Peptide mass fingerprinting using field-programmable gate arrays

The reconfigurable computing paradigm, which exploits the flexibility and versatility of field-programmable gate arrays (FPGAs), has emerged as a powerful solution for speeding up time-critical algorithms. This paper describes a reconfigurable computing solution for processing raw mass spectrometric data generated by MALDI-TOF instruments. The hardware-implemented algorithms for denoising, baseline correction, peak identification, and deisotoping, running on a Xilinx Virtex-2 FPGA at 180 MHz, generate a mass fingerprint that is over 100 times faster than an equivalent algorithm written in C, running on a Dual 3-GHz Xeon server. The results obtained using the FPGA implementation are virtually identical to those generated by a commercial software package MassLynx

Virtual Werribee : a planning support tool

Virtual Werribee is collaborative research in applying 3-D modelling and visualisation as a planning support tool in comparison to 2-D plans and drawings. It was a joint initiative involving Deakin University and the Wyndham City Council to demonstrate the use of 3-D visualisation for planning process in the actual context of a planning authority in Australia. The objective of this project was to assist the council in preparing for the revised Local Structure Plan. By reconstructing the council&rsquo;s data into easily understood information, 3-D model and visualisation served as a verification and discussion tool for decision making. The integration of wider site context also provided a better understanding of the surrounding development areas. This could equip other stakeholders as well as the community to participate in council&rsquo;s planning agenda activities, such as increasing the urban density and building heights limit.Virtual Werribee included the development planning agenda, categorised as new, re-development and hypothetical. The modelling process progressed with sufficient data from the council. Some changes to the initial plan were made, including the use of CAD modelling software instead of GIS software, and production of a block model with selected detail buildings, instead of a full draped 3-D model. The council decided that the block model would be sufficient for their planning purposes. This was determined while taking into consideration the available facilities at the council.The potentials of the model as a planning tool were demonstrated in this paper, and further compared to the council&rsquo;s existing materials prepared by the project developers. The advantages of the 3-D interactive model and visualisation over the conventional materials have provided the council officer with a tool for better empowerment in the planning process. This was also evident in the increasing engagement level between the officer and the model as the process developed. As a result of this, the project scope has also expanded, finally covering the entire city.While Virtual Werribee has the potential to better communicate council&rsquo;s planning agendas to the stakeholders and the community, the key factor, coupled with its visualisation components, was its interactive capability. Property layers with aerial site image that provided a realistic background served as a virtual city platform for different users. Although limited in its analytic capability found in GIS software, this model offered high visualisation content to assist visual impact assessment through its interactive mode along with a series of still images and a simulation movie.<br /

MEME-LaB : motif analysis in clusters

Genome-wide expression analysis can result in large numbers of clusters of co-expressed genes. While there are tools for ab initio discovery of transcription factor binding sites, most do not provide a quick and easy way to study large numbers of clusters. To address this, we introduce a web-tool called MEME-LaB. The tool wraps MEME (an ab initio motif finder), providing an interface for users to input multiple gene clusters, retrieve promoter sequences, run motif finding, and then easily browse and condense the results, facilitating better interpretation of the results from large-scale datasets

Galectin-3 interacts with the cell surface glycoprotein CD146 (MCAM, MUC18) and induces secretion of metastasis-promoting cytokines from vascular endothelial cells

The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans. We have shown previously that circulating galectin-3, which is increased up to 30-fold in cancer patients, promotes blood-borne metastasis in an animal cancer model. This effect is partly attributable to the interaction of galectin-3 with unknown receptor(s) on vascular endothelial cells and causes endothelial secretion of several metastasis-promoting cytokines. Here we sought to identify the galectin-3-binding molecule(s) on the endothelial cell surface responsible for the galectin-3-mediated cytokine secretion. Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells. CD146 was the major galectin-3-binding ligand and strongly co-localized with galectin-3 on endothelial cell surfaces treated with exogenous galectin-3. Moreover, galectin-3 bound to N-linked glycans on CD146 and induced CD146 dimerization and subsequent activation of AKT signaling. siRNA-mediated suppression of CD146 expression completely abolished the galectin-3-induced secretion of IL-6 and G-CSF cytokines from the endothelial cells. Thus, CD146/MCAM is the functional galectin-3-binding ligand on endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines. We conclude that CD146/MCAM interactions with circulating galectin-3 may have an important influence on cancer progression and metastasis

