PEGylation of lysine residues reduces the pro-migratory activity of IGF-I

Background: The insulin-like growth factor (IGF) system is composed of ligands and receptors which regulate cell proliferation, survival, differentiation and migration. Some functions are regulated via intracellular signaling cascades, others by involvement of the extracellular milieu, including binding proteins and other extracellular matrix proteins. However, understanding of their functions and the exact nature of these interactions remains incomplete. Methods: IGF-I was PEGylated at its lysine sites - K27, K65 and K68. Binding of PEG-IGF-I to the IGFBPs was analyzed using BIAcore and its ability to activate the IGF-IR was assessed using IGF-IR phosphorylation assay. Furthermore, functional consequences of PEGylating the lysine residues of IGF-I was investigated using cell viability and cell migration assays. In addition, particular downstream signaling pathways regularly implicated in these mechanisms were also dissected using phospho-AKT and phospho-ERK1/2 assays. Results: In this study, IGF-I specifically PEGylated at lysine 27 (PEG-K27), 65 (PEG-K65) or 68 (PEG-K68) were employed. Receptor phosphorylation was only reduced by 2-fold with PEG-K65 and PEG-K68 over all the time points tested, and as observed in two cell types, 3T3 fibroblasts and MCF-7 breast cancer cells. PEGylation at K27 resulted in a much larger effect, with more than 10-fold lower activation for 3T3 fibroblasts and a ~3 fold reduced IGF-IR activation for MCF-7 breast cancer cells over 15 minutes. In addition, all PEG-IGF-I variants demonstrated a ten-fold reduction in the association rate to IGF binding proteins (IGFBPs). Functionally, all PEG variants completely lost their ability to induce cell migration in the presence of IGFBP-3/vitronectin (VN) complexes as compared to IGF-I; in contrast, cell viability was fully preserved. Further investigations into the downstream signaling pathways revealed that the PI3-K/AKT pathway was preferentially affected upon treatment with the PEG-IGF-I variants compared to the MAPK/ERK pathway. Conclusion: PEGylation of IGF-I has an impact on cell migration but not cell viability. General significance: PEG-IGF-I may differentially modulate IGF-I mediated functions that are dependent on its interaction with its receptor as well as key extracellular proteins such as VN and IGFBPs.

The nature and correlates of young women's peer-directed protective behavioral strategies

Objective Recently, a number of studies have identified self-employed Protective Behavioral Strategies (PBS) as effective in decreasing the level of alcohol-related harm among young people. However, much of the published research has ignored important gender differences, such as women's increased tendency to rely on PBS that are social in nature. To further the understanding of women's PBS, the current study sought to investigate the nature and correlates of the strategies young women employ to keep their friends safe when drinking (i.e., peer-directed PBS). Method A scale measuring peer-directed PBS was developed and administered in conjunction with existing measures of alcohol consumption, personal PBS, and peer attachment. Participants consisted of 422 women aged 18–30 years, recruited among psychology students and the general public. Results Exploratory factor analysis revealed two clusters of peer-directed PBS; those that were aimed at reducing intoxication among one's friends and those that were designed to minimize alcohol-related harms. Further analysis found a positive relationship between women's tendency to implement personal and peer-directed PBS and that risky drinkers were less likely to engage in personal or peer-directed PBS (either type). Conclusion Findings indicate that personal and peer-directed PBS are related behaviors that are less frequently adopted by risky drinkers.

Generalized aggregate Quality of Service computation for composite services

This article addresses the problem of estimating the Quality of Service (QoS) of a composite service given the QoS of the services participating in the composition. Previous solutions to this problem impose restrictions on the topology of the orchestration models, limiting their applicability to well-structured orchestration models for example. This article lifts these restrictions by proposing a method for aggregate QoS computation that deals with more general types of unstructured orchestration models. The applicability and scalability of the proposed method are validated using a collection of models from industrial practice.

