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The beamline optics and endstations at branch B of the Versatile Soft X-ray (VerSoX) beamline B07 at Diamond Light Source are described. B07-B provides medium-flux X-rays in the range 45-2200 eV from a bending magnet source, giving access to local electronic structure for atoms of all elements from Li to Y. It has an endstation for high-throughput X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine-structure (NEXAFS) measurements under ultrahigh-vacuum (UHV) conditions. B07-B has a second endstation dedicated to NEXAFS at pressures from UHV to ambient pressure (1 atm). The combination of these endstations permits studies of a wide range of interfaces and materials. The beamline and endstation designs are discussed in detail, as well as their performance and the commissioning process.

Background: Literature reveals that guided play promotes the development of visuospatial abilities essential for learning to read, write and do mathematics. However, most of these findings have focused on older children who are already literate, and the tests and the instruments used were designed for children in Western contexts. Aim: As there is little data on the development of visuospatial abilities in pre-literate children in African contexts, this study set out to explore the effects of using a guided block play intervention on the development of these abilities in pre-literate children. Setting: The study was carried out in two classrooms (one experimental and the other comparative) in each of two schools, one in South Africa and one in Kenya. Methods: The study used a pre- and post-test, quasi-experimental, mixed-methods approach. The intervention and test used, namely, the Visual Perception Aspects Test, were designed and validated in African contexts. Results: The data revealed that using the 6 Brick Duplo Block guided play approach statistically significantly accelerated the development of visuospatial abilities in pre-literate children in the experimental groups over those in the control groups (no intervention). The data also revealed that the greatest improvements were made among children who had few prior opportunities to engage in guided play using physical manipulatives. Conclusion: The overall findings of the study suggest that the development of aspects of visuospatial perception is accelerated when teachers use this approach to facilitate guided play. This finding has implications for promoting the development of reading, writing and numeracy skills in pre-literate children

This qualitative interpretive exploratory case study investigated a sample of South African teachers' perceptions of the requirements for successful implementation of Information and Communication Technology (ICT) Professional Teacher Development (PTD) within disadvantaged South African township schools in the Port Elizabeth district in South Africa. The participating teachers' (n=30) perceptions and experience of ICT PTD were explored via qualitative semi-structured interviews, an open-ended questionnaire, internet user group responses, reflective journal writing and facilitator reflections. The findings indicate that they value three aspects, namely facilitator related aspects, training context aspects and school related aspects. These findings underpin the C[superscript 2]RHOAR[superscript 3]FS[superscript 2]R[superscript 2] framework offered as a heuristic for ICT related PTD and subsequent school and classroom implementation. The C[superscript 2]RHOAR[superscript 3]FS[superscript 2]R[superscript 2] acronym refers to Care, Competence, Relate, Hands-on, On-going, Assessment, Reflection, Read, Revise-replan, Feedback, Share, Support, Recognition and Resources. The expectations of the teachers resonate with international expectations of Professional Teacher Development and underscore the magnitude of the task for those who aspire to meet the challenge they present. (Contains 1 figure.)

This case study, involving 30 participating teachers from six previously disadvantaged South African schools, provides data on teacher perceptions of the challenges related to implementing Information and Communication Technology (ICT). The schools had minimal resources as a residual result of the South African apartheid policy prior to 1994 and are located in areas that lack basic infrastructure. Twenty computers were provided to each of the schools by a donor solicited to support an ICT training intervention conducted by academics at the Nelson Mandela Metropolitan University (NMMU) in South Africa. A quantitative Likert scale questionnaire, qualitative interviews and a qualitative open-ended questionnaire were used to gather data. These data suggest that, despite the fact of the schools were provided with computers and teacher training, several first and second order barriers still exist. Examples of these barriers are insufficient ICT resources for the large classes that have to be taught, lack of project leadership within the schools, and a need for ongoing training and support. These barriers appear to have not allowed the teachers and schools to go beyond an initial integration phase. The data generated, the literature consulted, as well as the involvement of the authors in the ICT implementation and training process over a period of two years, underpin the suggestions made for consideration when attempting to implement ICT focused interventions, particularly in schools with limited infrastructure and support. An implementation heuristic is proposed for consideration by those involved with ICT implementation in comparable situations. (Contains 4 tables and 1 figure.)

