Feedback regulation by Atf3 in the endothelin-1-responsive transcriptome of cardiomyocytes: Egr1 is a principal Atf3 target

Endothelin-1 promotes cardiomyocyte hypertrophy by inducing changes in gene expression. Immediate early genes including activating transcription factor 3 (Atf3), Egr1 and Ptgs2 are rapidly and transiently upregulated by endothelin-1 in cardiomyocytes. Atf3 regulates expression of downstream genes and is implicated in negative feedback regulation of other immediate early genes. To identify Atf3-regulated genes, we knocked down Atf3 expression in cardiomyocytes exposed to endothelin-1 and used microarrays to interrogate the transcriptomic effects. Of upregulated mRNAs, expression of 23 (including Egr1, Ptgs2) was enhanced and expression of 25 was inhibited by Atf3 knockdown. Using quantitative PCR, we determined that knockdown of Atf3 had little effect on upregulation of Egr1 mRNA over 30 min, but abolished the subsequent decline, causing sustained Egr1 mRNA expression and enhanced protein expression. This resulted from direct binding of Atf3 to the Egr1 promoter. Mathematical modelling established that Atf3 can suffice to suppress Egr1 expression. Given the widespread co-regulation of Atf3 with Egr1, we suggest that the Atf3-Egr1 negative feedback loop is of general significance. Loss of Atf3 caused abnormal cardiomyocyte growth, presumably resulting from dysregulation of target genes. Our data therefore identify Atf3 as a nexus in cardiomyocyte hypertrophy required to facilitate the full and proper growth response.

New evidence from Southern Jordan: rethinking the role of architecture in changing societies at the beginning of the Neolithic process

The development of architecture and the settlement is central to discussions concerning the Neolithic transformation asthe very visible evidence for the changes in society that run parallel to the domestication of plants and animals. Architecture hasbeen used as an important aspect of models of how the transformation occurred, and as evidence for the sharp difference betweenhunter-gatherer and farming societies. We suggest that the emerging evidence for considerable architectural complexity from theearly Neolithic indicates that some of our interpretations depend too much on a very basic understanding of structures which arenormally seen as being primarily for residential purposes and containing households, which become the organising principle for thenew communities which are often seen as fully sedentary and described as villages. Recent work in southern Jordan suggests that inthis region at least there is little evidence for a standard house, and that structures are constructed for a range of diverse primary purposes other than simple domestic shelters.

Architecture, sedentism, and social complexity at Pre-Pottery Neolithic A WF16, Southern Jordan

Recent excavations at Pre-Pottery Neolithic A (PPNA) WF16 in southern Jordan have revealed remarkable evidence of architectural developments in the early Neolithic. This sheds light on both special purpose structures and “domestic” settlement, allowing fresh insights into the development of increasingly sedentary communities and the social systems they supported. The development of sedentary communities is a central part of the Neolithic process in Southwest Asia. Architecture and ideas of homes and households have been important to the debate, although there has also been considerable discussion on the role of communal buildings and the organization of early sedentarizing communities since the discovery of the tower at Jericho. Recently, the focus has been on either northern Levantine PPNA sites, such as Jerf el Ahmar, or the emergence of ritual buildings in the Pre-Pottery Neolithic B of the southern Levant. Much of the debate revolves around a division between what is interpreted as domestic space, contrasted with “special purpose” buildings. Our recent evidence allows a fresh examination of the nature of early Neolithic communities.

Gibberellin-responsive and -insensitive dwarfing alleles on wheat performance in contrasting tillage systems

Near-isogenic lines (NILs) of winter wheat varying for alleles for reduced height (Rht), gibberellin (GA) response and photoperiod insensitivity (Ppd-D1a) in cv. Mercia background (rht (tall), Rht-B1b, Rht-D1b, Rht-B1c, Rht8c+Ppd-D1a, Rht-D1c, Rht12) and cv. Maris Widgeon (rht (tall), Rht-D1b, Rht-B1c) backgrounds were compared to investigate main effects and interactions with tillage (plough-based, minimum-, and zero-tillage) over two years. Both minimum- and zero- tillage were associated with reduced grain yields allied to reduced harvest index, biomass accumulation, interception of photosynthetically active radiation (PAR), and plant populations. Grain yields were optimized at mature crop heights of around 740mm because this provided the best compromise between harvest index which declined with height, and above ground biomass which increased with height. Improving biomass with height was due to improvements in both PAR interception and radiation-use efficiency. Optimum height for grain yield was unaffected by tillage system or GA-sensitivity. After accounting for effects of height, GA insensitivity was associated with increased grain yields due to increased grains per spike, which was more than enough to compensate for poorer plant establishment and lower mean grain weights compared to the GA-sensitive lines. Although better establishment was possible with GA-sensitive lines, there was no evidence that this effect interacted with tillage method. We find, therefore, little evidence to question the current adoption of wheats with reduced sensitivity to GA in the UK, even as tillage intensity lessens.