Conserved noncoding sequences highlight shared components of regulatory networks in dicotyledonous plants

Conserved noncoding sequences (CNSs) in DNA are reliable pointers to regulatory elements controlling gene expression. Using a comparative genomics approach with four dicotyledonous plant species (Arabidopsis thaliana, papaya [Carica papaya], poplar [Populus trichocarpa], and grape [Vitis vinifera]), we detected hundreds of CNSs upstream of Arabidopsis genes. Distinct positioning, length, and enrichment for transcription factor binding sites suggest these CNSs play a functional role in transcriptional regulation. The enrichment of transcription factors within the set of genes associated with CNS is consistent with the hypothesis that together they form part of a conserved transcriptional network whose function is to regulate other transcription factors and control development. We identified a set of promoters where regulatory mechanisms are likely to be shared between the model organism Arabidopsis and other dicots, providing areas of focus for further research

On the poverty of a priorism: technology, surveillance in the workplace and employee responses

Many debates about surveillance at work are framed by a set of a priori assumptions about the nature of the employment relationship that inhibits efforts to understand the complexity of employee responses to the spread of new technology at work. In particular, the debate about the prevalence of resistance is hamstrung from the outset by the assumption that all apparently non-compliant acts, whether intentional or not, are to be counted as acts of resistance. Against this background this paper seeks to redress the balance by reviewing results from an ethnographic study of surveillance-capable technologies in a number of British workplaces. It argues for greater attention to be paid to the empirical character of the social relations at work in and through which technologies are deployed and in the context of which employee responses are played out

Direct characterization of the native structure and mechanics of cyanobacterial carboxysomes

Carboxysomes are proteinaceous organelles that play essential roles in enhancing carbon fixation in cyanobacteria and some proteobacteria. These self-assembling organelles encapsulate Ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) and carbonic anhydrase using a protein shell structurally resembling an icosahedral viral capsid. The protein shell serves as a physical barrier to protect enzymes from the cytosol and a selectively permeable membrane to mediate transport of enzyme substrates and products. The structural and mechanical nature of native carboxysomes remain unclear. Here, we isolate functional β-carboxysomes from the cyanobacterium Synechococcus elongatus PCC7942 and perform the first characterization of the macromolecular architecture and inherent physical mechanics of single β-carboxysomes using electron microscopy, atomic force microscopy (AFM) and proteomics. Our results illustrate that the intact β-carboxysome comprises three structural domains, a single-layered icosahedral shell, an inner layer and paracrystalline arrays of interior Rubisco. We also observe the protein organization of the shell and partial β-carboxysomes that likely serve as the β-carboxysome assembly intermediates. Furthermore, the topography and intrinsic mechanics of functional β-carboxysomes are determined in native conditions using AFM and AFM-based nanoindentation, revealing the flexible organization and soft mechanical properties of β-carboxysomes compared to rigid viruses. Our study provides new insights into the natural characteristics of β-carboxysome organization and nanomechanics, which can be extended to diverse bacterial microcompartments and are important considerations for the design and engineering of functional carboxysomes in other organisms to supercharge photosynthesis. It offers an approach for inspecting the structural and mechanical features of synthetic metabolic organelles and protein scaffolds in bioengineering

High-resolution temporal profiling of transcripts during Arabidopsis leaf senescence reveals a distinct chronology of processes and regulation

