Identification and inhibitory properties of a novel Ca(2+)/calmodulin antagonist.

We developed a high-throughput yeast-based assay to screen for chemical inhibitors of Ca(2+)/calmodulin-dependent kinase pathways. After screening two small libraries, we identified the novel antagonist 125-C9, a substituted ethyleneamine. In vitro kinase assays confirmed that 125-C9 inhibited several calmodulin-dependent kinases (CaMKs) competitively with Ca(2+)/calmodulin (Ca(2+)/CaM). This suggested that 125-C9 acted as an antagonist for Ca(2+)/CaM rather than for CaMKs. We confirmed this hypothesis by showing that 125-C9 binds directly to Ca(2+)/CaM using isothermal titration calorimetry. We further characterized binding of 125-C9 to Ca(2+)/CaM and compared its properties with those of two well-studied CaM antagonists: trifluoperazine (TFP) and W-13. Isothermal titration calorimetry revealed that binding of 125-C9 to CaM is absolutely Ca(2+)-dependent, likely occurs with a stoichiometry of five 125-C9 molecules to one CaM molecule, and involves an exchange of two protons at pH 7.0. Binding of 125-C9 is driven overall by entropy and appears to be competitive with TFP and W-13, which is consistent with occupation of similar binding sites. To test the effects of 125-C9 in living cells, we evaluated mitogen-stimulated re-entry of quiescent cells into proliferation and found similar, although slightly better, levels of inhibition by 125-C9 than by TFP and W-13. Our results not only define a novel Ca(2+)/CaM inhibitor but also reveal that chemically unique CaM antagonists can bind CaM by distinct mechanisms but similarly inhibit cellular actions of CaM.

Convict Criminology: Provocazioni da Oltreoceano. La Ricerca Etnografica in Carcere

This review essay describes the New School of Convict Criminology through an analysis of its main manifesto and some of the more recent articles which have been published on the subject. It suggests that this new brand of criminology is placed on a continuum with the established tradition of critical criminology without arriving at its most radical consequences: abolitionism. The school’s endeavor is that of launching a “realist criminology” able to change prisoners’ conditions and facilitating their re-entry in society, starting from consideration of their personal needs rather than from legislative issues. The School which was led by John Irwin is constituted by former prisoners and embrace ethnographic research as the only way to understand inmates’ conditions.

Acetylation of Rb by PCAF is required for nuclear localization and keratinocyte differentiation

Although the retinoblastoma protein (Rb) functions as a checkpoint in the cell cycle, it also regulates differentiation. It has recently been shown that Rb is acetylated during differentiation; however, the role of this modification has not been identified. Depletion of Rb levels with short hairpin RNA resulted in inhibition of human keratinocyte differentiation, delayed cell cycle exit and allowed cell cycle re-entry. Restoration of Rb levels rescued defects in differentiation and cell cycle exit and re-entry; however, re-expression of Rb with the major acetylation sites mutated did not. During keratinocyte differentiation, acetylation of Rb is mediated by PCAF and it is further shown that PCAF acetyltransferase activity is also required for normal differentiation. The major acetylation sites in Rb are located within the nuclear localization sequence and, although mutation did not alter Rb localization in cycling cells, the mutant is mislocalized to the cytoplasm during differentiation. Studies indicate that acetylation is a mechanism for controlling Rb localization in human keratinocytes, with either reduction of the PCAF or exogenous expression of the deacetylase SIRT1, resulting in mislocalization of Rb. These findings identify PCAF-mediated acetylation of Rb as an event required to retain Rb within the nucleus during keratinocyte differentiation.