Formation of vesicles through solvent assisted self-assembly of hydrophobic pentapeptides: encapsulation and pH responsive release of dyes by the vesicles

In the biomimetic design two hydrophobic pentapetides Boc-Ile-Aib-Leu-Phe-Ala-OMe ( I) and Boc-Gly-Ile-Aib-Leu-Phe-OMe (II) (Aib: alpha-aminoisobutyric acid) containing one Aib each are found to undergo solvent assisted self-assembly in methanol/water to form vesicular structures, which can be disrupted by simple addition of acid. The nanovesicles are found to encapsulate dye molecules that can be released by the addition of acid as confirmed by fluorescence microscopy and UV studies. The influence of solvent polarity on the morphology of the materials generated from the peptides has been examined systematically, and shows that fibrillar structures are formed in less polar chloroform/petroleum ether mixture and vesicular structures are formed in more polar methanol/water. Single crystal X-ray diffraction studies reveal that while beta-sheet mediated self-assembly leads to the formation of fibrillar structures, the solvated beta-sheet structure leads to the formation of vesicular structures. The results demonstrate that even hydrophobic peptides can generate vesicular structures from polar solvent which may be employed in model studies of complex biological phenomena.

Salts responsive nanovesicles through π-stacking induced self-assembly of backbone modified tripeptides

A set of backbone modified peptides of general formula Boc-Xx-m-ABA-Yy-OMe where m-ABA is meta-aminobenzoic acid and Xx and Yy are natural amino acids such as Phe, Gly, Pro, Leu, Ile, Tyr and Trp etc., are found to self-assemble into soft nanovesicular structures in methanol-water solution (9:1 by v/v). At higher concentration the peptides generate larger vesicles which are formed through fusion of smaller vesicles. The formation of vesicles has been facilitated through the participation of various noncovalent interactions such as aromatic pi-stacking, hydrogen bonding and hydrophobic interactions. Model study indicates that the pi-stacking induced self-assembly, mediated by m-ABA is essential for well structured vesicles formation. The presence of conformationally rigid m-ABA in the backbone of the peptides also helps to form vesicular structures by restricting the conformational entropy. The vesicular structures get disrupted in presence of various salts such as KCl, CaCl(2), N(n-Bu)(4)Br and (NH(4))(2)SO(4) in methanol-water solution. Fluorescence microscopy and UV studies reveal that the soft nanovesicles encapsulate organic dye molecules such as Rhodamine B and Acridine Orange which could be released through salts induced disruption of vesicles.

An organisational semiotics inspired information architecture: pervasive healthcare as a case study

Information architecture (IA) is defined as high level information requirements of an organisation. It is applied in areas such as information systems development, enterprise architecture, business processes management and organisational change management. Still, the lack of methods and theories prevents information architecture becoming a distinct discipline. Healthcare organisation is always seen as information intensive organisation, moreover in a pervasive healthcare environment. Pervasive healthcare aims to provide healthcare services to anyone, anywhere and anytime by incorporating mobile devices and wireless network. Information architecture hence plays an important role in information provisioning within the context of pervasive healthcare in order to support decision making and communication between clinician and patients. Organisational semiotics is one of the social technical approaches that contemplate information through the norms or activities performed within an organisation prior to pervasive healthcare implementation. This paper proposes a conceptual design of information architecture for pervasive healthcare. It is illustrated with a scenario of mental health patient monitoring.

