Empowering students to perform an enhanced role in the assessment process: Possibilities and challenges

Assessment is key to student learning. This paper examines the case for increased participation by higher education students in the assessment process to deepen learning and improve learner motivation. While increased student participation may not solve all problems relating to assessment, a review of the literature dealing with enhancing the role of students in the assessment process, and original research conducted amongst academics and students at the author\u27s institution, suggests improvements can be made leading to increased student satisfaction, motivation and competency. This paper therefore argues for change in the approach to assessment by empowering students to become partners in the assessment process rather than being mere recipients of grades

The SLD vertex detector upgrade (VXD3) and a study of bbg events

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.This thesis presents a variety of work concerning the design, construction and use of the SLD's vertex detector. SLD's pioneering 120 Mpixel vertex detector, VXD2, was replaced by VXD3, a 307Mpixel CCD vertex detector in January 1996. The motivation for the up-grade detector and its subsquent construction and testing are described in some detail. This work represents the collaborative work of a large number of people. My work was mainly carried out at EEV on the testing of the CCDs and subsequent ladders. VXD3 was commissioned during the 1996 SLD run and performed very close to design specifications. Monitoring the position of VXD3 is crucial for reconstructing the data in the detector for physics analysis. This was carried out using a capacitive wire position monitoring system. The system indicated that VXD3 was very stable during the whole of the 1996 run, except for known controlled movements. VXD3 was aligned globally for each period in-between these known movements using the tracks from e+e- → Z° → hadrons. The structure of three-jet bbg events has been studied using hadronic Z° decays from the 1993-1995 SLD data. Three-jet final states were selected and the CCD-based vertex detector was used to identify two of the jets as a ь or ъ. The distributions of the gluon energy and polar angle with respect to the electron beam direction were examined and were compared with perturbative QCD predictions. If was found that the QCD Parton Shower prediction was needed to describe the data well. These distributions are potentially sensitive to an anomalous b chromomagnetic moment к. к was measured to be -0.031±0.038 0.039(Stat.)±0.003 0.004(Syst.), which is consistent with the Standard Model, with 95% confidence level limit, -0.106 < к < 0.044

Embedding High Definition Videoconferencing in Higher Education to Create Global Graduates

Study abroad programmes designed to meet industry needs for graduates with inter-cultural skills and a global outlook have low participation rates in Canada and Ireland due mainly to financial barriers. Embedding the use of High Definition Interactive Videoconferencing (HD IVC) in higher education has the potential to create ‘Global Graduates’ with the skills sought by employers today. The ‘Global Class’ is a concept which has been developed at Durham College, Canada. Using HD IVC, students from different countries can participate in a ninety-minute class facilitated by Durham College and led by an invited thought leader with expertise in a specific domain. This paper documents the specific experience of first year undergraduate students from the Institute of Technology, Blanchardstown (ITB), Dublin, who participated in a Global Class dealing with business ethics in November 2015. Feedback from a sample of the ITB students who participated in the class is encouraging. It points to an enriched cross-cultural learning environment, suggesting the approach provides a basis for the creation of ‘Global Graduates’. Additional research will serve to further validate the approach and the practicalities of deploying the concept systematically and persistently in course curricula

Single position substitution of hairpin pyrrole-imidazole polyamides imparts distinct DNA-binding profiles across the human genome

Pyrrole–imidazole (Py–Im) polyamides are synthetic molecules that can be rationally designed to target specific DNA sequences to both disrupt and recruit transcriptional machinery. While in vitro binding has been extensively studied, in vivo effects are often difficult to predict using current models of DNA binding. Determining the impact of genomic architecture and the local chromatin landscape on polyamide-DNA sequence specificity remains an unresolved question that impedes their effective deployment in vivo. In this report we identified polyamide–DNA interaction sites across the entire genome, by covalently crosslinking and capturing these events in the nuclei of human LNCaP cells. This technique confirms the ability of two eight ring hairpin-polyamides, with similar architectures but differing at a single ring position (Py to Im), to retain in vitro specificities and display distinct genome-wide binding profiles

Single position substitution of hairpin pyrrole-imidazole polyamides imparts distinct DNA-binding profiles across the human genome

Pyrrole–imidazole (Py–Im) polyamides are synthetic molecules that can be rationally designed to target specific DNA sequences to both disrupt and recruit transcriptional machinery. While in vitro binding has been extensively studied, in vivo effects are often difficult to predict using current models of DNA binding. Determining the impact of genomic architecture and the local chromatin landscape on polyamide-DNA sequence specificity remains an unresolved question that impedes their effective deployment in vivo. In this report we identified polyamide–DNA interaction sites across the entire genome, by covalently crosslinking and capturing these events in the nuclei of human LNCaP cells. This technique confirms the ability of two eight ring hairpin-polyamides, with similar architectures but differing at a single ring position (Py to Im), to retain in vitro specificities and display distinct genome-wide binding profiles

Recognition of the Minor Groove of DNA by Hairpin Polyamides Containing α-Substituted-β-Amino Acids