MarcoPolo-R near earth asteroid sample return mission

MarcoPolo-R is a sample return mission to a primitive Near-Earth Asteroid (NEA) proposed in collaboration with NASA. It will rendezvous with a primitive NEA, scientifically characterize it at multiple scales,and return a unique sample to Earth unaltered by the atmospheric entry process or terrestrial weathering. MarcoPolo-R will return bulk samples (up to 2 kg) from an organic-rich binary asteroid to Earth for laboratory analyses, allowing us to: explore the origin of planetary materials and initial stages of habitable planet formation; identify and characterize the organics and volatiles in a primitive asteroid; understand the unique geomorphology, dynamics and evolution of a binaryNEA. This project is based on the previous Marco Polo mission study,which was selected for the Assessment Phase of the first round of Cosmic Vision. Its scientific rationale was highly ranked by ESA committees andit was not selected only because the estimated cost was higher than theallotted amount for an M class mission. The cost of Marco Polo-R will be reduced to within the ESA medium mission budget by collaboration withAPL (John Hopkins University) and JPL in the NASA program for coordination with ESA's Cosmic Vision Call. The baseline target is a binary asteroid (175706) 1996 FG3, which offers a very efficient operational and technical mission profile. A binary target also providesenhanced science return. The choice of this target will allow newinvestigations to be performed more easily than at a single object, andalso enables investigations of the fascinating geology and geophysics ofasteroids that are impossible at a single object. Several launch windows have been identified in the time-span 2020-2024. A number of otherpossible primitive single targets of high scientific interest have beenidentified covering a wide range of possible launch dates. The baselinemission scenario of Marco Polo-R to 1996 FG3 is as follows: a singleprimary spacecraft provided by ESA, carrying the Earth Re-entry Capsule, sample acquisition and transfer system provided by NASA, will be launched by a Soyuz-Fregat rocket from Kourou into GTO and using two space segment stages. Two similar missions with two launch windows, in 2021 and 2022 and for both sample return in 2029 (with mission durationof 7 and 8 years), have been defined. Earlier or later launches, in 2020 or 2024, also offer good opportunities. All manoeuvres are carried out by a chemical propulsion system. MarcoPolo-R takes advantage of three industrial studies completed as part of the previous Marco Polo mission (see ESA/SRE (2009)3, Marco Polo Yellow Book) and of the expertise of the consortium led by Dr. A.F. Cheng (PI of the NASA NEAR Shoemaker mission) of the JHU-APL, including JPL, NASA ARC, NASA LaRC, and MIT.

«Le grand retour» : le processus de rapatriement chez l’étudiant en échange à l’international

L’augmentation rapide de l’interdépendance mondiale, provoquée par le développement de la mondialisation, exige une redéfinition de la notion traditionnelle de l’éducation supérieure. Au Canada, comme dans le reste du monde, plusieurs universitaires, fonctionnaires du gouvernement et étudiants insistent maintenant sur l’intégration de l’internationalisation dans l’éducation supérieure à travers des échanges interculturels et des études à l’étranger, dans l’espoir que les générations canadiennes à venir développent une perspective globale et deviennent des « citoyens du monde » (Comité consultatif sur la stratégie du Canada en matière d’éducation internationale, 2012). Pourtant, pour garantir que l’étudiant qui participe à un échange profite le plus de son expérience internationale, nous devrons comprendre comment une telle expérience l’influence tant à court terme qu’à long terme. Bien que d’autres études se soient concentrées sur le court terme (le séjour à l’étranger et ses impacts immédiats), peu ont examiné le retour de l’étudiant, sa réintégration dans sa société d’origine et les effets subséquents à long terme, tels que les développements personnels qui pourraient suivre le rapatriement. Cette étude qualitative examine les témoignages de huit étudiants au premier cycle de l’Université de Montréal sur la façon dont ils ont vécu leur rapatriement à Montréal après un échange pédagogique à l’étranger. Quoique certains chercheurs présentent la notion de rapatriement comme une série d’événements déconnectés, notre analyse fait ressortir une tendance similaire dans tous nos témoignages qui nous permet dorénavant de considérer ce rapatriement comme un processus en trois étapes interconnectées. En empruntant à la théorie Intercultural Personhood de Kim (2008), nous sommes désormais en mesure de qualifier ces trois étapes comme étant le stress, l’adaptation et l’évolution. Non seulement cette interprétation nous aide à mieux comprendre les difficultés rencontrées par l’étudiant à l’occasion de son retour, mais elle facilite également l’identification des transformations identitaires qui apparaissent à ce moment-là et la manière dont ces transformations influencent le processus de rapatriement.

