone (CZ) is the critical, outer shell of the Earth that provides an arena for the interplay of diverse physical, chemical, and biological processes that are fundamental for sustaining life. As microbes are the principle drivers of biogeochemical cycles, it is necessary to understand the biodiversity of the CZ unseen majority and their impact on life-sustaining processes. This review aims to summarize the factors controlling where microbes (prokaryotes and micro-eukaryotes) live within the CZ and what is known to date about their diversity and function. Microbes live in all regions of the CZ down to 5 km depth, but due to changing habitat complexity, e.g., variability in pore spaces, water, oxygen, and nutrients, their functional role changes with depth. The abundance of prokaryotes and micro-eukaryotes decreases from a maximum of 1010 or 107 cells g soil−1 up to eight orders of magnitude with depth. Symbiotic mycorrhizal fungi and free-living decomposers are best understood in soil habitats, where they are up to 103 cells g soil−1. However, little is known about their identity and impact on weathering in the deep subsurface. The relatively low abundance of micro-eukaryotes in the deep subsurface suggests that these organisms are either limited in space or nutrients or unable to cope with oxygen limitations. Since deep regions of the CZ are limited in the recent input of photosynthesis-derived carbon, microbes are dependent on deposited organic material or on chemolithoautotrophic metabolism that allows for the establishment of a complete food chain independent from the surface. However, the energy flux available might only allow cell growth over tens to thousands of years. The recent development of "omics" technologies has provided microbial ecologists with methods to link the composition and function of in situ microbial communities. We should expect new metabolic discoveries as we have a closer look utilizing a polyphasic approach into the microbial communities of the CZ. Thus, future work is still needed to link microbial biodiversity to the exact role of microbes in weathering and geochemical cycling in the CZ, especially in subsurface habitats.

The Jewish population in Volhynia constituted 9.9% of the province’s total population (205,500 as of 1931). Jews were the largest national group living in cities, about 48.6%. Jewish urban population constituted 13% of the total population and were very active in sports activities. They attended instructor courses in various sports areas and actively created regional branches of sports associations in Volhynia. The most popular sports among the Jewish population were football, boxing, cycling, athletics and skiing. Jewish athletes successfully competed in different sports events in the provincial, national and international arenas. Football players of the Hasmonea Równe club won the title of the best football team in the province of Volhynia three times. After winning the Volhynia Regional Football Association football team, the Hasmonea Równe junior football team participated in the Polish Championships for junior teams. Jewish footballers from the province of Volhynia participated in the matches of the representations of the cities, the word of Province Volhynia, and the national sports competitions of the Polish Makkabi teams. Representatives of other sports disciplines such as boxing, cycling and skiing also successfully competed at the regional (provincial) level.

Astrobiology is an extremely wide-ranging field and thus is in special need of conceptual and theoretical frameworks that can integrate its various arenas of study. In this paper I review recent work associated with a conceptual framework known as ‘ecological stoichiometry’ and even more recent extensions in the development of ‘biological stoichiometry’. Ecological stoichiometry is the study of the balance of energy and multiple chemical elements in ecological interactions and has developed rapidly in the study of nutrient cycling and energy flow in aquatic food webs. It identifies the elemental composition of interacting biota as central in understanding the nature of their interactions and dynamics, including key feedbacks via nutrient recycling. Biological stoichiometry extends this mode of thinking to all types of biological systems. It especially seeks to better understand, at the biochemical and genetic levels, the factors influencing the elemental composition of living things and the evolutionary forces that drive and constrain that elemental composition. By connecting key concepts of ecosystem ecology, evolutionary biology and biochemistry, stoichiometric theory integrates biological information into a more coherent whole that holds considerable promise for application in astrobiology. Several examples of potential astrobiological applications of stoichiometric analysis are offered, including ones related to pre-biotic evolution, the Cambrian explosion, biosignatures and biological feedbacks on planetary carbon cycling.

This article compares the efforts to govern performance enhancement technologies in two seemingly different competitive arenas—financial markets and professional cycling—where the pressures to outperform are enormous. In the two decades prior to the 2007 financial crisis, new derivative financial commodities such as collateralized debt obligations (CDOs) were created to “juice up” investment returns for extraordinary profits. Over roughly the same period, the development and use of blood boosting drugs and technologies brought so-called doping by cyclists to new levels of complexity and sophistication with extraordinary race results and new levels of commercialization of the sport. The efforts to “turbocharge” their respective competitive spaces took place within complicated regimes of self-regulation that had strikingly dissimilar narratives about performance enhancement and, consequently, different technologies for control. Looking across these seemingly disparate cases draws our attention to how regulation fits into the assemblage of competition and prospects for reform.