The focus of this paper is on selected recent South African research studies that have explored efforts to promote the discussion, writing, and arguing aspects of scientific literacy in primary and middle schools, particularly amongst second-language learners. These studies reveal improvements in the participants' abilities to both use the "science notebooks" approach and argue their findings, as well as statistically significant improvement in their problem solving skills. The positive findings of these studies, and the call for attention to be paid to the fundamental sense of scientific literacy by a number of international researchers, resulted in the development of an integrated learning strategies approach. This approach not only specifically includes classroom discussion, argumentation and writing strategies to learn science, but also provides teachers with ideas and techniques to stimulate their learners to develop their own investigable questions, plan and execute a successful investigation in the classroom, and present their findings to an authentic audience. Findings on the effect of the strategy on learners' general literacy skills, both in their home language and the language of learning and teaching in their schools, are reported. (Contains 2 tables and 5 figures.)

The intention of this study is to explore mathematical discourse and teaching methods in Grades 6 and 7 of primary school in the Eastern Cape Province of South Africa. The school's student population changed from predominately white English/Afrikaans-speaking learners before the 1994 election to predominately black Xhosa-speaking students in 2004. The language of teaching and learning is strictly English, and most teachers cannot speak or understand Xhosa. Additionally, some Xhosa-speaking learners cannot clearly articulate their thinking and reasoning in English. The study demonstrates two mathematics classroom interactions and illustrates how language plays a pivotal role in classroom discourse. The findings of the study suggest that working with peers in Xhosa may facilitate learners' skills and development of conceptual understanding of mathematics. Furthermore, the study shows that requiring verbal discourse in the classroom to be only in English limited the learners' success in displaying their mathematical understanding, which in turn made them appear to be lower achieving than those who spoke only in English.

Colorectal cancers (CRCs) account for nearly 10% of all cancer deaths in industrialized countries. Recent evidence points to a central role for the nuclear receptor liver receptor homolog-1 (LRH-1) in intestinal tumorigenesis. Interaction of LRH-1 with the Wnt/β-catenin pathway, highly active in a critical subpopulation of CRC cells, underscores the importance of elucidating LRH-1's role in this disease. Reduction of LRH-1 diminishes tumor burden in murine models of CRC; however, it is not known whether LRH-1 is required for tumorigenesis, for proliferation, or for both. In this work, we address this question through shRNA-mediated silencing of LRH-1 in established CRC cell lines. LRH-1 mRNA knockdown results in significantly impaired proliferation in a cell line highly expressing the receptor and more modest impairment in a cell line with moderate LRH-1 expression. Cell-cycle analysis shows prolongation of G0/G1 with LRH-1 silencing, consistent with LRH-1 cell-cycle influences in other tissues. Cluster analysis of microarray gene expression demonstrates significant genome wide alterations with major effects in cell-cycle regulation, signal transduction, bile acid and cholesterol metabolism, and control of apoptosis. This study demonstrates a critical proproliferative role for LRH-1 in established colon cancer cell lines. LRH-1 exerts its effects via multiple signaling networks. Our results suggest that selected CRC patients could benefit from LRH-1 inhibitors.

Transcription factor II D (TFIID) is a multiprotein complex that nucleates formation of the basal transcription machinery. TATA binding protein-associated factors 1 and 7 (TAF1 and TAF7), two subunits of TFIID, are integral to the regulation of eukaryotic transcription initiation and play key roles in preinitiation complex (PIC) assembly. Current models suggest that TAF7 acts as a dissociable inhibitor of TAF1 histone acetyltransferase activity and that this event ensures appropriate assembly of the RNA polymerase II-mediated PIC before transcriptional initiation. Here, we report the 3D structure of a complex of yeast TAF1 with TAF7 at 2.9 Å resolution. The structure displays novel architecture and is characterized by a large predominantly hydrophobic heterodimer interface and extensive cofolding of TAF subunits. There are no obvious similarities between TAF1 and known histone acetyltransferases. Instead, the surface of the TAF1-TAF7 complex contains two prominent conserved surface pockets, one of which binds selectively to an inhibitory trimethylated histone H3 mark on Lys27 in a manner that is also regulated by phosphorylation at the neighboring H3 serine. Our findings could point toward novel roles for the TAF1-TAF7 complex in regulation of PIC assembly via reading epigenetic histone marks.

