Double-strand breaks and the concept of short- and long-term epigenetic memory

Double-strand breaks represent an extremely cytolethal form of DNA damage and thus pose a serious threat to the preservation of genetic and epigenetic information. Though it is well-known that double-strand breaks such as those generated by ionising radiation are among the principal causative factors behind mutations, chromosomal aberrations, genetic instability and carcino-genesis, significantly less is known about the epigenetic consequences of double-strand break formation and repair for carcinogenesis. Double-strand break repair is a highly coordinated process that requires the unravelling of the compacted chromatin structure to facilitate repair machinery access and then restoration of the original undamaged chromatin state. Recent experimental findings have pointed to a potential mechanism for double-strand break-induced epigenetic silencing. This review will discuss some of the key epigenetic regulatory processes involved in double-strand break (DSB) repair and how incomplete or incorrect restoration of chromatin structure can leave a DSB-induced epigenetic memory of damage with potentially pathological repercussions

Memory management and parallelization of data intensive all-to-all comparison in shared-memory systems

This thesis presents a novel program parallelization technique incorporating with dynamic and static scheduling. It utilizes a problem specific pattern developed from the prior knowledge of the targeted problem abstraction. Suitable for solving complex parallelization problems such as data intensive all-to-all comparison constrained by memory, the technique delivers more robust and faster task scheduling compared to the state-of-the art techniques. Good performance is achieved from the technique in data intensive bioinformatics applications.

In-memory business process management

In-memory databases have become a mainstay of enterprise computing offering significant performance and scalability boosts for online analytical and (to a lesser extent) transactional processing as well as improved prospects for integration across different applications through an efficient shared database layer. Significant research and development has been undertaken over several years concerning data management considerations of in-memory databases. However, limited insights are available on the impacts of applications and their supportive middleware platforms and how they need to evolve to fully function through, and leverage, in-memory database capabilities. This paper provides a first, comprehensive exposition into how in-memory databases impact Business Pro- cess Management, as a mission-critical and exemplary model-driven integration and orchestration middleware. Through it, we argue that in-memory databases will render some prevalent uses of legacy BPM middleware obsolete, but also open up exciting possibilities for tighter application integration, better process automation performance and some entirely new BPM capabilities such as process-based application customization. To validate the feasibility of an in-memory BPM, we develop a surprisingly simple BPM runtime embedded into SAP HANA and providing for BPMN-based process automation capabilities.

Patterns of boardroom discussions around the accountability process in a nonprofit organisation

This chapter sets out to identify patterns at play in boardroom discussions around the design and adoption of an accountability system in a nonprofit organisation. To this end, it contributes to the scarce literature showing the backstage of management accounting systems (Berry, 2005), investment policy determining (Kreander, Beattie & McPhail, 2009; Kreander, McPhail & Molyneaux, 2004) and financial planning strategizing (Parker, 2004) or budgeting (Irvine 2005). The paucity of publications is due to issues raised by confidentiality preventing attendance at those meetings (Irvine, 2003), Irvine & Gaffikin, 2006). However, often, the implementation of a new control technology occurs over a long period of time that might exceed the duration of a research project (Quattrone & Hopper, 2001, 2005). Recent trends consisting of having research funded by grants from private institutions or charities have tended to reduce the length of such undertakings to a few months or rarely more than a couple of years (Parker, 2013);

Temporal and spatial patterns of seed dispersal of Musa acuminata by Cynopterus sphinx

The foraging behavior of greater short-nosed fruit bats (Cynopterus sphinx) on wild banana (Musa acuminata) and subsequent dispersal of seeds were studied in the Tropical Rainforest Conservation Area, Xishuangbanna Tropical Botanical Garden, Yunnan province, by direct observation of marked fruits, mist netting, and seed collection. The mean number (± SE) of individual C. sphinx captured by mist net were 2.2 ± 0.33/day and 1.4 ± 0.32/day in the rainy season (September to October) and dry season (November to December), respectively; the difference was not significant. The number of seed pellets expelled was 9.0 ± 1.12/day and 7.2 ± 1.37/day in the rainy and dry seasons respectively; again the difference was not significant. The removal curves for marked fruit were similar for 10 focal trees. Fruits were consumed heavily within two weeks after ripening and all the marked fruit were removed within one month. The difference in seed dispersal was significant between different feeding roosts indicating that patterns of seed dispersal may not be uniform. We found the seeds of M. acuminata can be dispersed by C. sphinx to a distance of about 200 m, and C. sphinx can be considered as an effective seed disperser of M. acuminata.