Finite-SNR diversity-multiplexing trade-off of inter-vehicular cooperative diversity protocols

The finite-signal-to-noise ratio (SNR) diversity-multiplexing trade-off (DMT) of cooperative diversity protocols are investigated in vehicular networks based on cascaded Rayleigh fading. Lower bounds of DMT at finite SNR for orthogonal and non-orthogonal protocols are derived. The results showcase the first look into the achievable DMT trade-off of cooperative diversity in volatile vehicular environments. It is shown that the diversity gains are significantly suboptimal at realistic SNRs.

Penal Colonies

Prostitution has been closely associated with the transportation of women convicts to British penal colonies. Convict labor was used to found a number of British colonies including Barbados, Jamaica, Maryland, Virginia, Singapore, New South Wales, Tasmania, and Western Australia. Between 1607 and 1939, Britain transported approximately 400,000 convicts, 162,000 of whom came to Australia and about 50,000 to North America. Significant numbers of women were among those transported to the Australian and North American colonies, although their numbers were relatively small in comparison to male convicts. Transportation was typically reserved for the most recalcitrant of female offenders. Most women transported came from working-class populations, resided in metropolitan centers, and were single at the time of their offense. Although few of these women were actually sentenced for activities associated with prostitution, large numbers had a history of involvement with prostitution. Transportation was considered to offer prostitutes a chance at redemption, with colonial commentators drawing contrasts between the Old World and its vice-ridden sensuality and the colonies, which offered opportunities for redemption through religious devotion and hard work. Many women transported to the Australian colonies were described by officials as being "on the town" at their time of apprehension and were collectively considered to be "damned whores, possessed of neither virtue nor honesty". Recently, historians have argued that these assessments were emblematic of middle-class prejudices toward the open and aggressive sexuality of working-class women. The number of convict women involved in prostitution may have been higher than recorded crimes, typically involving "larceny", suggest. A number of women were charged with theft from men who had paid them (or, in some instances, refused to pay them) for sex. Historians have estimated that one in five convict women were part-time or full-time prostitutes before transportation. Many continued in prostitution after transportation, with prostitution becoming an important element in the social and economic life of the Australian colonies, where, between 1788-1830, men outnumbered women six to one. Officially, prostitution was tolerated to dissuade men from vice. For women, prostitution presented a means of securing physical protection and accommodation at a time when general amenities and employment opportunities were restricted.

Importance of knowledge management processes in a project-based organization : a case study of research enterprise

Knowledge Management (KM) is vital factor to successfully undertake projects. The temporary nature of projects necessitates employing useful KM practices for tackling issues such as knowledge leakiness and rework. The Project Management Office (PMO) is a unit within organizations to facilitate and oversee organizational projects. Project Management Maturity Models (PMMM) shows the development of PMOs from immature to mature levels. The existing PMMMs have focused on discussing Project Management (PM) practices, however, the management of project knowledge is yet to be addressed, at various levels of maturity. This research project was undertaken to investigate the mentioned gap for addressing KM practices at the existing PMMMs. Due to the exploratory and inductive nature of this research, qualitative methods were chosen as the research methodology. In total, three cases selected from different industries: research; mining and government organizations, to provide broad categories for research and research questions were examined using the developed framework. This paper presents the partial findings of undertaken investigation of the research organisation with the lowest level of maturity. The result shows that knowledge creation and capturing are the most important processes, while knowledge transferring and reusing are not as important as the other two processes. In addition, it was revealed that provision of “knowledge about client” and “project management knowledge” are the most important types of knowledge that are required at this level of maturity. In conclusion, the outcomes of this paper shall provide powerful guidance to PMOs at lowest level of maturity from KM point of view.

Children's Literature Digital Resources Project

Children's Literature Digital Resources is a full text digital repository of Australian children’s literature from 1830 to 1945. Users can read online the complete texts of a selection of early Australian children’s literature, both popular and rare. Digitised items include children’s and young adult fiction, poetry, short stories, and picture books. Users can also read related full text critical articles that were digitised as part of the project.

