Evaluation of the year 1 literacy and numeracy checkpoints assessments trial - 2010

The draft Year 1 Literacy and Numeracy Checkpoints Assessments were in open and supported trial during Semester 2, 2010. The purpose of these trials was to evaluate the Year 1 Literacy and Numeracy Checkpoints Assessments (hereafter the Year 1 Checkpoints) that were designed in 2009 as a way to incorporate the use of the Year 1 Literacy and Numeracy Indicators as formative assessment in Year 1 in Queensland Schools. In these trials there were no mandated reporting requirements. The processes of assessment were related to future teaching decisions. As such the trials were trials of materials and the processes of using those materials to assess students, plan and teach in year 1 classrooms. In their current form the Year 1 Checkpoints provide assessment resources for teachers to use in February, June and October. They aim to support teachers in monitoring children's progress and making judgments about their achievement of the targeted P‐3 Literacy and Numeracy Indicators by the end of Year 1 (Queensland Studies Authority, 2010 p. 1). The Year 1 Checkpoints include support materials for teachers and administrators, an introductory statement on assessment, work samples, and a Data Analysis Assessment Record (DAAR) to record student performance. The Supported Trial participants were also supported with face‐to‐face and on‐line training sessions, involvement in a moderation process after the October Assessments, opportunities to participate in discussion forums as well as additional readings and materials. The assessment resources aim to use effective early years assessment practices in that the evidence is gathered from hands‐on teaching and learning experiences, rather than more formal assessment methods. They are based in a model of assessment for learning, and aim to support teachers in the “on‐going process of determining future learning directions” (Queensland Studies Authority, 2010 p. 1) for all students. Their aim is to focus teachers on interpreting and analysing evidence to make informed judgments about the achievement of all students, as a way to support subsequent planning for learning and teaching. The Evaluation of the Year 1 Literacy and Numeracy Checkpoints Assessments Supported Trial (hereafter the Evaluation) aimed to gather information about the appropriateness, effectiveness and utility of the Year 1 Checkpoints Assessments from early years’ teachers and leaders in up to one hundred Education Queensland schools who had volunteered to be part of the Supported Trial. These sample schools represent schools across a variety of Education Queensland regions and include schools with:  - A high Indigenous student population; - Urban, rural and remote school locations; - Single and multi‐age early phase classes; - A high proportion of students from low SES backgrounds. The purpose of the Evaluation was to: Evaluate the materials and report on the views of school‐based staff involved in the trial on the process, materials, and assessment practices utilised. The Evaluation has reviewed the materials, and used surveys, interviews, and observations of processes and procedures to collect relevant data to help present an informed opinion on the Year 1 Checkpoints as assessment for the early years of schooling. Student work samples and teacher planning and assessment documents were also collected. The evaluation has not evaluated the Year 1 Checkpoints in any other capacity than as a resource for Year 1 teachers and relevant support staff.

Host-pathogen checkpoints and population bottlenecks in persistent and intracellular uropathogenic Escherichia coli bladder infection

Bladder infections affect millions of people yearly, and recurrent symptomatic infections (cystitis) are very common. The rapid increase in infections caused by multidrug-resistant uropathogens threatens to make recurrent cystitis an increasingly troubling public health concern. Uropathogenic Escherichia coli (UPEC) cause the vast majority of bladder infections. Upon entry into the lower urinary tract, UPEC face obstacles to colonization that constitute population bottlenecks, reducing diversity, and selecting for fit clones. A critical mucosal barrier to bladder infection is the epithelium (urothelium). UPEC bypass this barrier when they invade urothelial cells and form intracellular bacterial communities (IBCs), a process which requires type 1 pili. IBCs are transient in nature, occurring primarily during acute infection. Chronic bladder infection is common and can be either latent, in the form of the quiescent intracellular reservoir (QIR), or active, in the form of asymptomatic bacteriuria (ASB/ABU) or chronic cystitis. In mice, the fate of bladder infection, QIR, ASB, or chronic cystitis, is determined within the first 24 h of infection and constitutes a putative host–pathogen mucosal checkpoint that contributes to susceptibility to recurrent cystitis. Knowledge of these checkpoints and bottlenecks is critical for our understanding of bladder infection and efforts to devise novel therapeutic strategies.