Leaf senescence is an essential developmental process that impacts dramatically on crop yields and involves altered regulation of thousands of genes and many metabolic and signaling pathways, resulting in major changes in the leaf. The regulation of senescence is complex, and although senescence regulatory genes have been characterized, there is little information on how these function in the global control of the process. We used microarray analysis to obtain a highresolution time-course profile of gene expression during development of a single leaf over a 3-week period to senescence. A complex experimental design approach and a combination of methods were used to extract high-quality replicated data and to identify differentially expressed genes. The multiple time points enable the use of highly informative clustering to reveal distinct time points at which signaling and metabolic pathways change. Analysis of motif enrichment, as well as comparison of transcription factor (TF) families showing altered expression over the time course, identify clear groups of TFs active at different stages of leaf development and senescence. These data enable connection of metabolic processes, signaling pathways, and specific TF activity, which will underpin the development of network models to elucidate the process of senescence

Moebius strip enterprises and expertise in the creative industries: new challenges for lifelong learning?

The paper argues that the emergence of a new mode of production – co-configuration is generating new modes of expertise that EU policies for lifelong learning are not designed to support professionals to develop. It maintains that this change can be seen most clearly when we analyse Small and Medium Size (SMEs) enterprises in the creative industries. Drawing on concepts from Political Economy - ‘Moebius strip enterprise/expertise’ and Cultural Historical Activity Theory - project-object’ and the ‘space of reasons’, the paper highlights conceptually and through a case study of an SME in the creative industries what is distinctive about the new modes of expertise, before moving on to reconceptualise expertise and learning and to consider the implications of this reconceptualisation for EU policies for lifelong learning. The paper concludes that the new challenge for LLL is to support the development of new forms expertise that are difficult to credentialise, yet, are central to the wider European goal of realising a knowledge economy

Guided graded exercise self-help plus specialist medical care versus specialist medical care alone for chronic fatigue syndrome (GETSET): a pragmatic randomised controlled trial

Background: Graded exercise therapy is an effective and safe treatment for chronic fatigue syndrome, but it is therapist intensive and availability is limited. We aimed to test the efficacy and safety of graded exercise delivered as guided self-help. Methods: In this pragmatic randomised controlled trial, we recruited adult patients (18 years and older) who met the UK National Institute for Health and Care Excellence criteria for chronic fatigue syndrome from two secondary-care clinics in the UK. Patients were randomly assigned to receive specialist medical care (SMC) alone (control group) or SMC with additional guided graded exercise self-help (GES). Block randomisation (randomly varying block sizes) was done at the level of the individual with a computer-generated sequence and was stratified by centre, depression score, and severity of physical disability. Patients and physiotherapists were necessarily unmasked from intervention assignment; the statistician was masked from intervention assignment. SMC was delivered by specialist doctors but was not standardised; GES consisted of a self-help booklet describing a six-step graded exercise programme that would take roughly 12 weeks to complete, and up to four guidance sessions with a physiotherapist over 8 weeks (maximum 90 min in total). Primary outcomes were fatigue (measured by the Chalder Fatigue Questionnaire) and physical function (assessed by the Short Form-36 physical function subscale); both were self-rated by patients at 12 weeks after randomisation and analysed in all randomised patients with outcome data at follow-up (ie, by modified intention to treat). We recorded adverse events, including serious adverse reactions to trial interventions. We used multiple linear regression analysis to compare SMC with GES, adjusting for baseline and stratification factors. This trial is registered at ISRCTN, number ISRCTN22975026. Findings: Between May 15, 2012, and Dec 24, 2014, we recruited 211 eligible patients, of whom 107 were assigned to the GES group and 104 to the control group. At 12 weeks, compared with the control group, mean fatigue score was 19·1 (SD 7·6) in the GES group and 22·9 (6·9) in the control group (adjusted difference −4·2 points, 95% CI −6·1 to −2·3, p<0·0001; effect size 0·53) and mean physical function score was 55·7 (23·3) in the GES group and 50·8 (25·3) in the control group (adjusted difference 6·3 points, 1·8 to 10·8, p=0·006; 0·20). No serious adverse reactions were recorded and other safety measures did not differ between the groups, after allowing for missing data. Interpretation: GES is a safe intervention that might reduce fatigue and, to a lesser extent, physical disability for patients with chronic fatigue syndrome. These findings need confirmation and extension to other health-care settings