The Scent of Ancestral Memory

Poetry expresses the physical and spiritual worlds that other kinds of writing cannot. Travelling open our minds and frees our spirit. Creative writings and meditations on life, spirit, grace and relationships, art and nature weave their way through these lyrical poems. Some poems are suitable for study in the Australian Curriculum.

Using extended random set to find specific patterns

With the overwhelming increase in the amount of data on the web and data bases, many text mining techniques have been proposed for mining useful patterns in text documents. Extracting closed sequential patterns using the Pattern Taxonomy Model (PTM) is one of the pruning methods to remove noisy, inconsistent, and redundant patterns. However, PTM model treats each extracted pattern as whole without considering included terms, which could affect the quality of extracted patterns. This paper propose an innovative and effective method that extends the random set to accurately weigh patterns based on their distribution in the documents and their terms distribution in patterns. Then, the proposed approach will find the specific closed sequential patterns (SCSP) based on the new calculated weight. The experimental results on Reuters Corpus Volume 1 (RCV1) data collection and TREC topics show that the proposed method significantly outperforms other state-of-the-art methods in different popular measures.

Interpreting discovered patterns in terms of ontology concepts

Semantic Web offers many possibilities for future Web technologies. Therefore, it is a need to search for ways that can bring the huge amount of unstructured documents from current Web to Semantic Web automatically. One big challenge in searching for such ways is how to understand patterns by both humans and machine. To address this issue, we present an innovative model which interprets patterns to high level concepts. These concepts can explain the patterns' meanings in a human understandable way while improving the information filtering performance. The model is evaluated by comparing it against one state-of-the-art benchmark model using standard Reuters dataset. The results show that the proposed model is successful. The significance of this model is three fold. It gives a way to interpret text mining output, provides a technique to find concepts relevant to the whole set of patterns which is an essential feature to understand the topic, and to some extent overcomes information mismatch and overload problems of existing models. This model will be very useful for knowledge based applications.

The role of δ-opioid receptors in learning and memory underlying the development of addiction

Opioids are important endogenous ligands that exist in both invertebrates and vertebrates and signal by activation of opioid receptors to produce analgesia and reward or pleasure. The μ-opioid receptor is the best known of the opioid receptors and mediates the acute analgesic effects of opiates, while the δ-opioid receptor (DOR) has been less well studied and has been linked to effects that follow from chronic use of opiates such as stress, inflammation and anxiety. Recently, DORs have been shown to play an essential role in emotions and increasing evidence points to a role in learning actions and outcomes. The process of learning and memory in addiction has been proposed to involve strengthening of specific brain circuits when a drug is paired with a context or environment. The DOR is highly expressed in the hippocampus, amygdala, striatum and other basal ganglia structures known to participate in learning and memory. In this review, we will focus on the role of the DOR and its potential role in learning and memory underlying the development of addiction.

Methotrexate-conjugated PEGylated dendrimers show differential patterns of deposition and activity in tumour-burdened lymph nodes after intravenous and subcutaneous administration in rats

The current study sought to explore whether the subcutaneous administration of lymph-targeted dendrimers, conjugated with a model chemotherapeutic (methotrexate, MTX), was able to enhance anticancer activity against lymph node metastases. The lymphatic pharmacokinetics and antitumour activity of PEGylated polylysine dendrimers conjugated to MTX [D-MTX(OH)] via a tumour-labile hexapeptide linker was examined in rats and compared to a similar system where MTX was α-carboxyl O-tert-butylated [D-MTX(OtBu)]. The latter has previously been shown to exhibit longer plasma circulation times. D-MTX(OtBu) was well absorbed from the subcutaneous injection site via the lymph, and 3 to 4%/g of the dose was retained by sentinel lymph nodes. In contrast, D-MTX(OH) showed limited absorption from the subcutaneous injection site, but absorption was almost exclusively via the lymph. The retention of D-MTX(OH) by sentinel lymph nodes was also significantly elevated (approximately 30% dose/g). MTX alone was not absorbed into the lymph. All dendrimers displayed lower lymph node targeting after intravenous administration. Despite significant differences in the lymph node retention of D-MTX(OH) and D-MTX(OtBu) after subcutaneous and intravenous administration, the growth of lymph node metastases was similarly inhibited. In contrast, the administration of MTX alone did not significantly reduce lymph node tumour growth. Subcutaneous administration of drug-conjugated dendrimers therefore provides an opportunity to improve drug deposition in downstream tumour-burdened lymph nodes. In this case, however, increased lymph node biodistribution did not correlate well with antitumour activity, possibly suggesting constrained drug release at the site of action.

