Yeast Features: Identifying Significant Features Shared Among Yeast Proteins for Functional Genomics

Background
High throughput yeast functional genomics experiments are revealing associations among tens to hundreds of genes using numerous experimental conditions. To fully understand how the identified genes might be involved in the observed system, it is essential to consider the widest range of biological annotation possible. Biologists often start their search by collating the annotation provided for each protein within databases such as the Saccharomyces Genome Database, manually comparing them for similar features, and empirically assessing their significance. Such tasks can be automated, and more precise calculations of the significance can be determined using established probability measures. 
Results
We developed Yeast Features, an intuitive online tool to help establish the significance of finding a diverse set of shared features among a collection of yeast proteins. A total of 18,786 features from the Saccharomyces Genome Database are considered, including annotation based on the Gene Ontology’s molecular function, biological process and cellular compartment, as well as conserved domains, protein-protein and genetic interactions, complexes, metabolic pathways, phenotypes and publications. The significance of shared features is estimated using a hypergeometric probability, but novel options exist to improve the significance by adding background knowledge of the experimental system. For instance, increased statistical significance is achieved in gene deletion experiments because interactions with essential genes will never be observed. We further demonstrate the utility by suggesting the functional roles of the indirect targets of an aminoglycoside with a known mechanism of action, and also the targets of an herbal extract with a previously unknown mode of action. The identification of shared functional features may also be used to propose novel roles for proteins of unknown function, including a role in protein synthesis for YKL075C.
Conclusions
Yeast Features (YF) is an easy to use web-based application (http://software.dumontierlab.com/yeastfeatures/) which can identify and prioritize features that are shared among a set of yeast proteins. This approach is shown to be valuable in the analysis of complex data sets, in which the extracted associations revealed significant functional relationships among the gene products.
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Therapies with CCL25 require controlled release via microparticles to avoid strong inflammatory reactions

Background: Chemokine therapy with C-C motif chemokine ligand 25 (CCL25) is currently under investigation as a promising approach to treat articular cartilage degeneration. We developed a delayed release mechanism based on Poly (lactic-co-glycolic acid) (PLGA) microparticle encapsulation for intraarticular injections to ensure prolonged release of therapeutic dosages. However, CCL25 plays an important role in immune cell regulation and inflammatory processes like T-cell homing and chronic tissue inflammation. Therefore, the potential of CCL25 to activate immune cells must be assessed more thoroughly before further translation into clinical practice. The aim of this study was to evaluate the reaction of different immune cell subsets upon stimulation with different dosages of CCL25 in comparison to CCL25 released from PLGA particles. Results: Immune cell subsets were treated for up to 5 days with CCL25 and subsequently analyzed regarding their cytokine secretion, surface marker expression, polarization, and migratory behavior. The CCL25 receptor C-C chemokine receptor type 9 (CCR9) was expressed to a different extent on all immune cell subsets. Direct stimulation of peripheral blood mononuclear cells (PBMCs) with high dosages of CCL25 resulted in strong increases in the secretion of monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), interleukin-1 beta (IL-1 beta), tumor-necrosis-factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), upregulation of human leukocyte antigen-DR (HLA-DR) on monocytes and CD4(+) T-cells, as well as immune cell migration along a CCL25 gradient. Immune cell stimulation with the supernatants from CCL25 loaded PLGA microparticles caused moderate increases in MCP-1, IL-8, and IL-1 beta levels, but no changes in surface marker expression or migration. Both CCL25-loaded and unloaded PLGA microparticles induced an increase in IL-8 and MCP-1 release in PBMCs and macrophages, and a slight shift of the surface marker profile towards the direction of M2-macrophage polarization. Conclusions: While supernatants of CCL25 loaded PLGA microparticles did not provoke strong inflammatory reactions, direct stimulation with CCL25 shows the critical potential to induce global inflammatory activation of human leukocytes at certain concentrations. These findings underline the importance of a safe and reliable release system in a therapeutic setup. Failure of the delivery system could result in strong local and systemic inflammatory reactions that could potentially negate the benefits of chemokine therapy

HIV decline in Zimbabwe due to reductions in risky sex? Evidence from a comprehensive epidemiological review.

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HIV decline in Zimbabwe due to reductions in risky sex? Evidence from a comprehensive epidemiological review

Background Recent data from antenatal clinic (ANC) surveillance and general population surveys suggest substantial declines in human immunodeficiency virus (HIV) prevalence in Zimbabwe. We assessed the contributions of rising mortality, falling HIV incidence and sexual behaviour change to the decline in HIV prevalence. Methods Comprehensive review and secondary analysis of national and local sources on trends in HIV prevalence, HIV incidence, mortality and sexual behaviour covering the period 1985-2007. Results HIV prevalence fell in Zimbabwe over the past decade (national estimates: from 29.3% in 1997 to 15.6% in 2007). National census and survey estimates, vital registration data from Harare and Bulawayo, and prospective local population survey data from eastern Zimbabwe showed substantial rises in mortality during the 1990s levelling off after 2000. Direct estimates of HIV incidence in male factory workers and women attending pre- and post-natal clinics, trends in HIV prevalence in 15-24-year-olds, and back-calculation estimates based on the vital registration data from Harare indicated that HIV incidence may have peaked in the early 1990s and fallen during the 1990s. Household survey data showed reductions in numbers reporting casual partners from the late 1990s and high condom use in non-regular partnerships between 1998 and 2007. Conclusions These findings provide the first convincing evidence of an HIV decline accelerated by changes in sexual behaviour in a southern African country. However, in 2007, one in every seven adults in Zimbabwe was still infected with a life-threatening virus and mortality rates remained at crisis leve