Identification of late larval stage developmental checkpoints in Caenorhabditis elegans regulated by insulin/IGF and steroid hormone signaling pathways.

Organisms in the wild develop with varying food availability. During periods of nutritional scarcity, development may slow or arrest until conditions improve. The ability to modulate developmental programs in response to poor nutritional conditions requires a means of sensing the changing nutritional environment and limiting tissue growth. The mechanisms by which organisms accomplish this adaptation are not well understood. We sought to study this question by examining the effects of nutrient deprivation on Caenorhabditis elegans development during the late larval stages, L3 and L4, a period of extensive tissue growth and morphogenesis. By removing animals from food at different times, we show here that specific checkpoints exist in the early L3 and early L4 stages that systemically arrest the development of diverse tissues and cellular processes. These checkpoints occur once in each larval stage after molting and prior to initiation of the subsequent molting cycle. DAF-2, the insulin/insulin-like growth factor receptor, regulates passage through the L3 and L4 checkpoints in response to nutrition. The FOXO transcription factor DAF-16, a major target of insulin-like signaling, functions cell-nonautonomously in the hypodermis (skin) to arrest developmental upon nutrient removal. The effects of DAF-16 on progression through the L3 and L4 stages are mediated by DAF-9, a cytochrome P450 ortholog involved in the production of C. elegans steroid hormones. Our results identify a novel mode of C. elegans growth in which development progresses from one checkpoint to the next. At each checkpoint, nutritional conditions determine whether animals remain arrested or continue development to the next checkpoint.

The making of a void sovereignty: political implications of the military checkpoints in the West Bank

Research on the Israeli checkpoints in the West Bank has emphasized not only that these checkpoints have dire implications for the Palestinians living there, at the personal, familial, and communal levels, and devastating eff ects on the Palestinian economy, but also that they have far-reaching consequences for the ability of the Palestinians to establish an independent political entity. At the same time, analysis of the Israeli forms of domination over the Palestinians has also stressed the role of a Palestinian governing authority in sustaining the Israeli rule, since the former relieves the latter of its responsibility to care for the occupied Palestinian population. This paper aims to address this apparent contradiction claiming that a comprehensive analysis of Israeli forms of domination requires a spatial examination of the operation of sovereignty with an assessment of governmentalizing arrays. This combined analysis suggests that a Palestinian sovereignty, but one which is emptied of its actual ruling power, is construed at the checkpoints as an epiphenomenon of Israeli apparatuses of control. © 2013 Pion and its Licensors.

Between Imaginary Lines: Violence and its Justifications at the Military Checkpoints in Occupied Palestine

Looking at one site, the Israeli checkpoints in the occupied Palestinian territory, this article seeks to understand the mechanisms by which violence can present itself as justifiable (or justified), even when it materializes within frames presumably set to annul it. We look at the checkpoints as a condensed microcosmos operating within two such frames. One is the prolonged IsraeliPalestinian ‘peace process’ (the checkpoints became a primary technology of control in the period following the beginning of the peace process), and the other is regulatory power (disciplinary and biopower), which in the Foucauldian framework presumably sidelines the violent form which sovereign power takes. We argue that the checkpoints, which dissect the Palestinian occupied territories into dozens of enclaves and which are one of the most effective and destructive means of control within the current stage of occupation, can be seen as more than obstacles in the way of Palestinian movement; we suggest that they also function as corrective technologies that are meant to fail. It is with this failure that violence can appear as justified. In order to show the operation of this embedded failure, we examine one mechanism operating within the checkpoints: ‘the imaginary line’. The imaginary line is both a component within, and an emblem of a mode of control that constantly undoes itself in order to summon violence. Since it is never visibly marked in the physical space, the imaginary line is bound to be unintentionally crossed, thereby randomly rendering Palestinians as ‘transgressors’ of the rule and thus facilitating eruptions of violence by the soldiers stationed at the checkpoints. This article proposes an analysis of this hidden demarcation of space in order to question the different relations between subjects and power which it both assumes and constitutes.