Spectrum simulation of rough and nanostructured targets from their 2D and 3D image by Monte Carlo methods

Corteo is a program that implements Monte Carlo (MC) method to simulate ion beam analysis (IBA) spectra of several techniques by following the ions trajectory until a sufficiently large fraction of them reach the detector to generate a spectrum. Hence, it fully accounts for effects such as multiple scattering (MS). Here, a version of Corteo is presented where the target can be a 2D or 3D image. This image can be derived from micrographs where the different compounds are identified, therefore bringing extra information into the solution of an IBA spectrum, and potentially significantly constraining the solution. The image intrinsically includes many details such as the actual surface or interfacial roughness, or actual nanostructures shape and distribution. This can for example lead to the unambiguous identification of structures stoichiometry in a layer, or at least to better constraints on their composition. Because MC computes in details the trajectory of the ions, it simulates accurately many of its aspects such as ions coming back into the target after leaving it (re-entry), as well as going through a variety of nanostructures shapes and orientations. We show how, for example, as the ions angle of incidence becomes shallower than the inclination distribution of a rough surface, this process tends to make the effective roughness smaller in a comparable 1D simulation (i.e. narrower thickness distribution in a comparable slab simulation). Also, in ordered nanostructures, target re-entry can lead to replications of a peak in a spectrum. In addition, bitmap description of the target can be used to simulate depth profiles such as those resulting from ion implantation, diffusion, and intermixing. Other improvements to Corteo include the possibility to interpolate the cross-section in angle-energy tables, and the generation of energy-depth maps.

Niveles de exposición a fungicidas ditiocarbamatos y su relación con las condiciones de trabajo en el sector floricultor en la Sabana de Bogotá D.C. (Cundinamarca) y Rionegro (Antioquia), Colombia, durante el año 2011

El interés del estudio de investigación se basó en recolectar datos de exposición ocupacional a plaguicidas ditiocarbamatos en el sector floricultor. Objetivo: Determinar los niveles de exposición a fungicidas ditiocarbamatos y su relación con las condiciones laborales de los trabajadores del sector floricultor en la Sabana de Bogotá D.C. (Cundinamarca) y Rionegro (Antioquia), Colombia, durante el año 2011. Materiales y Métodos: Se realizó un estudio de corte transversal, en 358 trabajadores de un total de 3700 empleados de 27 empresas del sector floricultor, 12 ubicadas en la Sabana de Bogotá (Cundinamarca) y 3 en Rionegro (Antioquia). Se recoleto información sobre condiciones de trabajo y antecedentes de exposición de la población y se determinaron los niveles de exposición a fungicidas ditiocarbamatos en muestra en orina mediante método Montesano. Conclusiones: Este estudio describe la forma como se utilizan y los niveles de exposición a fungicidas ditiocarbamatos ETU, en el sector floricultor en Colombia. Se dan recomendaciones para mejorar los tiempos de re-ingreso al cultivo según la categoría toxicológica de los productos.

Informality in the City: a Theoretical Analysis

This thesis theoretically studies the relationship between the informal sector (both in the labor and the housing market) and the city structure.