Cholangiocytes, bile duct lining cells, actively adjust the amount of cholesterol and bile acids in bile through expression of enzymes and channels involved in transportation and metabolism of the cholesterol and bile acids. Herein, we report molecular mechanisms regulating bile acid biosynthesis in cholangiocytes. Among the cytochrome p450 (Cyp) enzymes involved in bile acid biosynthesis, sterol 27-hydroxylase (Cyp27) that is the rate-limiting enzyme for the acidic pathway of bile acid biosynthesis expressed in cholangiocytes. Expression of other Cyp enzymes for the basic bile acid biosynthesis was hardly detected. The Cyp27 expression was negatively regulated by a hydrophobic bile acid through farnesoid X receptor (FXR), a nuclear receptor activated by bile acid ligands. Activated FXR exerted the negative effects by inducing an expression of fibroblast growth factor 15/19 (FGF15/19). Similar to its repressive function against cholesterol 7α-hydroxylase (Cyp7a1) expression in hepatocytes, secreted FGF15/19 triggered Cyp27 repression in cholangiocytes through interaction with its cognate receptor fibroblast growth factor receptor 4 (FGFR4). The involvements of FXR and FGFR4 for the bile acid-induced Cyp27 repression were confirmed in vivo using knockout mouse models. Different from the signaling in hepatocytes, wherein the FGF15/19-induced repression signaling is mediated by c-Jun N-terminal kinase (JNK), FGF15/19-induced Cyp27 repression in cholangiocytes was mediated by p38 kinase. Thus, the results collectively suggest that cholangiocytes may be able to actively regulate bile acid biosynthesis in cholangiocytes and even hepatocyte by secreting FGF15/19. We suggest the presence of cholangiocyte-mediated intrahepatic feedback loop in addition to the enterohepatic feedback loop against bile acid biosynthesis in the liver.

Research has shown improvements in science, mathematics, and language scores when classroom discussion is employed in school-level science and mathematics classes. Studies have also shown statistically and practically significant gains in children's reasoning abilities as measured by the Raven's Standard Progressive Matrices test when employing the practice of "exploratory talk." While these studies suggest that transfer of learning had taken place, a number of dialog-intensive designs have failed to find positive results, only reported delayed transfer, or have been criticized in terms of methodological rigor, small sample sizes, or because they have only shown small effect sizes. In this study, the claim is made that a particular set of studies which focused on exploratory talk and reasoning abilities, and which used designs that are better positioned to meet the standards mentioned above when presenting data in support of far transfer, provides robust evidence of far transfer within the framework of Barnett and Ceci's taxonomy of transfer. Possible relationships between exploratory talk, argumentation, and key domains in the science of learning are considered in an attempt to explain the apparent far transfer effects when children engage in exploratory talk.

Nuclear receptors (NRs) are an important group of ligand-dependent transcriptional factors. Presently, no natural or synthetic ligand has been identified for a large group of orphan NRs. Small molecules to target these orphan NRs will provide unique resources for uncovering regulatory systems that impact human health and to modulate these pathways with drugs. The orphan NR tailless (TLX, NR2E1), a transcriptional repressor, is a major player in neurogenesis and Neural Stem Cell (NSC) derived brain tumors. No chemical probes that modulate TLX activity are available, and it is not clear whether TLX is druggable. To assess TLX ligand binding capacity, we created homology models of the TLX ligand binding domain (LBD). Results suggest that TLX belongs to an emerging class of NRs that lack LBD helices α1 and α2 and that it has potential to form a large open ligand binding pocket (LBP). Using a medium throughput screening strategy, we investigated direct binding of 20,000 compounds to purified human TLX protein and verified interactions with a secondary (orthogonal) assay. We then assessed effects of verified binders on TLX activity using luciferase assays. As a result, we report identification of three compounds (ccrp1, ccrp2 and ccrp3) that bind to recombinant TLX protein with affinities in the high nanomolar to low micromolar range and enhance TLX transcriptional repressive activity. We conclude that TLX is druggable and propose that our lead compounds could serve as scaffolds to derive more potent ligands. While our ligands potentiate TLX repressive activity, the question of whether it is possible to develop ligands to de-repress TLX activity remains open.