The cyclin D/cyclin-dependent kinases 4 and 6 (CDK4/6)–retinoblastoma protein (RB) pathway plays a key role in the proliferation of both normal breast epithelium and breast cancer cells. A strong rationale for inhibiting CDK4/6 in breast cancers has been present for many years. However, potent and selective CDK4/6 inhibitors have only recently become available. These agents prevent phosphorylation of the RB tumor suppressor, thereby invoking cancer cell cycle arrest in G1. CDK4/6 inhibitors have transited rapidly from preclinical studies to the clinical arena, and three have already been approved for the treatment of advanced, estrogen receptor (ER)-positive breast cancer patients on account of striking clinical trial results demonstrating substantial improvements in progression-free survival. ER-positive breast cancers harbor several molecular features that would predict their sensitivity to CDK4/6 inhibitors. As physicians gain experience with using these agents in the clinic, new questions arise: are CDK4/6 inhibitors likely to be useful for patients with other subtypes of breast cancer? Are there other agents that could be effectively combined with CDK4/6 inhibitors, beyond endocrine therapy? Is there a rationale for combining CDK4/6 inhibitors with novel immune-based therapies? In this review, we describe not only the clinical data available to date, but also the biology of the CDK4/6 pathway and discuss answers to these questions. In particular, we highlight that CDK4 and CDK6 govern much more than the cancer cell cycle, and that their optimal use in the clinic depends on a deeper understanding of the less well characterized effects of these enzymes.

Attention has not hitherto been turned intently to the popularity of particular branches of sports in the research of the history of Estonian sports. It has more intuitively been believed that the most popular branch of sports in the pre-war Republic of Estonia (1918–1940) was football. The conspicuously extensive coverage of football in the periodical press has provided grounds for this belief. Compared to other sports games and the more major individual branches, football had the most international matches at the level of national teams, which attracted thousands of spectators. Estonian clubs annually hosted squads from neighbouring countries. Professional clubs mainly from Central Europe brought thousands of spectators to the stadiums in the latter half of the 1920s and in the early 1930s. Rivalries between squads at home were also of great interest to the public and the media. The other primary ball games, basketball and volleyball, started being played in Estonia some ten years after football, and their position was weaker internationally as well: contacts between countries were infrequent. The international basketball association was established in 1932 and its analogue in volleyball was founded in 1947. Track and field, the largest branch of individual athletics, also could not compete with football in terms of matches and international contacts. This article is the first more serious attempt to compare the popularity of branches of sports in Estonia in the 1920s and 1930s. I compared the more major branches of sports in four categories: the number of participants in the particular branch of sports, the sizes of audiences, their ability to cope economically (balance sheets and revenue reports), and their position in the print media. The fact that there are gaps in the data in both the archives and in periodicals, and that the information for different years does not always match, made comparison of the numbers of participants difficult. The methodology used for ascertaining the number of participants was also not necessarily the same. An adequate comparison to the more important individualsports branches is complicated to arrive at because until 1933, the Eesti Kerge-, Raske- ja Veespordiliit (Estonian Association of Track and Field, Heavy Athletics and Aquatic Sports) was the umbrella organisation for major branches of sports such as track and field, wrestling, weightlifting, boxing, swimming, diving, gymnastics and cycling, whereas the last two sports branches are not even mentioned in the association’s name. Conclusions can nevertheless be drawn concerning the number and proportions of persons active in different branches of sports based on indirect data. I compared the size of the membership of the separate sports associations and the number of participants in the Estonian championships of the three largest sports games (football, basketball, volleyball). Periodicals proved to be the most reliable in ascertaining the numbers of spectators since they unfailingly noted the larger attendance numbers based on spectator ticket information or visual observation. The sketchy information on attendance at competitions in individual sports is a problem, but from the standpoint of this article’s research problem, the fact that before World War II there was not a single large sports arena in Estonia is important. The gymnasiums that were in use accommodated slightly over 500 spectators in total. This means that a thousand and more spectators could gather only at stadiums, where primarily football matches and track and field competitions were held. The print media reported the numbers of spectators at those competitions. I compared the attendance numbers for football and track and field competitions, and calculated the average number of spectators. There are gaps in the balance sheets and revenue reports of the separate sports associations for the period under consideration, yet the Eesti Spordi Keskliit (Central Association of Estonian Sports) published them in its yearbooks for 1935–1939, which makes it possible to draw correct conclusions concerning the economic viability of the separate sports associations. While I used the method of source criticism for the preceding three categories, I studied the representation of branches