Teaching Reflective Learning in Higher Education : A Systematic Approach Using Pedagogic Patterns

This book is about understanding the nature and application of reflection in higher education. It provides a theoretical model to guide the implementation of reflective learning and reflective practice across multiple disciplines and international contexts in higher education. The book presents research into the ways in which reflection is both considered and implemented in different ways across different professional disciplines, while maintaining a common purpose to transform and improve learning and/or practice. Readers will find this book innovative and new in three key ways. First, in its holistic theorisation of reflection within the pedagogic field of higher education; Secondly, in conceptualising reflection in different modes to achieve specific purposes in different disciplines; and finally, in providing conceptual guidance for embedding reflective learning and reflective practice in a systematic way across whole programmes, faculties or institutions in higher education. The book considers important contextual factors that influence the teaching of forms and methods of reflection. It provides a functional analysis of multiple modes of reflection, including written, oral, visual, auditory, and embodied forms. Empirical chapters analyse the application of these modes across disciplines and at different stages of a programme. The theoretical model accounts for students’ stage of development in the disciplinary field, along with progressive and cyclical levels of higher order thinking, and learning and professional practice that are expected within different disciplines and professional fields. The book provides: • A conceptual model for the application of reflection across disciplines in a variety of contexts. • Empirical examples of different modes and pedagogic patterns for reflection. • Guidance and support for embedding systemic pedagogical and curriculum change.

Patterns of service use among persons with Schizophrenia and other psychotic disorders

Objective: This study assessed 12-month service use patterns among people with psychotic disorders and sought to identify determinants of service use. Methods: As part of a large two-phase Australian study of psychotic disorders, structured interviews were conducted with a stratified random sample of adults who screened positive for psychosis. Demographic characteristics, social functioning, symptoms, mental health diagnoses, and use of psychiatric and nonpsychiatric services were assessed. Data were analyzed for 858 persons who had an ICD-10 diagnosis of a psychotic disorder and who had been hospitalized for less than six months during the previous year. Results: People with psychotic disorders had high levels of use of health services, both in absolute terms and relative to people with nonpsychotic disorders. Those with psychotic disorders were estimated to have an average of one contact with health services per week. Use of psychiatric inpatient services was associated with parenthood, higher symptom levels, recent attempts at suicide or self-harm, personal disability, medication status, and frequency of alcohol consumption. Services provided by general practitioners (family physicians) were more likely to be obtained by older people, women, people with greater availability of friends, those with fewer negative symptoms, and those whose service needs were unmet by other sources. People who were high users of health services also reported having more contact with a range of non-health agencies. Conclusions: The predictors of service use accounted for small proportions of the variance in overall use of health services. The role of general practitioners in providing and monitoring treatment programs and other psychosocial interventions needs to be acknowledged and enhanced.

Large Scale Simulations of Hippocampal-Neocortical Interactions in a Parallel Version of Genesis

A hippocampal-CA3 memory model was constructed with PGENESIS, a recently developed version of GENESIS that allows for distributed processing of a neural network simulation. A number of neural models of the human memory system have identified the CA3 region of the hippocampus as storing the declarative memory trace. However, computational models designed to assess the viability of the putative mechanisms of storage and retrieval have generally been too abstract to allow comparison with empirical data. Recent experimental evidence has shown that selective knock-out of NMDA receptors in the CA1 of mice leads to reduced stability of firing specificity in place cells. Here a similar reduction of stability of input specificity is demonstrated in a biologically plausible neural network model of the CA3 region, under conditions of Hebbian synaptic plasticity versus an absence of plasticity. The CA3 region is also commonly associated with seizure activity. Further simulations of the same model tested the response to continuously repeating versus randomized nonrepeating input patterns. Each paradigm delivered input of equal intensity and duration. Non-repeating input patterns elicited a greater pyramidal cell spike count. This suggests that repetitive versus non-repeating neocortical inpus has a quantitatively different effect on the hippocampus. This may be relevant to the production of independent epileptogenic zones and the process of encoding new memories.