Bcl-xL regulation and function in cell cycle checkpoints and progression

Quelques évidences suggèrent que Bcl-xL, un membre anti-apoptotique de la famille Bcl-2, possède également des fonctions au niveau du cycle cellulaire et de ses points-contrôle. Pour étudier la régulation et fonction de Bcl-xL au cours du cycle cellulaire, nous avons généré et exprimé dans des cellules humaines une série de mutants de phosphorylation incluant Thr41Ala, Ser43Ala, Thr47Ala, Ser49Ala, Ser56Ala, Ser62Ala et Thr115Ala. L'analyse de cette série de mutants révèle que les cellules exprimant Bcl-xL(Ser62Ala) sont moins stables au point-contrôle G2 du cycle cellulaire comparées aux cellules exprimant le type sauvage ou les autres mutants de phosphorylation incluant Thr41Ala, Ser43Ala, Thr47Ala, Ser56Ala et Thr115Ala. Les études de cinétiques de phosphorylation et de localisation de phospho-Bcl-xL(Ser62) dans des cellules synchronisées et suite à l'activation du point-contrôle en G2 médié par l'étoposide (VP16), nous indiquent que phospho-Bcl-xL(Ser62) migre dans les corps nucléolaires durant l'arrêt en G2 dans les cellules exposées au VP16. Une série d'expériences incluant des essais kinase in vitro, l'utilisation d'inhibiteurs pharmacologiques et d'ARN interférant, nous révèlent que Polo kinase 1 (PLK1) et MAPK9/JNK2 sont les protéines kinase impliquées dans la phosphorylation de Bcl-xL(Ser62), et pour son accumulation dans les corps nucléolaires pendant le point-contrôle en G2. Nos résultats indiquent que durant le point-contrôle en G2, phospho-Bcl-xL(Ser62) se lie et se co-localise avec CDK1(CDC2), le complexe cycline-kinase qui contrôle l'entrée en mitose. Nos résultats suggèrent que dans les corps nucléolaires, phospho-Bcl-xL(Ser62) stabilise l'arrêt en G2 en séquestrant CDK1(CDC2) pour retarder l'entrée en mitose. Ces résultats soulignent également que les dommages à l'ADN influencent la composition des corps nucléolaires, structure nucléaire qui émerge maintenant comme une composante importante de la réponse aux dommages à l'ADN. Dans une deuxième étude, nous décrivons que les cellules exprimant le mutant de phosphorylation Bcl-xL(Ser62Ala) sont également plus stables au point-contrôle de l'assemblage du fuseau de la chromatine (SAC) suite à une exposition au taxol, comparées aux cellules exprimant le type sauvage ou d'autres mutants de phosphorylation de Bcl-xL, incluant Thr41Ala, Ser43Ala, Thr47Ala, Ser56Ala. Cet effet est indépendent de la fonction anti-apoptotique de Bcl-xL. Bcl-xL(Ser62) est fortement phosphorylé par PLK1 et MAPK14/SAPKp38α à la prométaphase, la métaphase et à la frontière de l'anaphase, et déphosphorylé à la télophase et la cytokinèse. Phospho-Bcl-xL(Ser62) se trouve dans les centrosomes avec γ-tubuline, le long du fuseau mitotique avec la protéine moteure dynéine et dans le cytosol mitotique avec des composantes du SAC. Dans des cellules exposées au taxol, phospho-Bcl-xL(Ser62) se lie au complexe inhibiteur CDC20/MAD2/BUBR1/BUB3, alors que le mutant Bcl-xL(Ser62Ala) ne se lie pas à ce complexe. Ces résultats indiquent que durant le SAC, la phosphorylation de Bcl-xL(Ser62) accélère la résolution du SAC et l'entrée des cellules en anaphase. Des expériences bloquant l'expression de Bcl-xL révèlent ègalement un taux très élevé de cellules tétraploïdes et binuclées après un traitement au nocodazole, consistant avec une fonction de Bcl-xL durant la mitose et dans la stabilité génomique. Dans la troisième étude, l'analyse fonctionnelle de cette série de mutants de phosphorylation indique également que les cellules exprimant Bcl-xL(Ser49Ala) sont moins stables durant le point-contrôle G2 et entre en cytokinèse plus lentement dans des cellules exposées aux inhibiteurs de la polymérisation/dépolymérisation des tubulines, composantes des microtubules. Ces effets de Bcl-xL(Ser49Ala) sont indépendents de sa fonction anti-apoptotique. La phosphorylation de Bcl-xL(Ser49) est dynamique au cours du cycle cellulaire. Dans des cellules synchronisées, Bcl-xL(Ser49) est phosphorylé en phase S et G2, déphosphorylé à la prométaphase, la métaphase et à la frontière de l'anaphase, et re-phosphorylé durant la télophase et la cytokinèse. Au cours du point-contrôle G2 induit par les dommages à l'ADN, un pool important de phospho-Bcl-xL(Ser49) se trouve aux centrosomes, un site important pour la régulation de l'entrée en mitose. Durant la télophase et la cytokinèse, phospho-Bcl-xL(Ser49) se trouve le long des microtubules avec la protéine moteure dynéine et dans le cytosol mitotique. Finalement, nos résultats suggèrent que PLK3 est responsable de la phosphorylation de Bcl-xL(Ser49), une protéine kinase impliquée pour l'entrée des cellules en mitose et pour la progression de la mitose jusqu'à la division cellulaire.