of sports in print media together with Kristjan Remmelkoor using content analysis. We focused exclusively on print media because that was the primary means of mass communication at that time, and it covered the entire period under consideration, unlike radio, which began broadcasting for the first time in 1926. On the basis of circulation numbers, we selected two dailies with nationwide circulation that were published in Tallinn (Vaba Maa was published only until 1938, thus it was replaced for final comparison with another Tallinn daily paper Uus Eesti) and one daily from southern Estonia for content analysis. We studied the newspaper issues from the years 1921, 1925, 1930, 1935 and 1939. Based on the pilot project, we identified the branches of sports that were reported the most and worked out a methodology on the basis of which to search for and categorise branches of sports. After six months, I carried out a repeat analysis for one month of each year that was under consideration. The repeat analysis covered all four dailies. The results differed by 3.97%. Thereat in comparing the two branches of sports that were reported on most, the difference in football was 0.69% and 0.43% in track and field. It became evident as a result of the study that compared to basketball and volleyball, there were almost four times more football enthusiasts. Compared to the other more popular individual sports, we can indirectly conclude that football was the branch of sports with the largest number of enthusiasts. Football had the most spectators in Estonia in the interwar period because branches of sports practiced in indoor conditions could not fit more than 500 spectators into gymnasiums, since there was no large sports arena. Football had the largest audiences when considering the track and field competitions and football matches held at stadiums. In 1935–1939, the Eesti Jalgpalli Liit (Estonian Football Association) was Estonia’s most prosperous separate sports association. It became evident on the basis of content analysis that the two most widely reported branches of sports in print media were football, and track and field. Thereat the number of reports on track and field grew in the latter half of the 1930s and surpassed the figures for football. At the same time, the number of texts on Estonian football was the largest over the entire period that has been studied. The greatest number of texts on football were in journalistic genres that required absorbed reading, which stood out better in newspapers. Due to these circumstances, football became the most popular branch of sports in Estonia in the interwar period. The Estonian national squad’s international match against Latvia held on 18 June 1940 characterises football’s symbolic capital. This match that took place at Kadriorg stadium at a turning point in history evolved into a nationalist demonstration against the Soviet Union’s occupying regime. The crowd went from the stadium to Kadriorg Palace, where President Konstantin Päts was under the guard of the foreign regime. This match and the events that followed it are etched in the people’s collective memory. They have made their way into many published memoirs and also into belles-lettres, and have been echoed in both poetry and prose.

Synthetic protocols for the palladium-catalyzed arylation of various linear and cyclic polyamines and polyoxapolyamines has been worked out. Pd(0) and Pd(II)complexes with such phosphine ligands as dppf, BINAP, PPF-OMe, P(tBu)3,2-ditert-butylphosphino-1,1'-biphenyl have been explored in the catalytic amination reactions. Monoamination of chloro-, bromo-, and iodoarenes with di-, tri-, and tetraamines have been carried out, conditions for di- and polyarylation of linear polyamines have been elaborated. Successful arylation of 1,4,7,10-tetraazacyclododecane (cyclene) and 1,4,8,11-tetraazacyclotetradecane (cyclam) have been conducted. Intramolecular diamination of dihaloarenes such as 1,2-dibromobenzene, 2,6-dichlorobromobenzene, 1,3-dibromobenzene, 1,8-dichloroanthracene, 1,8-dichloroanthraquinone, 1,5-dichloroanthracene, and 1,5-dichloroanthraquinone afforded corresponding polyazamacrocycles containing arene moieties. For the first time, a convenient one-pot synthesis of the face-to-face arranged bismacrocyclic systems has been carried out.

Under standard laboratory conditions of rectangular light/dark cycles and constant warm temperature, Drosophila melanogaster show bursts of morning (M) and evening (E) locomotor activity and a “siesta” in the middle of the day. These M and E components have been critical for developing the neuronal dual oscillator model in which clock gene expression in key cells generates the circadian phenotype. However, under natural European summer conditions of cycling temperature and light intensity, an additional prominent afternoon (A) component that replaces the siesta is observed. This component has been described as an “artifact” of the TriKinetics locomotor monitoring system that is used by many circadian laboratories world wide. Using video recordings, we show that the A component is not an artifact, neither in the glass tubes used in TriKinetics monitors nor in open-field arenas. By studying various mutants in the visual and peripheral and internal thermo-sensitive pathways, we reveal that the M component is predominantly dependent on visual input, whereas the A component requires the internal thermo-sensitive channel transient receptor potential A1 (TrpA1). Knockdown of TrpA1 in different neuronal groups reveals that the reported expression of TrpA1 in clock neurons is unlikely to be involved in generating the summer locomotor profile, suggesting that other TrpA1 neurons are responsible for the A component. Studies of circadian rhythms under seminatural conditions therefore provide additional insights into the molecular basis of circadian entrainment that would otherwise be lost under the usual standard laboratory protocols.