Transport and distribution of lindane and simazine in a riverine environment: measurements in bed sediments and modelling

Aquatic sediments often remove hydrophobic contaminants from fresh waters. The subsequent distribution and concentration of contaminants in bed sediments determines their effect on benthic organisms and the risk of re-entry into the water and/or leaching to groundwater. This study examines the transport of simazine and lindane in aquatic bed sediments with the aim of understanding the processes that determine their depth distribution. Experiments in flume channels (water flow of 10 cm s(-1)) determined the persistence of the compounds in the absence of sediment with (a) de-ionised water and (b) a solution that had been in contact with river sediment. In further experiments with river bed sediments in light and dark conditions, measurements were made of the concentration of the compounds in the overlying water and the development of bacterial/algal biofilms and bioturbation activity. At the end of the experiments, concentrations in sediments and associated pore waters were determined in sections of the sediment at 1 mm resolution down to 5 mm and then at 10 mm resolution to 50 mm depth and these distributions analysed using a sorption-diffusion-degradation model. The fine resolution in the depth profile permitted the detection of a maximum in the concentration of the compounds in the pore water near the surface, whereas concentrations in the sediment increased to a maximum at the surface itself. Experimental distribution coefficients determined from the pore water and sediment concentrations indicated a gradient with depth that was partly explained by an increase in organic matter content and specific surface area of the solids near the interface. The modelling showed that degradation of lindane within the sediment was necessary to explain the concentration profiles, with the optimum agreement between the measured and theoretical profiles obtained with differential degradation in the oxic and anoxic zones. The compounds penetrated to a depth of 40-50 rum over a period of 42 days. (C) 2004 Society of Chemical Industry.

”Tacksamhet för att jag fick ett nytt liv” : En kvalitativ studie om återanpassningsstrategier efter avtjänat fängelsestraff

Intresset för kriminalitet och individerna bakom de kriminella handlingarna ökar i samhället och återges i media dagligen. Det är just individen bakom brottet, hen som fängslas och får avtjäna sitt straff som denna studie riktar sitt fokus på. När fängelsegrindarna öppnas och återinträdet till samhället blir ett faktum; Hur tar då dessa individer sig tillbaka till samhället för att åter bli en del av det? Syftet med denna studie är att undersöka vilka återanpassningsstrategier som frigivna använder sig av samt hur samhällets bemötande påverkar strategierna. Studien baseras på självbiografier skrivna av fyra författare som alla levt ett kriminellt liv och som sedermera avtjänat ett eller flera fängelsestraff. Resultatet visar att det finns flera anpassningsstrategier som tas i bruk. Däribland att söka hjälp och stöd hos familj, vänner eller andra sociala grupper. Vidare återfinns det i strävan efter en ”ny identitet” vilket ofta sker med hjälp av tro. Att sysselsätta sig, ge något tillbaka till samhället, visa sin kreativitet i syfte att återfå sin kredibilitet kan ses som strategier som leder fram till det slutliga målet, kredibiliteten. Slutligen kunde ett samband mellan samhällets bemötande och återanpassningsstrategierna utrönas. Ju mer negativt bemötandet är desto fler återanpassningsstrategier behövs och arbetet för att uppnå dem blir mer krävande. Givet blir då att ett bemötande som fyllts av uppmuntran till individens förändring medför att färre strategier behövs och risken för återfall blir mindre.

Tertiary Journalism Education: Its Value in Cadet Selection at Metropolitan Media

Tertiary study in journalism has been a feature of the education of Australian journalists for decades. Yet the value of what is loosely termed a “journalism degree” continues to be debated, and many industry representatives remain sceptical of its value. Journalism educators have a number of ways of assessing the level of industry acceptance of journalism education. These include looking at the percentage of students who find employment and the percentage of journalism graduates who fill entry level positions. This paper addresses the latter category, looking at data on the employment of entry-level journalists at four major institutions over a period of several years.