Implementação de recuperação por retorno de aplicações distribuídas baseada em checkpoints coordenados

A recuperação por retorno baseada em checkpointing é largamente usada como técnica de tolerância a falhas. O modelo complexo de sistemas distribuídos tem motivado o desenvolvimento de diversos algoritmos na tentativa de encontrar soluções mais simples e eficientes. Os processos que formam o sistema distribuído podem coordenar suas operações para garantir que o conjunto de checkpoints locais componha um estado global consistente (linha de recuperação). A partir desse estado, no caso de ocorrência de falhas, o sistema pode ser recuperado e a computação retomada a partir de um momento anterior ao da manifestação da falha, evitando o retrocesso para o estado inicial da computação e prevenindo a ocorrência de prejuízos com a perda de todo processamento até então realizado. No Grupo de Tolerância a Falhas da UFRGS foi proposto recentemente um algoritmo que é voltado para aplicações que executam em sistemas distribuídos assíncronos que se comunicam exclusivamente pela troca de mensagens. Ele opera com salvamento coordenado de checkpoints (não bloqueando as aplicações) e prevê o tratamento de mensagens órfãs e perdidas. Os mecanismos do algoritmo sugerem que nenhuma alteração deveria ser realizada no código das aplicações, criando a possibilidade de implementação transparente sob o ponto de vista dos usuários e dos programadores das aplicações. Como o algoritmo não requer o bloqueio das aplicações, a sobrecarga imposta pelos mecanismos à execução livre de falhas é pequena. Além disso, o processo de recuperação tende a ser efetuado rapidamente, uma vez que é garantida a existência de uma linha de recuperação consistente, facilmente identificada Este trabalho apresenta as decisões de projeto, a implementação, os resultados e a avaliação de desempenho desse algoritmo. A avaliação das alternativas de implementação resultou na decisão de uma implementação então realizada diretamente sobre o sistema operacional Linux, sem recorrer a protocolos auxiliares para garantir a execução dos serviços e sem a necessidade de adaptações no código das aplicações nem no código do sistema operacional. Adicionalmente, os resultados comprovaram a expectativa inicial de que o algoritmo causaria pouca sobrecarga no sistema (menos de 2%), embora ele ainda apresente alta dependência do tamanho dos checkpoints salvos.