The article discusses the development of complex items that may carry grammatical as well as pragmatic functions. We describe the development of the Estonian complex conjunction nii et ‘so that’ which started out as the free combination of the proadverb nii ‘so’ and the conjunction et ‘that’, and has currently reached the stage of pragmatic marker located at the sentence-peripheral position and expressing CONCLUSION. The synchronic corpus study analyzes 862 examples and observes the functional and the formal variation of nii et ‘so that’, ‘so’ as well as the association between them. The data suggests that nii et has four formal variants (nii, et; nii et; niiet; niet) and its functions have developed in the following chain: MANNER > CONSEQUENCE > CONCLUSION. The data suggest an association between the functional and formal variation. The development of nii et displays the main mechanisms of grammaticalization (desemanticization, decategorialization, extension, erosion) and is associated with re-cycling of grammar, and pragmatic roles of sentence peripheries.Kokkuvõte. Anni Jürine ja Külli Habicht: Liitsete üksuste grammatiseerumine: eesti keele nii et. Artiklis käsitletakse liitüksuste grammatiseerumist (pragmatiseerumist) eesti ühendsidesõna nii et näitel. See algselt eri lauseosadesse kuulunud sidendav üksus on reanalüüsitud esmalt alistatud osalauset alustavaks ühendsidesõnaks ja lõpuks lause perifeeriatesse paiknevaks pragmaatiliseks partikliks. Sünkroonilises korpusuuringus analüüsitakse 862 kasutusjuhtu ning selgitatakse välja vormi ja funktsiooni seosed grammatiseerumisprotsessis. Üksusel on neli vormivarianti (nii, et; nii et; niiet; niet) ja tema funktsioonid on kujunenud ahelas VIIS > TAGAJÄRG > JÄRELDUS. Üksuse areng järgib grammatiseerumise keskseid mehhanisme (desemantiseerumine, dekategoriseerumine, ekstensioon, erosioon) ja on seotud grammatika taaskasutuse, insubordinatsiooni ning lause perifeeriate pragmaatiliste rollidega.Võtmesõnad: liitne grammatikaüksus; pragmaatiline partikkel; grammatiseerumine; pragmatiseerumine; grammatika taaskasutus; lause perifeeriad; insubordinatsioon; eesti keel

Abstract Background The twin problems of severe alcohol dependence and homelessness are associated with precarious living and multiple acute, social and chronic harms. While much attention has been focused on harm reduction services for illicit drug use, there has been less attention to harm reduction for this group. Managed alcohol programs (MAPs) are harm reduction interventions that aim to reduce the harms of severe alcohol use, poverty and homelessness. MAPs typically provide accommodation, health and social supports alongside regularly administered sources of beverage alcohol to stabilize drinking patterns and replace use of non-beverage alcohol (NBA). Methods We examined impacts of MAPs in reducing harms and risks associated with substance use and homelessness. Using case study methodology, data were collected from five MAPs in five Canadian cities with each program constituting a case. In total, 53 program participants, 4 past participants and 50 program staff were interviewed. We used situational analysis to produce a series of “messy”, “ordered” and “social arenas” maps that provide insight into the social worlds of participants and the impact of MAPs. Results Prior to entering a MAP, participants were often in a revolving world of cycling through multiple arenas (health, justice, housing and shelters) where abstinence from alcohol is often required in order to receive assistance. Residents described living in a street-based survival world characterized by criminalization, unmet health needs, stigma and unsafe spaces for drinking and a world punctuated by multiple losses and disconnections. MAPs disrupt these patterns by providing a harm reduction world in which obtaining accommodation and supports are not contingent on sobriety. MAPs represent a new arena that focuses on reducing harms through provision of safer spaces and supply of alcohol, with opportunities for reconnection with family and friends and for Indigenous participants, Indigenous traditions and cultures. Thus, MAPs are safer spaces but also potentially spaces for healing. Conclusions In a landscape of limited alcohol harm reduction options, MAPs create a new arena for people experiencing severe alcohol dependence and homelessness. While MAPs reduce precarity for participants, programs themselves remain precarious due to ongoing challenges related to lack of understanding of alcohol harm reduction and insecure program funding.