The psychosocial purpose of driving and its relationship with the risky driving behaviour of young novice drivers

Background The overrepresentation of young drivers in road crashes, injuries and fatalities around the world has resulted in a breadth of injury prevention efforts including education, enforcement, engineering, and exposure control. Despite multifaceted intervention, the young driver problem remains a challenge for injury prevention researchers, practitioners and policy-makers. The intractable nature of young driver crash risks suggests that a deeper understanding of their car use – that is, the purpose of their driving – is required to inform the design of more effective young driver countermeasures. Aims This research examined the driving purpose reported by young drivers, including the relationship with self-reported risky driving behaviours including offences. Methods Young drivers with a Learner or Provisional licence participated in three online surveys (N1 = 656, 17–20 years; N2 = 1051, 17–20 years; N3 = 351, 17–21 years) as part of a larger state-wide project in Queensland, Australia. Results A driving purpose scale was developed (the PsychoSocial Purpose Driving Scale, PSPDS), revealing that young drivers drove for psychosocial reasons such as for a sense of freedom and to feel independent. Drivers who reported the greatest psychosocial purpose for driving were more likely to be male and to report more risky driving behaviours such as speeding. Drivers who deliberately avoided on-road police presence and reported a prior driving-related offence had significantly greater PSPDS scores, and higher reporting of psychosocial driving purposes was found over time as drivers transitioned from the supervised Learner licence phase to the independent Provisional (intermediate) licence phase. Discussion and conclusions The psychosocial needs met by driving suggest that effective intervention to prevent young driver injury requires further consideration of their driving purpose. Enforcement, education, and engineering efforts which consider the psychosocial purpose of the driving are likely to be more efficacious than those which presently do not. Road safety countermeasures could reduce the young driver’s exposure to risk through such mechanisms as encouraging the use of public transport.

Diagnosing adult Attention Deficit Hyperactivity Disorder: Are late onset and subthreshold ciagnoses valid?

Objective Diagnosing attention deficit hyperactivity disorder (ADHD) in adults is difficult when diagnosticians cannot establish an onset before the DSM-IV criterion of age 7 or if the number of symptoms recalled does not achieve DSM’s diagnosis threshold. Method The authors addressed the validity of DSM-IV’s age-at-onset and symptom threshold criteria by comparing four groups of adults: 127 subjects with full ADHD who met all DSM-IV criteria for childhood-onset ADHD, 79 subjects with late-onset ADHD who met all criteria except the age-at-onset criterion, 41 subjects with subthreshold ADHD who did not meet full symptom criteria for ADHD, and 123 subjects without ADHD who did not meet any criteria. The authors hypothesized that subjects with late-onset and subthreshold ADHD would show patterns of psychiatric comorbidity, functional impairment, and familial transmission similar to those seen in subjects with full ADHD. Result Subjects with late-onset and full ADHD had similar patterns of psychiatric comorbidity, functional impairment, and familial transmission. Most children with late onset of ADHD (83%) were younger than 12. Subthreshold ADHD was milder and showed a different pattern of familial transmission than the other forms of ADHD. Conclusions The data about the clinical features of probands and the pattern of transmission of ADHD among relatives found little evidence for the validity of subthreshold ADHD among such subjects, who reported a lifetime history of some symptoms that never met DSM-IV’s threshold for diagnosis. In contrast, the results suggested that late-onset adult ADHD is valid and that DSM-IV’s age-at-onset criterion is too stringent.