The Drosophila chk2 gene loki is essential for embryonic DNA double-strand-break checkpoints induced in S phase or G2

Cell cycle checkpoints are signal transduction pathways that control the order and timing of cell cycle transitions, ensuring that critical events are completed before the occurrence of the next cell cycle transition. The Chk2 family of kinases is known to play a central role in mediating the cellular responses to DNA damage or DNA replication blocks in various organisms. Here we show through a phylogenetic study that the Drosophila melanogaster serine/threonine kinase Loki is the homolog of the yeast Mek1p, Rad53p, Dun1p, and Cds1 proteins as well as the human Chk2. Functional analyses allowed us to conclude that, in flies, chk2 is involved in monitoring double-strand breaks (DSBs) caused by irradiation during S and G2 phases. In this process it plays an essential role in inducing a cell cycle arrest in embryonic cells. Our results also show that, in contrast to C. elegans chk2, Drosophila chk2 is not essential for normal meiosis and recombination, and it also appears to be dispensable for the MMS-induced DNA damage checkpoint and the HU-induced DNA replication checkpoint during larval development. In addition, Drosophila chk2 does not act at the same cell cycle phases as its yeast homologs, but seems rather to be involved in a pathway similar to the mammalian one, which involves signaling through the ATM/Chk2 pathway in response to genotoxic insults. As mutations in human chk2 were linked to several cancers, these similarities point to the usefulness of the Drosophila model system.

Potent inhibition of tumor survival in vivo by β-lapachone plus taxol: Combining drugs imposes different artificial checkpoints

Ablation of tumor colonies was seen in a wide spectrum of human carcinoma cells in culture after treatment with the combination of β-lapachone and taxol, two low molecular mass compounds. They synergistically induced death of cultured ovarian, breast, prostate, melanoma, lung, colon, and pancreatic cancer cells. This synergism is schedule dependent; namely, taxol must be added either simultaneously or after β-lapachone. This combination therapy has unusually potent antitumor activity against human ovarian and prostate tumor prexenografted in mice. There is little host toxicity. Cells can commit to apoptosis at cell-cycle checkpoints, a mechanism that eliminates defective cells to ensure the integrity of the genome. We hypothesize that when cells are treated simultaneously with drugs activating more than one different cell-cycle checkpoint, the production of conflicting regulatory signaling molecules induces apoptosis in cancer cells. β-Lapachone causes cell-cycle delays in late G1 and S phase, and taxol arrests cells at G2/M. Cells treated with both drugs were delayed at multiple checkpoints before committing to apoptosis. Our findings suggest an avenue for developing anticancer therapy by exploiting apoptosis-prone “collisions” at cell-cycle checkpoints.

Replication Factor C3 of Schizosaccharomyces pombe, a Small Subunit of Replication Factor C Complex, Plays a Role in Both Replication and Damage Checkpoints