Abstract Promotion of tourism that simultaneously surge in various regions in Indonesia is currently experiencing quite encouraging developments. Indonesia's tourism potential, which is largely a marine potential, encourages local governments to manage it so that it can become an icon of the region in the world arena. Sports tourism activities are now a strategy of local governments to build their region. Like the international cycling race in Ambon that encourages the acceleration of the construction of roads that become the means of competition, as well as build a connecting road to the remote areas. Today International fishing events are also the trigger of development to remote areas. This is done by North Maluku Provincial Government through the international fishing contest, Widi International Fishing Tournament 2017 (WIFT) 2017. The event held in Widi Islands, South Halmahera Regency took place on 25-29 October 2017, is expected to become a prestigious international competition for trophies president of RI. The research method used descriptive qualitative method by evaluating marketing mix principles (marketing mix). The results revealed that the preparation (planning) is the key to success of an area in organizing a sport tourism event. In communication studies, tourism promotion can be seen as practice / implementation of local government strategy in forming image / image of an organization (government). The results revealed that promotional activities and publications at the level of government conducted by Disparpor Halsel Regency has not run optimally. However, thanks to the collaboration with all stakeholders, this event can take place orderly and smoothly. This inaugural event can be quite successful. However, with all the limitations that exist, this event has proved that marine tourism Indonesia has ogled international tourists .. this is the image / image that has been successfully built properly. Keyword: Communication tourism, Marketing Mix, WIFT 2017.

ABSTRACTA bending beam technique was used to measure the mechanical stresses in AlSi(l%)Cu(0.5%) blanket films as well as in patterned lines (aspect ratio: 0.8) - unpassivated and passivated with SiNx - during thermal cycling from –170°C or room temperature to 450°C.Main results are:a) No significant differences in unpassivated and passivated blanket films with thickness ranging from 0.2 µm to 3.2 µm.b) In unpassivated patterned lines of 0.8 µm thickness the stresses across the lines are very small, while parallel to the lines they show nearly elastic behaviour, except at high temperatures.c) In passivated patterned lines the stresses are much higher than in blanket films, very similar parallel and across the line and nearly elastic. The stress relaxation is small compared with blanket films and depends strongly on the temperature.

Development of new therapeutic strategies for breast cancer is urgently needed due to the sustained emergence of drug resistance, tumor recurrence and metastasis. To gain a novel insight into therapeutic approaches to fight against breast cancer, the cytocidal effects of hellebrigenin (Helle) and arenobufagin (Areno) were investigated in human estrogen receptor (ER)-positive breast cancer cell line MCF-7 and triple-negative breast cancer cell line MDA-MB-231. Helle exhibited more potent cytotoxicity than Areno in both cancer cells, and MCF-7 cells were more susceptible to both drugs in comparison with MDA-MB-231 cells. Apoptotic-like morphological characteristics, along with the downregulation of the expression level of Bcl-2 and Bcl-xL and the upregulation of the expression level of Bad, were observed in Helle-treated MCF-7 cells. Helle also caused the activation of caspase-8, caspase-9, along with the cleavage of poly(ADP-ribose) polymerase in MCF-7 cells. Helle-mediated necrosis-like phenotype, as evidenced by the increased propidium iodide (PI)-positive cells was further observed. G2/M cell cycle arrest was also induced by Helle in the cells. Upregulation of the expression level of p21 and downregulation of the expression level of cyclin D1, cyclin E1, cdc25C and survivin were observed in MCF-7 cells treated with Helle and occurred in parallel with G2/M arrest. Autophagy was triggered in MCF-7 cells and the addition of wortmannin or 3-MA, two well-known autophagy inhibitors, slightly but significantly rescued the cells. Furthermore, similar alterations of some key molecules associated with the aforementioned biological phenomena were observed in MDA-MB-231 cells. Intriguingly, the numbers of PI-positive cells in Helle-treated MCF-7 cells were significantly reduced by wortmannin and 3-MA, respectively. In addition, Helle-triggered G2/M arrest was significantly corrected by wortmannin, suggesting autophagy induction contributed to Helle-induced cytotoxicity of breast cancer cells by modulating necrosis and cell cycle arrest. Collectively, our results suggested potential usefulness of both Helle and Areno in developing therapeutic strategies to treat patients with different types of breast cancer, especially ER-positive breast cancer.