Differences in L1 linguistic attention control between monolinguals and bilinguals

Relational elements of language (e.g. spatial prepositions) act to direct attention to aspects of an incoming message. The listener or reader must be able to use these elements to focus and refocus attention on the mental representation being constructed. Research has shown that this type of attention control is specific to language and can be distinguished from attention control for non-relational (semantic or content) elements. Twenty-two monolinguals (18–30 years) and nineteen bilinguals (18–30 years) completed two conditions of an alternating-runs task-switching paradigm in their first language. The relational condition involved processing spatial prepositions, and the non-relational condition involved processing concrete nouns and adjectives. Overall, monolinguals had significantly larger shift costs (i.e. greater attention control burden) in the relational condition than the non-relational condition, whereas bilinguals performed similarly in both conditions. This suggests that proficiency in a second language has a positive impact on linguistic attention control in one's native language.

Kirjan tie lukijalle : Kirjakauppojen vakiintuminen Suomessa 1740 - 1860

Books Paths to Readers describes the history of the origins and consolidation of modern and open book stores in Finland 1740 1860. The thesis approaches the book trade as a part of a print culture. Instead of literary studies choice to concentrate on texts and writers, book history seeks to describe the print culture of a society and how the literary activities and societies interconnect. For book historians, printed works are creations of various individuals and groups: writers, printers, editors, book sellers, censors, critics and finally, readers. They all take part in the creation, delivery and interpretation of printed works. The study reveals the ways selling and distributing books have influenced the printed works and the literary and print culture. The research period 1740 1860 covers the so-called second revolution of the book, or the modernisation of the print culture. The thesis describes the history of 60 book stores and their 96 owners. The study concentrates on three themes: firstly, how the particular book trade network became a central institution for printed works distribution, secondly what were the relations between cosmopolitan European book markets and the national cultural sphere, and thirdly how book stores functioned as cultural institutions and business enterprises. Book stores that have a varied assortment and are targeted to all readers became the main institution for book trade in Finland during 1740 1860. It happened because of three features. First, the book binders monopoly on selling bound copies in Sweden was abolished in 1740s. As a consequence entrepreneurs could concentrate solely to trade activities and offer copies from various publishers at their stores. Secondly the common business model of bartering was replaced by selling copies for cash, first in the German book trade centre Leipzig in 1770s. The change intensified book markets activities and Finnish book stores foreign connections. Thirdly, after Finland was annexed to the Russian empire in 1809, the Grand duchy s administration steered foreign book trade to book stores (because of censorship demands). Up to 1830 s book stores were available only in Helsinki and Turku. During next ten years book stores opened in six regional centres. The early entrepreneurs ran usually vertical businesses consisting of printing, publishing and distribution activities. This strategy lowered costs, eased the delivery of printed works and helped to create elaborated centres for all book activities. These book stores main clientele consisted of the Swedish speaking gentry. During late 1840s various opinion leaders called for the development of a national Finnish print culture, and also book stores. As a result, during the five years before the beginning of the Crimean war (1853 1856) book stores were opened in almost all Finnish towns: at the beginning of the war 36 book stores operated in 21 towns. The later book sellers, mainly functioning in small towns among Finnish speaking people, settled usually strictly for selling activities. Book stores received most of their revenues from selling foreign titles. Swedish, German, French and Belgian (pirate editions of popular French novels) books were widely available for the multilingual gentry. Foreign titles and copies brought in most of the revenues. Censorship inspections or unfavourable custom fees would not limit the imports. Even if the local Finnish print production steadily rose, many copies, even titles, were never delivered via book stores. Only during the 1840 s and 1850 s the most advanced publishers would concentrate on creating publishing programmes and delivering their titles via book stores. Book sellers regulated commissions were small. They got even smaller because of large amounts of unsold copies, various and usual misunderstandings of consignments and accounts or plain accidents that destroyed shipments and warehouses. Also, the cultural aim of a creating large and assortments and the tendency of short selling periods demanded professional entrepreneurship, which many small town book sellers however lacked. In the midst of troublesome business efforts, co-operation and mutual concern of the book market s entrepreneurs were the key elements of the trade, although on local level book sellers would compete, sometimes even ferociously. The difficult circumstances (new censorship decree of 1850, Crimean war) and lack of entrepreneurship, experience and customers meant that half of the book stores opened in 1845 1860 was shut in less than five years. In 1858 the few leading publishers established The Finnish Book Publishers Association. Its first task was to create new business rules and manners for the book trade. The association s activities began to professionalise the whole network, but at the same time the earlier independence of regional publishing and selling enterprises diminished greatly. The consolidation of modern and open book store network in Finland is a history of a slow and complex development without clear signs of a beginning or an end. The ideal book store model was rarely accomplished in its all features. Nevertheless, book stores became the norm of the book trade. They managed to offer larger selections, reached larger clienteles and maintained constant activity better than any other book distribution model. In essential, the book stores methods have not changed up to present times.