A high-throughput screening campaign was conducted to identify small molecules with the ability to inhibit the interaction between the vitamin D receptor (VDR) and steroid receptor coactivator 2. These inhibitors represent novel molecular probes for modulating gene regulation mediated by VDR. Peroxisome proliferator-activated receptor (PPAR) δ agonist GW0742 was among the identified VDR-coactivator inhibitors and has been characterized herein as a pan nuclear receptor antagonist at concentrations of > 12.1 μM. The highest antagonist activity for GW0742 was found for VDR and the androgen receptor. Surprisingly, GW0742 behaved as a PPAR agonist and antagonist, activating transcription at lower concentrations and inhibiting this effect at higher concentrations. A unique spectroscopic property of GW0742 was identified as well. In the presence of rhodamine-derived molecules, GW0742 increased the fluorescence intensity and level of fluorescence polarization at an excitation wavelength of 595 nm and an emission wavelength of 615 nm in a dose-dependent manner. The GW0742-inhibited NR-coactivator binding resulted in a reduced level of expression of five different NR target genes in LNCaP cells in the presence of agonist. Especially VDR target genes CYP24A1, IGFBP-3, and TRPV6 were negatively regulated by GW0742. GW0742 is the first VDR ligand inhibitor lacking the secosteroid structure of VDR ligand antagonists. Nevertheless, the VDR-meditated downstream process of cell differentiation was antagonized by GW0742 in HL-60 cells that were pretreated with the endogenous VDR agonist 1,25-dihydroxyvitamin D3.

Recently, the South African Institute of Physics undertook a major review of university physics education. The report highlighted the necessity for further transformation of the teaching of physics, particularly in relation to the teaching of under-prepared students. In this article we examine how physics lecturers in South Africa reported how they respond to the teaching challenges that they face in terms of representational competence. We argue that the goal of any undergraduate degree is the production of disciplinary literate graduates, where disciplinary literacy refers to the ability to competently deal with the various representational formats used within the discipline. For physics the development of disciplinary literacy involves competence in a wide range of representations, such as written and oral languages, diagrams, graphs, mathematics, apparatus and simulations. Our interest in this study was the way in which individual physics lecturers described how they deal with their students' lack of representational competence. To this end, we interviewed 20 physics lecturers from five purposefully selected representative South African universities about their students' lack of representational competence and the educational strategies they use for dealing with this problem. These interviews were transcribed verbatim and analysed for potential patterns. Iterative, interpretive analysis resulted in the identification of six qualitatively different response strategies that South African physics lecturers indicate they invoke to deal with their students' lack of representational competence. We suggest that an understanding of this range of possible response strategies will allow physics lecturers to better understand their own responses and those of their peers, and that this, in turn, may lead to changes in educational practice. Based on the differences in individual response strategies that we find, we further argue that inter- and intra-faculty discussions about undergraduate disciplinary literacy goals have the distinct potential for reforming South African undergraduate physics. Here, we suggest that the disciplinary literacy discussion matrix that we used to initiate dialogue in our interviews may also double as a useful starting point for such faculty discussions.