Early induction of chalpains in rotenone-mediated neuronal apoptosis

Rotenone is an inhibitor of mitochondrial complex I that produces a model of Parkinson's disease (PD), where neurons undergo apoptosis by caspase-dependent and/or caspase-independent pathways. Inhibition of calpains has recently been shown to attenuate neuronal apoptosis. This study aims to establish for the first time, the time-point of calpain activation with respect to the caspase activation and the possibility of cell cycle re-entry in rotenone-mediated cell death. Immunoblot results revealed calpain activation occurred at 5, 10 h prior to caspase-3 activation (at 15 h), suggesting calpain activation was an earlier cellular event compared to caspase activation in the rotenone-mediated apoptosis. In addition, an upregulation of phospho-p53 was observed at 21 h. However, no expression or upregulation of cell cycle regulatory proteins including cdc25a, cyclin-D1 and cyclin-D3 were observed, strongly suggesting that cell cycle re-entry did not occur. These findings provide new insights into the differential patterns of calpain and caspase activation that result from rotenone poisoning and which may be relevant to the therapeutic management of PD.

UnitingCare West Outreach Services and the Good Lives Model of offender rehabiliation

UnitingCare West is a not-for-profit community services organisation committed to achieving justice, hope and opportunity for all, and works to support and empower in particular those most in need in the WA community. Through its program Outreach Services, it delivers a specialist re-entry service for sex offenders and men serving life and indeterminate sentences. The program has recently been reviewed by Dr Andrew Day from the Centre for Offender Reintegration, Deakin University with input from Dr Tony Ward, University of Victoria, Wellington, New Zealand. In this paper we describe the aims of the review, the process and findings and our ongoing work in developing a rationale for the service that is underpinned by the Good Lives Model (GLM) of offender rehabilitation. More generally, the presentation will seek to understand the needs of offenders who re-enter the community following long-term imprisonment in relation to those areas of need identified in the GLM.

Sources of stress in South African soccer coaches

It has been noted that coaches face a number of challenges, frustrations, conflicts and tensions, most of which translate into perceived stress. With the re-entry of South Africa into the international sporting arena, little is known about South African coaches and what specific stresses they experience. Thus, the present study used a mixed-method approach in exploring the perceptions of stress among South African soccer coaches. More specifically, 12 South African coaches were interviewed (using semi-structured interview guides) on their perceptions of sources of stress. Furthermore, 112 soccer coaches (at the provincial level and higher) were approached to complete a 32-item questionnaire on the sources of stress related to their job as coaches. Content analysis was used to evaluate the qualitative data while the descriptive data analysis was completed using the Statistical Package for Social Sciences (SPSS – version 16). The reliability was tested for the sources of stress (a= .817) for the 32 items. The sources of stress experienced by the coaches were evaluated. The results revealed the three main themes related to sources of stress were Resource Issues, External Pressure and Internal Capacity. Complementing these results, the top three sources of stress found through the descriptive statistics were lack of resources, fixture backlog and games where the outcome is critical, while the lowest three sources of stress were political interference, physical assaults from players and substituting a player. Specific academic and practical implications of the study the results were discussed.

The impact of religious diversity and revitalization on inter-religious education for citizenship and human rights

The unanticipated rise of religious diversity and the re-entry of religion to the public sphere have radically increased the need and demand for education about religions – how they contribute to social and cultural capital – and about the management of religious diversity. The global movement of people and cultures has brought religious diversity to nearly every major city. With diversity has come a renewed interest in the religious identity of others and how to incorporate religious diversity in ways that produce social cohesion. Religious diversity has also raised interest in a values discourse where once atheistic secularity prevailed, made faith-based social and health service delivery both more appealing to governments and more difficult to deliver, and has challenged societies to accommodate a wider range of religious needs and lifestyles. Policies designed to promote social justice and peace have little chance of success without taking seriously the religious dimensions to the issues involved. This context makes clear the need for opportunities to learn about the religions in a society at all levels of education – opportunities that include direct experience of the ‘other’, curricula that appreciate the worlds of faith, spirituality and religion rather than demeaning them, education that provides both historical depth and local reality. Some of this education will be in school, some in remedial work required for a generation or two of leaders who have been raised in ignorance of religion, or trained to despise it.