"America Would Lose Its Soul" : The Immigration Restriction Debate, 1920-1924

Vuosien 1830 ja 1924 välillä Yhdysvaltoihin muutti noin 35 miljoonaa eurooppalaista. Tämä niinkutsuttu "maahanmuuton vuosisata" päättyi varsin äkillisesti kun Yhdysvallat päätti rajoittaa maahanmuuttoa 1920-luvulla. Vuosina 1921 ja 1924 säädetyt lait asettivat kansallisuuteen perustuvat kiintiöt kaikille eurooppalaisille maahanmuuttajille; vuoden 1924 laki myös lopetti kokonaan japanilaisten maahanmuuton. Tämä työ tutkii näihin kiintiölakeihin johtanutta maahanmuuttajavastaisuuden kasvua sekä etenkin lakien ympärillä käytyä keskustelua. Pääpaino on kongressissa esitetyissä maahanmuuton vastaisissa argumenteissa. Nämä jakautuivat karkeasti ottaen kolmeen kategoriaan: maahanmuuton vastustajat sanoivat, että siirtolaisten vaikutus taloudelliseen tilanteeseen oli epäsuotuisa, siirtolaisten rodullinen ja kulttuurinen "laatu" oli huonontunut, ja siirtolaiset olivat radikaaleja ja bolshevismiin taipuvaisia. Erityistä huolta herätti maahanmuuttajien vaikutus Amerikan kulttuuriseen, rodulliseen ja poliittiseen yhtenäisyyteen. Huoli kansakunnan yhtenäisyydestä oli tulosta paitsi siirtolaisten määrästä myös amerikkalaisessa yhteiskunnassa tapahtuneista muutoksista. Erityisen tärkeitä olivat työväenliikkeen vaikutusvallan kasvu ja teollisuusjohtajien pyrkimys pysäyttää se. Maahanmuuttajien "bolshevismi" olikin käyttökelpoinen argumentti paitsi maahanmuuttajia myös amerikkalaisia työläisiä vastaan: teollisuusjohtajat painottivat että lakot ja työväenliike olivat tulosta siirtolaisten mukanaan tuomista "epäamerikkalaisista" ajatusmalleista, eivät yhteiskunnan epäoikeudenmukaisuudesta. Kongressin keskustelun lisäksi työssä käsitellään myös eri yhteiskunnallisten ryhmien ja vaikuttajien kantaa siirtolaisuuteen. Keskusteluun maahanmuutosta vaikuttivat etenkin eugenistit ja muut sosiaalitieteilijät, jotka väittivät itä- ja eteläeurooppalaisten olevan rodullisesti anglosakseja huonompia. Tämän väitteen vaikutusvaltaa lisäsivät yhteiskunnassa vallalla olleet ennakkoluulot, ja monet yhdistykset ja liikkeet (mm. Ku Klux Klan ja erilaiset isänmaalliset järjestöt) olivatkin tärkeitä rajoittamisen kannattajia. Keskustelu maahanmuutosta painottui ideologisiin ja tunteellisiin kysymyksiin, mutta rajoitusten taustalla oli myös konkreettisempia tekijöitä. Yhteiskunnan teollistuminen ja kaupungistuminen olivat pienentäneet siirtolaisista koituvaa taloudellista hyötyä: siirtolaisia ei enää tarvittu raivaamaan uusia viljelysmaita, kun taas tuotannon koneistuminen vähensi työvoiman tarvetta huomattavasti. Pitkän aikavälin taloudellisten tekijöiden roolin merkitys käy ilmeiseksi kun otetaan huomioon, että muut maahanmuuttomaat (esim. Kanada ja Australia) eivät juuri rajoittaneet siirtolaisuutta tänä aikana vaikka niissäkin esiintyi runsaasti rodullista ja kulttuurista maahanmuuttajavastaisuutta. Pääsyy rajoitusten vähäisyyteen näissä maissa oli juuri maahanmuuttajien tuoma taloudellinen hyöty, sekä teollisena työvoimana että maanviljelijöinä. Vaikka kiintiölakiehdotusten ympärillä käytiin kiivasta väittelyä, kongressi kuitenkin hyväksyi lait varsin suurella enemmistöllä. Siirtolaisia itseään lukuunottamatta varsin harvat näkivät lait haitallisina, kun taas useat erilaiset ryhmät katsoivat hyötyvänsä maahanmuuton rajoittamisesta. Avainsanat: siirtolaisuus, maahanmuutto, Yhdysvallat, 1920-luku, kiintiölait, maahanmuuton rajoittaminen