This study investigated a sample of isiXhosa mother tongue-speaking science teachers', their pupils', and adult local community members' awareness of Xhosa indigenous knowledge. It also investigated what aspects of this knowledge they value and think should and could be integrated into the school science curriculum and their reasons for suggesting that it should (or should not) be incorporated. The participating teachers voluntarily completed an open-ended questionnaire. On completion, they were given the task of administering the questionnaire to at least 1 of their pupils and 1 community member who they believed could contribute ideas about indigenous knowledge that might relate to science education. Interviews were held with a small sample of teachers and community members. The data generated suggest that there is a shared awareness of indigenous knowledge across the respondents (teachers, pupils, and community members). The reasons given for including indigenous knowledge in the school curriculum related mainly to the realm of recognition (social justice and cultural sensitivity), and there was also little evidence that the respondents were aware of current understandings underpinning the demarcation of science and indigenous knowledge as disciplines.

Problems of poor performance in science and mathematics education have been related to language deficiencies, including writing skills. Writing to learn science is an important skill but is not easy to acquire, especially when children learn in a second language. In order to investigate possibilities for developing writing in South African and Swedish science classrooms a multiple case study design was employed using classroom observations, teacher interviews and samples of learners work produced in science second-language classrooms in both countries over a period of 6 months. The research questions were 'what text types do learners in a grade 6 Science classroom produce, and how are they assisted to produce such text types?' Four major themes emerged, namely, the use of pre-determined text types; evidence of a spoken text-type discourse; teachers' lack of knowledge about text types; and lack of support in assisting learners in producing written text. These themes have implications in terms of understanding the current situation and providing a point of departure for assisting teachers and children to develop the skill of writing to learn science, an implicit aim of the curricula in both countries.

This study focuses on the effects of the exposure of pre-service education students (n=87) to a variety of toys used as educative curriculum material in an attempt to develop their understanding of energy. Changes in their knowledge, their confidence in terms of this knowledge, and the reasons they attributed for any changes in both their knowledge and confidence were investigated. A single group pre-post design was utilised which included both the use of an online pre-post intervention questionnaire and a 'pen-and-paper' questionnaire. The data generated suggest that the use of toys increased the students' knowledge and confidence statistically significantly (p>0.000 in both cases) with medium (d=0.67) and high (d=0.78) practical significance (effect sizes), respectively. The subject content knowledge and confidence data correlated positively (r=0.69) and, although some caveats and reservations were expressed, the majority of the participating students ascribed their improved knowledge and confidence to the use of toys during the intervention.

This quantitative and qualitative interpretive exploratory case study investigates whether exposure to an Internet based "Extended Cyberhunt" strategy enables teachers to attain a set of outcomes similar to Prensky's "Essential 21st Century Skills" and the "Critical Outcomes of the South African National Curriculum Statement (NCS)". The outcomes referred to include effective planning, designing, decision making and goal setting; improved computer and data searching skills; enhanced confidence, interest, reflective ability, collaboration, judgment and creative and critical thinking; as well as effective problem solving and the ability to communicate and interact with individuals and groups. The Extended Cyberhunt strategy, which focuses on enabling participants to become the designers of questions on curriculum related topics at different cognitive levels of Bloom's "Taxonomy", was introduced to teachers who were first time users of the Internet, Microsoft "Word" and "PowerPoint". The intention was to ascertain these teachers' perceptions of the utility of the strategy in terms of assisting them to implement the critical outcomes described above with school level learners. Data on their perceptions and experiences related to these outcomes were generated and triangulated by means of a pre and post-Likert scale questionnaire, an open ended questionnaire, qualitative semi-structured interviews, reflective journal writing, and implementer reflections. Positive gains were revealed in terms of all of the above outcomes after exposure to the Extended Cyberhunt strategy. These findings are considered in terms of differences between the approach used and traditional teacher-centred teaching, and the strategy is examined using activity theory as a lens. While we are aware that many alternative approaches exist that may be just as successful in terms of attaining the desired outcomes, we believe that the Extended Cyberhunt strategy is both a fruitful extension of "WebQuests" and other existing Internet-based approaches, and a relatively easily implementable and viable way of attaining the desired outcomes. (Contains 1 figure and 1 table.)