As the single most successful social-networking Website to date, Facebook has caused a shift in both practice and perception of online socialisation, and its relationship to the offline world. While not the first online social networking service, Facebook’s user base dwarfs its nearest competitors. Mark Zuckerberg’s creation boasts more than 750 million users (Facebook). The currently ailing MySpace claimed a ceiling of 100 million users in 2006 (Cashmore). Further, the accuracy of this number has been contested due to a high proportion of fake or inactive accounts. Facebook by contrast, claims 50% of its user base logs in at least once a day (Facebook). The popular and mainstream uptake of Facebook has shifted social use of the Internet from various and fragmented niche groups towards a common hub or portal around which much everyday Internet use is centred. The implications are many, but this paper will focus on the progress what Mimi Marinucci terms the “Facebook effect” (70) and the evolution of lists as a filtering mechanism representing one’s social zones within Facebook. This is in part inspired by the launch of Google’s new social networking service Google+ which includes “circles” as a fundamental design feature for sorting contacts. Circles are an acknowledgement of the shortcomings of a single, unified friends list that defines the Facebook experience. These lists and circles are both manifestations of the same essential concept: our social lives are, in fact, divided into various zones not defined by an online/offline dichotomy, by fantasy role-play, deviant sexual practices, or other marginal or minority interests. What the lists and circles demonstrate is that even very common, mainstream people occupy different roles in everyday life, and that to be effective social tools, social networking sites must grant users control over their various identities and over who knows what about them. Even so, the very nature of computer-based social tools lead to problematic definitions of identities and relationships using discreet terms, in contrast to more fluid, performative constructions of an individual and their relations to others. Building the Monolith In 1995, Sherry Turkle wrote that “the Internet has become a significant social laboratory for experimenting with the constructions and reconstructions of self that characterize postmodern life” (180). Turkle describes the various deliberate acts of personnae creation possible online in contrast to earlier constraints placed upon the “cycling through different identities” (179). In the past, Turkle argues, “lifelong involvement with families and communities kept such cycling through under fairly stringent control” (180). In effect, Turkle was documenting the proliferation of identity games early adopters of Internet technologies played through various means. Much of what Turkle focused on were MUDs (Multi-User Dungeons) and MOOs (MUD Object Oriented), explicit play-spaces that encouraged identity-play of various kinds. Her contemporary Howard Rheingold focused on what may be described as the more “true to life” communities of the WELL (Whole Earth ‘Lectronic Link) (1–38). In particular, Rheingold explored a community established around the shared experience of parenting, especially of young children. While that community was not explicitly built on the notion of role-play, the parental identity was an important quality of community members. Unlike contemporary social media networks, these early communities were built on discreet platforms. MUDs, MOOs, Bulletin Board Systems, UseNet Groups and other early Internet communication platforms were generally hosted independently of one another, and even had to be dialled into via modem separately in some cases (such as the WELL). The Internet was a truly disparate entity in 1995. The discreetness of each community supported the cordoning off of individual roles or identities between them. Thus, an individual could quite easily be “Pete” a member of the parental WELL group and “Gorak the Destroyer,” a role-player on a fantasy MUD without the two roles ever being associated with each other. As Turkle points out, even within each MUD ample opportunity existed to play multiple characters (183–192). With only a screen name and associated description to identify an individual within the MUD environment, nothing technical existed to connect one player’s multiple identities, even within the same community. As the Internet has matured, however, the tendency has been shifting towards monolithic hubs, a notion of collecting all of “the Internet” together. From a purely technical and operational perspective, this has led to the emergence of the ISP (Internet service provider). Users can make a connection to one point, and then be connected to everything “on the Net” instead of individually dialling into servers and services one at a time as was the case in the early 1980s with companies such as Prodigy, the Source, CompuServe, and America On-Line (AOL). The early information service providers were largely walled gardens. A CompuServe user could only access information on the CompuServe network. Eventually the Internet became the network of choice and services migrated to it. Standards such as HTTP for Web page delivery and SMTP for email became established and dominate the Internet today. Technically, this has made the Internet much easier to use. The services that have developed on this more rationalised and unified platform have also tended toward monolithic, centralised architectures, despite the Internet’s apparent fundamental lack of a hierarchy. As the Internet replaced the closed networks, the wider Web of HTTP pages, forums, mailing lists and other forms of Internet communication and community thrived. Perhaps they required slightly more technological savvy than the carefully designed experience of walled-garden ISPs such as AOL, but these fora and IRC (Internet Relay Chat) rooms still provided the discreet environments within which to role-play. An individual could hold dozens of login names to as many different communities. These various niches could be simply hobby sites and forums where a user would deploy their identity as model train enthusiast, musician, or pet owner. They could also be explicitly about role-play, continuing the tradition of MUDs and MOOs into the new millennium. Pseudo- and polynymity were still very much part of the Internet experience. Even into the early parts of the so-called Web 2.0 explosion of more interactive Websites which allowed for easier dialog between site owner and viewer, a given identity would be very much tied to