Field evaluation of 64 rootstocks for growth and yield of 'Kensington Pride' mango

Despite an abundance of polyembryonic genotypes and the need for rootstocks that improve scion yield and productivity, simultaneous field testing of a wide range of mango (Mangifera indica L.) genotypes as rootstocks has not previously been reported. In this experiment, we examined the growth and yield of 'Kensington Pride' on 64 mango genotypes of diverse origin during the first four seasons of fruit production to identify those worth longer-term assessment. We also recorded morphological characteristics of seedlings of 46 of these genotypes in an attempt to relate these measures to subsequent field performance. Tree canopy development on the most vigorous rootstocks was almost double that on the least vigorous. Growth rates differed by more than 160%. Cumulative marketable yield ranged from 36 kg/tree for the lowest yielding rootstock to 181 kg/tree for the most productive. Yield efficiency also differed markedly among the 64 rootstocks with the best treatment being 3.5 times more efficient than the poorest treatment. No relationship was found between yield efficiency and tree size, suggesting it is possible to select highly efficient rootstocks of differing vigor. Two genotypes ('Brodie' and 'MYP') stood out as providing high yield efficiency with small tree size. A further two genotypes ('B' and 'Watertank') were identified as offering high yield efficiency and large tree size and should provide high early yields at traditional tree spacing. Efforts to relate the morphology of different genotype seedlings to subsequent performance as a rootstock showed that nursery performance of mango seedlings is no indication of their likely behavior as a rootstock. The economic cost of poor yields and low yield efficiencies during the early years of commercial orchard production provide a rationale for culling many of the rootstock treatments in this experiment and concentrating future assessment on the top ~20% of the 64 treatments. Of these, 'MYP', 'B', 'Watertank', 'Manzano', and 'Pancho' currently show the most promise.

Sustainable and profitable grazing management in a highly variable environment-evidence and insights from a long term grazing trial in northern Australia.

Rainfall variability is a major challenge to sustainable management in semi-arid rangelands. We present empirical evidence from a large, long-term grazing trial in northern Australia on the relative performance of constant heavy stocking, moderate stocking at long-term carrying capacity and variable stocking in coping with climate variability over a range of rainfall years. Moderate stocking gave good economic returns, maintained pasture condition and minimised soil loss and runoff. Heavy stocking was neither sustainable nor profitable in the long term. Variable stocking generally performed well but suffered economic loss and some decline in pasture condition in the transition from good to poor years. Importantly, our results show that sustainable and profitable management are compatible in semi-arid rangelands.