This study focuses on Grade 6 learners' perceptions of 'learning as design' during the creation of a collaborative hypermedia product. Data were generated via a Likert Scale questionnaire, semi-structured interviews, learner journals, observational notes, Task Elicitation List, Task Ranking List and open-ended learner evaluation reports. The findings of the study are considered within Lehrer's framework for hyper-composition-based design, i.e. planning, translating and transforming, evaluation and revising. Inferences are made which suggest that a more explicit and comprehensive overview of the process can be presented as an 'extended learning by design' model. This framework or model is visually presented to prospective implementers.

This research study, carried out in South Africa and the United States of America, investigated issues that may hamper prospective primary school teachers from writing acceptable problem posing scenarios involving the addition of fractions. Pre-service teachers (n=44) were asked to compose real life problems involving the addition of two fractions where the sum is greater than one. The data generated suggest that issues that hamper the writing of acceptable problem scenarios are an inability to recognise that uniform units must be used, i.e. that for units to be comparable they must be the same size and shape, that standard/formal units of measurement must be used rather than informal units, and that different units of measurement cannot be used to represent the same fractional part. Another issue is the apparent inability of some students to recognise that the sum of given fractions can be greater than one whole. Finally, the use of colloquial language and local context were considered in terms of posing appropriate word problems involving fractions.

The aim of this paper is to introduce to the education community to a newly developed "Learner Centred Learning-By-Designing Extended Cyberhunts" (LCLBDEC) strategy for teaching and learning in schools. The main focus of the strategy is to enable learners to become designers of an educational tool which assists them to learn during the design process, and also can be used by other learners or students to get a better understanding of a topic. It is suggested that the strategy assists learners to clarify misconceptions that they might have and that it allows them to address aspects in the curriculum when there is not enough time to do so in class. During the initial stages of the strategy, learners are exposed to teacher designed Cyberhunts, a strategy that can be used to introduce learning by design to novices. As the learners become more computer literate, they become the designers instead of the teacher. Learners search for information online on a topic or theme and then are not only required to create questions on as many different cognitive levels as possible, but also to compose a complementing memorandum. The strategy is not meant to be in competition with WebQuests and other similar approaches, but should be seen as an additional information communication and technology (ICT) strategy to complement those that already exist. (Contains 1 table and 3 figures.)

This study investigates the effects of a scientific literacy strategy which focuses on reading, writing, talking and doing science on the development of grade six and seven learners' general literacy skills, both in their home language (isiXhosa) and the language of classroom instruction (English). A mixed method design was used. Quantitative data were generated via baseline and post-testing of learners' language skills and qualitative data were generated by interviews and classroom observation. The sample comprised of seven grade six and seven (multigrade) classes in seven primary schools (five experimental schools and two comparison schools) in the deep rural area of the Tyumie Valley in the Eastern Cape. Mean score differences between the experimental and comparison groups for the reading, writing, listening and speaking aspects of the literacy test were analysed using Analysis of Co-variance (ANCOVA) techniques. Qualitative data generated were used to gain insights into the statistical findings. The data suggest that the scientific literacy strategy statistically significantly improved the learners' reading skills in English, their listening skills in both English and isiXhosa, and their writing in isiXhosa over the course of one academic year.

This study investigates whether the generation of exploratory talk in grade seven, second-language science classrooms in the Eastern Cape Province, South Africa, has a positive effect on learners in terms of their problem-solving and reasoning skills and whether socio-cultural "milieus" (urban, peri-urban and rural settings of schools) have an effect on any cognitive gains that may be made by learners. The findings were that there is a clear and statistically significant improvement in the mean test scores on problem-solving and reasoning of pupils who participated in the classroom discussion initiative (exploratory talk) over those of the comparison groups. This result was consistent in both the first- and second-studies that were undertaken. There was also a significant difference between the gains in problem-solving and reasoning test scores of the three socio-geographical settings in which the participating schools are found.

Ecological case study data were used to determine high school pupils' and university students' ability to organize and use these data to predict outcomes of interaction between populations within a community. The poor quality of answers given by the respondents suggests that explicit teaching, prior to the use of the case study, may greatly enhance its value. (Author)

Investigated is the ability of high school pupils and university students to answer questions based on relationships within food webs using sound ecological principles. Research methods used and the results of this study are discussed. (CW)