a single site, blog or even individual comments. There was no “single sign on” to link my thread from a music forum to the comments I made on a videogame blog to my aquarium photos at an image gallery site. Today, Facebook and Google, among others, seek to change all that. The Facebook Effect Working from a psychological background Turkle explored the multiplicity of online identities as a valuable learning, even therapeutic, experience. She assessed the experiences of individuals who were coming to terms with aspects of their own personalities, from simple shyness to exploring their sexuality. In “You Can’t Front on Facebook,” Mimi Marinucci summarizes an analysis of online behaviour by another psychologist, John Suler (67–70). Suler observed an “online disinhibition effect” characterised by users’ tendency to express themselves more openly online than offline (321). Awareness of this effect was drawn (no pun intended) into popular culture by cartoonist Mike Krahulik’s protagonist John Gabriel. Although Krahulik’s summation is straight to the point, Suler offers a more considered explanation. There are six general reasons for the online disinhibition effect: being anonymous, being invisible, the communications being out of sync, the strange sensation that a virtual interlocutor is all in the mind of the user, the general sense that the online world simply is not real and the minimisation of status and authority (321–325). Of the six, the notion of anonymity is most problematic, as briefly explored above in the case of AOL. The role of pseudonymity has been explored in more detail in Ruch, and will be considered with regard to Facebook and Google+ below. The Facebook effect, Marinucci argues, mitigates all six of these issues. Though Marinucci explains the mitigation of each factor individually, her final conclusion is the most compelling reason: “Facebook often facilitates what is best described as an integration of identities, and this integration of identities in turn functions as something of an inhibiting factor” (73). Ruch identifies this phenomenon as the “aggregation of identities” (219). Similarly, Brady Robards observes that “social network sites such as MySpace and Facebook collapse the entire array of social relationships into just one category, that of ‘Friend’” (20). Unlike earlier community sites, Ruch notes “Facebook rejects both the mythical anonymity of the Internet, but also the actual pseudo- or polynonymous potential of the technologies” (219). Essentially, Facebook works to bring the offline social world online, along with all the conventional baggage that accompanies the individual’s real-world social life. Facebook, and now Google+, present a hard, dichotomous approach to online identity: anonymous and authentic. Their socially networked individual is the “real” one, using a person’s given name, and bringing all (or as many as the sites can capture) their contacts from the offline world into the online one, regardless of context. The Facebook experience is one of “friending” everyone one has any social contact with into one homogeneous group. Not only is Facebook avoiding the multiple online identities that interested Turkle, but it is disregarding any multiplicity of identity anywhere, including any online/offline split. David Kirkpatrick reports Mark Zuckerberg’s rejection of this construction of identity is explained by his belief that “You have one identity … having two identities for yourself is an example of a lack of integrity” (199). Arguably, Zuckerberg’s calls for accountability through identity continue a perennial concern for anonymity online fuelled by “on the Internet no one knows you’re a dog” style moral panics. Over two decades ago Lindsy Van Gelder recounted the now infamous case of “Joan and Alex” (533) and Julian Dibbell recounted “a rape in cyberspace” (11). More recent anxieties concern the hacking escapades of Anonymous and LulzSec. Zuckerberg’s approach has been criticised by Christopher Poole, the founder of 4Chan—a bastion of Internet anonymity. During his keynote presentation at South by SouthWest 2011 Poole argued that Zuckerberg “equates anonymity with a lack of authenticity, almost a cowardice.” Yet in spite of these objections, Facebook has mainstream appeal. From a social constructivist perspective, this approach to identity would be satisfying the (perceived?) need for a mainstream, context-free, general social space online to cater for the hundreds of millions of people who now use the Internet. There is no specific, pre-defined reason to join Facebook in the way there is a particular reason to join a heavy metal music message board. Facebook is catering to the need to bring “real” social life online generally, with “real” in this case meaning “offline and pre-existing.” Very real risks of missing “real life” social events (engagements, new babies, party invitations etc) that were shared primarily via Facebook became salient to large groups of individuals not consciously concerned with some particular facet of identity performance. The commercial imperatives towards monolithic Internet and identity are obvious. Given that both Facebook and Google+ are in the business of facilitating the sale of advertising, their core business value is the demographic information they can sell to various companies for target advertising. Knowing a user’s individual identity and tastes is extremely important to those in the business of selling consumers what they currently want as well as predicting their future desires. The problem with this is the dawning realisation that even for the average person, role-playing is part of everyday life. We simply aren’t the same person in all contexts. None of the roles we play need to be particularly scandalous for this to be true, but we have different comfort zones with people that are fuelled by context. Suler proposes and Marinucci confirms that inhibition may be just as much part of our authentic self as the uninhibited expression experienced in more anonymous circumstances. Further, different contexts will inform what we inhibit and what we express. It is not as though there is a simple binary between two different groups and two different personal characteristics to oscillate between. The inhibited personnae one occupies at one’s grandmother’s home is a different inhibited self one plays at a job interview or in a heated discussion with faculty members at a university. One is politeness, the second professionalism, the third scholarly—yet they all restrain the individual in different ways. The Importance of Control over Circles Google+ is Google’s latest foray into the