Incorporation of the flexible amino acid β-alanine (β) into hairpin polyamides composed of N-methylpyrrole (Py) and N-methylimidazole (Im) amino acids is required for binding to DNA sequences longer than seven base pairs with high affinity and sequence selectivity. Pairing the α-substituted-β-amino acids (S)-isoserine (^SIs), (R)-isoserine (^RIs), β-aminoalanine (Aa), and α-fluoro-β-alanine (Fb) side-by-side with β in hairpin polyamides alters DNA binding affinity and selectivity relative to the parent polyamide containing a β/β pairing. Quantitative DNase I footprinting titration studies on a restriction fragment containing the sequences 5‘-TGCNGTA-3‘ (N = A, T, G, and C) show that the polyamide ImPy^SIsImPy-γ-PyPyβImPy-β-Dp (^SIs/β pairing) binds to N = T (K_a = 4.5 × 10^9 M^(-1)) in preference to N = A (K_a = 6.2 × 10^8 M^(-1)). This result stands in contrast to the essentially degenerate binding of the parent ImPyβImPy-γ-PyPyβImPy-β-Dp (β/β pairing) to N = T and N = A, and to the slight preference of ImPyβImPy-γ-PyPy^SIsImPy-β-Dp (β/^SIs pairing) to N = A over N = T. Additionally, this study reveals that incorporation of ^RIs, Aa, and Fb into polyamides significantly reduces binding affinity. Therefore, DNA binding in the minor groove is sensitive to the stereochemistry, steric bulk, and electronics of the substituent at the α-position of β-amino acids in hairpin polyamides containing β/β pairs

Integrative network modeling reveals mechanisms underlying T cell exhaustion.

Failure to clear antigens causes CD8+ T cells to become increasingly hypo-functional, a state known as exhaustion. We combined manually extracted information from published literature with gene expression data from diverse model systems to infer a set of molecular regulatory interactions that underpin exhaustion. Topological analysis and simulation modeling of the network suggests CD8+ T cells undergo 2 major transitions in state following stimulation. The time cells spend in the earlier pro-memory/proliferative (PP) state is a fixed and inherent property of the network structure. Transition to the second state is necessary for exhaustion. Combining insights from network topology analysis and simulation modeling, we predict the extent to which each node in our network drives cells towards an exhausted state. We demonstrate the utility of our approach by experimentally testing the prediction that drug-induced interference with EZH2 function increases the proportion of pro-memory/proliferative cells in the early days post-activation

Rapid DNA mapping by fluorescent single molecule detection

DNA mapping is an important analytical tool in genomic sequencing, medical diagnostics and pathogen identification. Here we report an optical DNA mapping strategy based on direct imaging of individual DNA molecules and localization of multiple sequence motifs on the molecules. Individual genomic DNA molecules were labeled with fluorescent dyes at specific sequence motifs by the action of nicking endonuclease followed by the incorporation of dye terminators with DNA polymerase. The labeled DNA molecules were then stretched into linear form on a modified glass surface and imaged using total internal reflection fluorescence (TIRF) microscopy. By determining the positions of the fluorescent labels with respect to the DNA backbone, the distribution of the sequence motif recognized by the nicking endonuclease can be established with good accuracy, in a manner similar to reading a barcode. With this approach, we constructed a specific sequence motif map of lambda-DNA. We further demonstrated the capability of this approach to rapidly type a human adenovirus and several strains of human rhinovirus

Sequence-specific DNA cleavage mediated by bipyridine polyamide conjugates

The design of molecules that damage a selected DNA sequence provides a formidable opportunity for basic and applied biology. For example, such molecules offer new prospects for controlled manipulation of the genome. The conjugation of DNA-code reading molecules such as polyamides to reagents that induce DNA damages provides an approach to reach this goal. In this work, we showed that a bipyridine conjugate of polyamides was able to induce sequence-specific DNA breaks in cells. We synthesized compounds based on two polyamide parts linked to bipyridine at different positions. Bipyridine conjugates of polyamides were found to have a high affinity for the DNA target and one of them produced a specific and high-yield cleavage in vitro and in cultured cells. The bipyridine conjugate studied here, also presents cell penetrating properties since it is active when directly added to cell culture medium. Harnessing DNA damaging molecules such as bipyridine to predetermined genomic sites, as achieved here, provides an attractive strategy for targeted genome modification and DNA repair studies

Direct inhibition of the DNA-binding activity of POU transcription factors Pit-1 and Brn-3 by selective binding of a phenyl-furan-benzimidazole dication

The development of small molecules to control gene expression could be the spearhead of future-targeted therapeutic approaches in multiple pathologies. Among heterocyclic dications developed with this aim, a phenyl-furan-benzimidazole dication DB293 binds AT-rich sites as a monomer and 5′-ATGA sequence as a stacked dimer, both in the minor groove. Here, we used a protein/DNA array approach to evaluate the ability of DB293 to specifically inhibit transcription factors DNA-binding in a single-step, competitive mode. DB293 inhibits two POU-domain transcription factors Pit-1 and Brn-3 but not IRF-1, despite the presence of an ATGA and AT-rich sites within all three consensus sequences. EMSA, DNase I footprinting and surface-plasmon-resonance experiments determined the precise binding site, affinity and stoichiometry of DB293 interaction to the consensus targets. Binding of DB293 occurred as a cooperative dimer on the ATGA part of Brn-3 site but as two monomers on AT-rich sites of IRF-1 sequence. For Pit-1 site, ATGA or AT-rich mutated sequences identified the contribution of both sites for DB293 recognition. In conclusion, DB293 is a strong inhibitor of two POU-domain transcription factors through a cooperative binding to ATGA. These findings are the first to show that heterocyclic dications can inhibit major groove transcription factors and they open the door to the control of transcription factors activity by those compounds