We report here the isolation and functional analysis of the rfc3+ gene of Schizosaccharomyces pombe, which encodes the third subunit of replication factor C (RFC3). Because the rfc3+ gene was essential for growth, we isolated temperature-sensitive mutants. One of the mutants, rfc3-1, showed aberrant mitosis with fragmented or unevenly separated chromosomes at the restrictive temperature. In this mutant protein, arginine 216 was replaced by tryptophan. Pulsed-field gel electrophoresis suggested that rfc3-1 cells had defects in DNA replication. rfc3-1 cells were sensitive to hydroxyurea, methanesulfonate (MMS), and gamma and UV irradiation even at the permissive temperature, and the viabilities after these treatments were decreased. Using cells synchronized in early G2 by centrifugal elutriation, we found that the replication checkpoint triggered by hydroxyurea and the DNA damage checkpoint caused by MMS and gamma irradiation were impaired in rfc3-1 cells. Association of Rfc3 and Rad17 in vivo and a significant reduction of the phosphorylated form of Chk1 in rfc3-1 cells after treatments with MMS and gamma or UV irradiation suggested that the checkpoint signal emitted by Rfc3 is linked to the downstream checkpoint machinery via Rad17 and Chk1. From these results, we conclude that rfc3+ is required not only for DNA replication but also for replication and damage checkpoint controls, probably functioning as a checkpoint sensor.

Mammalian mad2 and bub1/bubR1 recognize distinct spindle-attachment and kinetochore-tension checkpoints

Metaphase checkpoint controls sense abnormalities of chromosome alignment during mitosis and prevent progression to anaphase until proper alignment has been attained. A number of proteins, including mad2, bub1, and bubR1, have been implicated in the metaphase checkpoint control in mammalian cells. Metaphase checkpoints have been shown, in various systems, to read loss of either spindle tension or microtubule attachment at the kinetochore. Characteristically, HeLa cells arrest in metaphase in response to low levels of microtubule inhibitors that leave an intact spindle and a metaphase plate. Here we show that the arrest induced by nanomolar vinblastine correlates with loss of tension at the kinetochore, and that in response the checkpoint proteins bub1 and bubR1 are recruited to the kinetochore but mad2 is not. mad2 remains competent to respond and is recruited at higher drug doses that disrupt spindle association with the kinetochores. Further, although mad2 forms a complex with cdc20, it does not associate with bub1 or bubR1. We conclude that mammalian bub1/bubR1 and mad2 operate as elements of distinct pathways sensing tension and attachment, respectively.

Checkpoints in the progression of autoimmune disease: lessons from diabetes models.

In the last few years, data from experiments employing transgenic models of autoimmune disease have strengthened a particular concept of autoimmunity: disease results not so much from cracks in tolerance induction systems, leading to the generation of anti-self repertoire, as from the breakdown of secondary systems that keep these cells in check. T cells with anti-self specificities are readily found in disease-free individuals but ignore target tissues. This is also the case in some transgenic models, in spite of overwhelming numbers of autoreactive cells. In other instances, local infiltration and inflammation result, but they are well tolerated for long periods of time and do not terminally destroy target tissue. We review the possible molecular and cellular mechanisms that underlie these situations, with a particular emphasis on the destruction of pancreatic beta cells in transgenic models of insulin-dependent disease.

p53 controls both the G2/M and the G1 cell cycle checkpoints and mediates reversible growth arrest in human fibroblasts.

Increased expression of wild-type p53 in response to DNA damage arrests cells late in the G1 stage of the cell cycle by stimulating the synthesis of inhibitors of cyclin-dependent kinases, such as p21/WAF1. To study the effects of p53 without the complication of DNA damage, we used tetracycline to regulate its expression in MDAH041 human fibroblasts that lack endogenous p53. When p53 is expressed at a level comparable to that induced by DNA damage in other cells, most MDAH041 cells arrested in G1, but a significant fraction also arrested in G2/M. Cells released from a mimosine block early in S phase stopped predominantly in G2/M in the presence of p53, confirming that p53 can mediate arrest at this stage, as well as in G1. In these cells, there was appreciable induction of p21/WAF1. MDAH041 cells arrested by tetracycline-regulated p53 for as long as 20 days resumed growth when the p53 level was lowered, in striking contrast to the irreversible arrest mediated by DNA damage. Therefore, irreversible arrest must involve processes other than or in addition to the interaction of p53-induced p21/WAF1 with G1 and G2 cyclin-dependent kinases.