Parallel pipelined histogram architecture via c-slow retiming

A parallel pipelined array of cells suitable for realtime computation of histograms is proposed. The cell architecture builds on previous work to now allow operating on a stream of data at 1 pixel per clock cycle. This new cell is more suitable for interfacing to camera sensors or to microprocessors of 8-bit data buses which are common in consumer digital cameras. Arrays using the new proposed cells are obtained via C-slow retiming techniques and can be clocked at a 65% faster frequency than previous arrays. This achieves over 80% of the performance of two-pixel per clock cycle parallel pipelined arrays.

A parallel quantum histogram architecture

A parallel formulation of an algorithm for the histogram computation of n data items using an on-the-fly data decomposition and a novel quantum-like representation (QR) is developed. The QR transformation separates multiple data read operations from multiple bin update operations thereby making it easier to bind data items into their corresponding histogram bins. Under this model the steps required to compute the histogram is n/s + t steps, where s is a speedup factor and t is associated with pipeline latency. Here, we show that an overall speedup factor, s, is available for up to an eightfold acceleration. Our evaluation also shows that each one of these cells requires less area/time complexity compared to similar proposals found in the literature.

Modeling requirement driven architecture of adaptive healthcare system based on semiotics

In order to improve the quality of healthcare services, the integrated large-scale medical information system is needed to adapt to the changing medical environment. In this paper, we propose a requirement driven architecture of healthcare information system with hierarchical architecture. The system operates through the mapping mechanism between these layers and thus can organize functions dynamically adapting to user’s requirement. Furthermore, we introduce the organizational semiotics methods to capture and analyze user’s requirement through ontology chart and norms. Based on these results, the structure of user’s requirement pattern (URP) is established as the driven factor of our system. Our research makes a contribution to design architecture of healthcare system which can adapt to the changing medical environment.

Integrated clinical pathway management for medical quality improvement-based on a semiotically inspired systems architecture

Clinical pathway is an approach to standardise care processes to support the implementations of clinical guidelines and protocols. It is designed to support the management of treatment processes including clinical and non-clinical activities, resources and also financial aspects. It provides detailed guidance for each stage in the management of a patient with the aim of improving the continuity and coordination of care across different disciplines and sectors. However, in the practical treatment process, the lack of knowledge sharing and information accuracy of paper-based clinical pathways burden health-care staff with a large amount of paper work. This will often result in medical errors, inefficient treatment process and thus poor quality medical services. This paper first presents a theoretical underpinning and a co-design research methodology for integrated pathway management by drawing input from organisational semiotics. An approach to integrated clinical pathway management is then proposed, which aims to embed pathway knowledge into treatment processes and existing hospital information systems. The capability of this approach has been demonstrated through the case study in one of the largest hospitals in China. The outcome reveals that medical quality can be improved significantly by the classified clinical pathway knowledge and seamless integration with hospital information systems.

Direct evidence for attention-dependent influences of the frontal eye-fields on feature-responsive visual cortex

Voluntary selective attention can prioritize different features in a visual scene. The frontal eye-fields (FEF) are one potential source of such feature-specific top-down signals, but causal evidence for influences on visual cortex (as was shown for "spatial" attention) has remained elusive. Here, we show that transcranial magnetic stimulation (TMS) applied to right FEF increased the blood oxygen level-dependent (BOLD) signals in visual areas processing "target feature" but not in "distracter feature"-processing regions. TMS-induced BOLD signals increase in motion-responsive visual cortex (MT+) when motion was attended in a display with moving dots superimposed on face stimuli, but in face-responsive fusiform area (FFA) when faces were attended to. These TMS effects on BOLD signal in both regions were negatively related to performance (on the motion task), supporting the behavioral relevance of this pathway. Our findings provide new causal evidence for the human FEF in the control of nonspatial "feature"-based attention, mediated by dynamic influences on feature-specific visual cortex that vary with the currently attended property.

Portfolio advertising as an instrument to strengthen the corporate brand in a complex brand architecture

In recent years, the importance of the corporate brand has significantly grown and companies increasingly seek to strengthen their corporate brand. The corporate brand image can be strengthened through portfolio advertising as a technique of impression management. This mechanism works only if important variables are considered, such as the fit between product brands, the number of product brands as well as the processing depth of the consumers. Based on three experiments, the benefits of portfolio advertising for the corporate brand and its product brands are shown and practical implications are discussed.