social networking arena. Its previous ventures Orkut and Google Buzz did not fare well, both were variously marred by legal issues concerning privacy, security, SPAM and hate groups. Buzz in particular fell afoul of associating Google accounts with users” real life identities, and (as noted earlier), all the baggage that comes with it. “One user blogged about how Buzz automatically added her abusive ex-boyfriend as a follower and exposed her communications with a current partner to him. Other bloggers commented that repressive governments in countries such as China or Iran could use Buzz to expose dissidents” (Novak). Google+ takes a different approach to its predecessors and its main rival, Facebook. Facebook allows for the organisation of “friends” into lists. Individuals can span more than one list. This is an exercise analogous to what Erving Goffman refers to as “audience segregation” (139). According to the site’s own statistics the average Facebook user has 130 friends, we anticipate it would be time-consuming to organise one’s friends according to real life social contexts. Yet without such organisation, Facebook overlooks the social structures and concomitant behaviours inherent in everyday life. Even broad groups offer little assistance. For example, an academic’s “Work People” list may include the Head of Department as well as numerous other lecturers with whom a workspace is shared. There are things one might share with immediate colleagues that should not be shared with the Head of Department. As Goffman states, “when audience segregation fails and an outsider happens upon a performance that was not meant for him, difficult problems in impression management arise” (139). By homogenising “friends” and social contexts users are either inhibited or run the risk of some future awkward encounters. Google+ utilises “circles” as its method for organising contacts. The graphical user interface is intuitive, facilitated by an easy drag and drop function. Use of “circles” already exists in the vocabulary used to describe our social structures. “List” by contrast reduces the subject matter to simple data. The utility of Facebook’s friends lists is hindered by usability issues—an unintuitive and convoluted process that was added to Facebook well after its launch, perhaps a reaction to privacy concerns rather than a genuine attempt to emulate social organisation. For a cogent breakdown of these technical and design problems see Augusto Sellhorn. Organising friends into lists is a function offered by Facebook, but Google+ takes a different approach: organising friends in circles is a central feature; the whole experience is centred around attempting to mirror the social relations of real life. Google’s promotional video explains the centrality of emulating “real life relationships” (Google). Effectively, Facebook and Google+ have adopted two different systemic approaches to dealing with the same issue. Facebook places the burden of organising a homogeneous mass of “friends” into lists on the user as an afterthought of connecting with another user. In contrast, Google+ builds organisation into the act of connecting. Whilst Google+’s approach is more intuitive and designed to facilitate social networking that more accurately reflects how real life social relationships are structured, it suffers from forcing direct correlation between an account and the account holder. That is, use of Google+ mandates bringing online the offline. Google+ operates a real names policy and on the weekend of 23 July 2011 suspended a number of accounts for violation of Google’s Community Standards. A suspension notice posted by Violet Blue reads: “After reviewing your profile, we determined the name you provided violates our Community Standards.” Open Source technologist Kirrily Robert polled 119 Google+ users about their experiences with the real names policy. The results posted to her on blog reveal that users desire pseudonymity, many for reasons of privacy and/or safety rather than the lack of integrity thought by Zuckerberg. boyd argues that Google’s real names policy is an abuse of power and poses danger to those users employing “nicks” for reasons including being a government employment or the victim of stalking, rape or domestic abuse. A comprehensive list of those at risk has been posted to the Geek Feminism Wiki (ironically, the Wiki utilises “Connect”, Facebook’s attempt at a single sign on solution for the Web that connects users’ movements with their Facebook profile). Facebook has a culture of real names stemming from its early adopters drawn from trusted communities, and this culture became a norm for that service (boyd). But as boyd also points out, “[r]eal names are by no means universal on Facebook.” Google+ demands real names, a demand justified by rhetoric of designing a social networking system that is more like real life. “Real”, in this case, is represented by one’s given name—irrespective of the authenticity of one’s pseudonym or the complications and dangers of using one’s given name. Conclusion There is a multiplicity of issues concerning social networks and identities, privacy and safety. This paper has outlined the challenges involved in moving real life to the online environment and the contests in trying to designate zones of social context. Where some earlier research into the social Internet has had a positive (even utopian) feel, the contemporary Internet is increasingly influenced by powerful and competing corporations. As a result, the experience of the Internet is not necessarily as flexible as Turkle or Rheingold might have envisioned. Rather than conducting identity experimentation or exercising multiple personnae, we are increasingly obligated to perform identity as it is defined by the monolithic service providers such as Facebook and Google+. This is not purely an indictment of Facebook or Google’s corporate drive, though they are obviously implicated, but has as much to do with the new social practice of “being online.” So, while there are myriad benefits to participating in this new social context, as Poole noted, the “cost of failure is really high when you’re contributing as yourself.” Areas for further exploration include the implications of Facebook positioning itself as a general-purpose user authentication tool whereby users can log into a wide array of Websites using their Facebook credentials. If Google were to take a similar action the implications would be even more convoluted, given the range of other services Google offers, from GMail to the Google Checkout payment service. 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