Social representations of HIV/AIDS in five Central European and Eastern European countries: A multidimensional analysis

Cognitive processing models of risky sexual behaviour have proliferated in the two decades since the first reporting of HIV/AIDS, but far less attention has been paid to individual and group representations of the epidemic and the relationship between these representations and reported sexual behaviours. In this study, 494 business people and medics from Estonia, Georgia, Hungary, Poland and Russia sorted free associations around HIV/AIDS in a matrix completion task. Exploratory factor and multidimensional scaling analyses revealed two main dimensions (labelled ‘Sex’ and ‘Deadly disease’), with significant cultural and gender variations along both dimension scores. Possible explanations for these results are discussed in the light of growing concerns over the spread of the epidemic in this region

The evolution of HIV policy in Vietnam: from punitive control measures to a more rights-based approach

Aim: Policymaking in Vietnam has traditionally been the preserve of the political elite, not open to the scrutiny of those outside the Communist Party. This paper aims to analyse Vietnam's HIV policy development in order to describe and understand the policy content, policy-making processes, actors and obstacles to policy implementation. Methods: Nine policy documents on HIV were analysed and 17 key informant interviews were conducted in Hanoi and Quang Ninh Province, based on a predesigned interview guide. Framework analysis, a type of qualitative content analysis, was applied for data analysis. Results: Our main finding was that during the last two decades, developments in HIV policy in Vietnam were driven in a top-down way by the state organs, with support and resources coming from international agencies. Four major themes were identified: HIV policy content, the policy-making processes, the actors involved and human resources for policy implementation. Vietnam's HIV policy has evolved from one focused on punitive control measures to a more rights-based approach, encompassing harm reduction and payment of health insurance for medical costs of patients with HIV-related illness. Low salaries and staff reluctance to work with patients, many of whom are drug users and female sex workers, were described as the main barriers to low health staff motivation. Conclusion: Health policy analysis approaches can be applied in a traditional one party state and can demonstrate how similar policy changes take place, as those found in pluralistic societies, but through more top-down and somewhat hidden processes. Enhanced participation of other actors, like civil society in the policy process, is likely to contribute to policy formulation and implementation that meets the diverse needs and concerns of its population

Is there scope for cost savings and efficiency gains in HIV services? A systematic review of the evidence from low- and middle-income countries.

OBJECTIVE: To synthesize the data available--on costs, efficiency and economies of scale and scope--for the six basic programmes of the UNAIDS Strategic Investment Framework, to inform those planning the scale-up of human immunodeficiency virus (HIV) services in low- and middle-income countries. METHODS: The relevant peer-reviewed and "grey" literature from low- and middle-income countries was systematically reviewed. Search and analysis followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. FINDINGS: Of the 82 empirical costing and efficiency studies identified, nine provided data on economies of scale. Scale explained much of the variation in the costs of several HIV services, particularly those of targeted HIV prevention for key populations and HIV testing and treatment. There is some evidence of economies of scope from integrating HIV counselling and testing services with several other services. Cost efficiency may also be improved by reducing input prices, task shifting and improving client adherence. CONCLUSION: HIV programmes need to optimize the scale of service provision to achieve efficiency. Interventions that may enhance the potential for economies of scale include intensifying demand-creation activities, reducing the costs for service users, expanding existing programmes rather than creating new structures, and reducing attrition of existing service users. Models for integrated service delivery--which is, potentially, more efficient than the implementation of stand-alone services--should be investigated further. Further experimental evidence is required to understand how to best achieve efficiency gains in HIV programmes and assess the cost-effectiveness of each service-delivery model

Optical bench development for LISA

For observation of gravitational waves at frequencies between 30 μHz and 1 Hz, the LISA mission will be implemented in a triangular constellation of three identical spacecraft, which are mutually linked by laser interferometry in an active transponder scheme over a 5 million kilometer arm length. On the end point of each laser link, remote and local beam metrology with respect to inertial proof masses inside the spacecraft is realized by the LISA Optical Bench. It implements further- more various ancillary functions such as point-ahead correction, acquisition sensing, transmit beam conditioning, and laser redundancy switching. A comprehensive design of the Optical Bench has been developed, which includes all of the above mentioned functions and at the same time ensures manufacturability on the basis of hydroxide catalysis bonding, an ultrastable integration technology already perfected in the context of LISA's technology demonstrator mission LISA Pathfinder. Essential elements of this design have been validated by dedicated pre-investigations. These include the demonstration of polarizing heterodyne interferometry at the required Picometer and Nanoradian performance levels, the investigation of potential non-reciprocal noise sources in the so-called backlink fiber, as well as the development of a laser redundancy switch breadboard

Information system for image classification based on frequency curve proximity

With the size digital collections are currently reaching, retrieving the best match of a document from large collections by comparing hundreds of tags is a task that involves considerable algorithm complexity, even more so if the number of tags in the collection is not fixed. For these cases, similarity search appears to be the best retrieval method, but there is a lack of techniques suited for these conditions. This work presents a combination of machine learning algorithms put together to find the most similar object of a given one in a set of pre-processed objects based only on their metadata tags. The algorithm represents objects as character frequency curves and is capable of finding relationships between objects without an apparent association. It can also be parallelized using MapReduce strategies to perform the search. This method can be applied to a wide variety of documents with metadata tags. The case-study used in this work to demonstrate the similarity search technique is that of a collection of image objects in JavaScript Object Notation (JSON) containing metadata tags.This work has been done in the context of the project “ASASEC (Advisory System Against Sexual Exploitation of Children)” (HOME/2010/ISEC/AG/043) supported by the European Union with the program “Prevention and fight against crime”.info:eu-repo/semantics/publishedVersio