Learning to extract relations for protein annotation

MOTIVATION: Protein annotation is a task that describes protein X in terms of topic Y. Usually, this is constructed using information from the biomedical literature. Until now, most of literature-based protein annotation work has been done manually by human annotators. However, as the number of biomedical papers grows ever more rapidly, manual annotation becomes more difficult, and there is increasing need to automate the process. Recently, information extraction (IE) has been used to address this problem. Typically, IE requires pre-defined relations and hand-crafted IE rules or annotated corpora, and these requirements are difficult to satisfy in real-world scenarios such as in the biomedical domain. In this article, we describe an IE system that requires only sentences labelled according to their relevance or not to a given topic by domain experts. RESULTS: We applied our system to meet the annotation needs of a well-known protein family database; the results show that our IE system can annotate proteins with a set of extracted relations by learning relations and IE rules for disease, function and structure from only relevant and irrelevant sentences.     

Process control in cell culture technology using dielectric spectroscopy

In the biopharmaceutical industry, mammalian and insect cells as well as plant cell cultures are gaining worldwide importance to produce biopharmaceuticals and as products themselves, for example in stem cell therapy. These highly sophisticated cell-based production processes need to be monitored and controlled to guarantee product quality and to satisfy GMP requirements. With the process analytical technology (PAT) initiative, requirements regarding process monitoring and control have changed and real-time in-line monitoring tools are now recommended. Dielectric spectroscopy (DS) can serve as a tool to satisfy some PAT requirements. DS has been used in the medical field for quite some time and it may allow real-time process monitoring of biological cell culture parameters. DS has the potential to enable process optimization, automation, cost reduction, and a more consistent product quality. Dielectric spectroscopy is reviewed here as a tool to monitor biochemical processes. Commercially available dielectric sensing systems are discussed. The potential of this technology is demonstrated through examples of current and potential future applications in research and industry for mammalian and insect cell culture.     

Efficiently mining gene expression data via a novel parameterless clustering method

Clustering analysis has been an important research topic in the machine learning field due to the wide applications. In recent years, it has even become a valuable and useful tool for in-silico analysis of microarray or gene expression data. Although a number of clustering methods have been proposed, they are confronted with difficulties in meeting the requirements of automation, high quality, and high efficiency at the same time. In this paper, we propose a novel, parameterless and efficient clustering algorithm, namely, correlation search technique (CST), which fits for analysis of gene expression data. The unique feature of CST is it incorporates the validation techniques into the clustering process so that high quality clustering results can be produced on the fly. Through experimental evaluation, CST is shown to outperform other clustering methods greatly in terms of clustering quality, efficiency, and automation on both of synthetic and real data sets.     

Hybridization and the evolution of invasiveness in plants and other organisms

Less than a decade ago, we proposed that hybridization could serve as a stimulus for the evolution of invasiveness in plants (Ellstrand and Schierenbeck Proc Nat Acad Sci USA 97:7043–7050, 2000). A substantial amount of research has taken place on that topic since the publication of that paper, stimulating the symposium that makes up this special issue. Here we present an update of this emergent field, based both on the papers in this volume and on the relevant literature. We reevaluate the lists that we presented in our earlier paper of reports in which hybridization has preceded the evolution of invasiveness. We discard a few cases that were found to be in error, published only as abstracts, or based on personal communication. Then we augment the list from examples in this volume and a supplementary literature search. Despite the omissions, the total number of cases has increased. Many have been strengthened. We add a list of cases in which there has been evidence that intra-taxon hybridization has preceded the evolution of invasiveness. We also provide a number of examples from organisms other than plants. We consider how our examples suggest mechanisms whereby hybridization may act to stimulate the evolution of invasiveness. Hybridization does not represent the only evolutionary pathway to invasiveness, but it is one that can explain why the appearance of invasiveness often involves a long lag time and/or multiple introductions of exotics.     

Industrial Symbiosis Dynamics and the Problem of Equivalence: Proposal for a Comparative Framework

Industrial symbiosis (IS), one of the founding notions within the field of industrial ecology, has diffused throughout significant parts of the world as a practice that can reduce the ecological impact of the industrial processes of groups of firms. In this article, we propose a fresh look at this research topic, building on the considerable advances that have been made in the last 15 years in understanding how IS comes about. We propose a conceptual and theoretical framework for taking on the challenge of comparative analysis at a global level. This requires developing an approach to address a solution to the problem of equivalence: the difficulty of comparing instances of IS across different institutional contexts. The proposed framework emphasizes IS as a process and attempts to address the obstacles to comparative study by (1) identifying terminology to examine IS variants, (2) providing a typology of IS dynamics, and (3) formulating key research questions to illuminate a way forward. In developing our argument, we build on the collective experiences of collaborative research efforts in North America, Europe, and Asia as evidenced in recent overviews of the literature.     

Mining the pharmacogenomics literature--a survey of the state of the art

This article surveys efforts on text mining of the pharmacogenomics literature, mainly from the period 2008 to 2011. Pharmacogenomics (or pharmacogenetics) is the field that studies how human genetic variation impacts drug response. Therefore, publications span the intersection of research in genotypes, phenotypes and pharmacology, a topic that has increasingly become a focus of active research in recent years. This survey covers efforts dealing with the automatic recognition of relevant named entities (e.g. genes, gene variants and proteins, diseases and other pathological phenomena, drugs and other chemicals relevant for medical treatment), as well as various forms of relations between them. A wide range of text genres is considered, such as scientific publications (abstracts, as well as full texts), patent texts and clinical narratives. We also discuss infrastructure and resources needed for advanced text analytics, e.g. document corpora annotated with corresponding semantic metadata (gold standards and training data), biomedical terminologies and ontologies providing domain-specific background knowledge at different levels of formality and specificity, software architectures for building complex and scalable text analytics pipelines and Web services grounded to them, as well as comprehensive ways to disseminate and interact with the typically huge amounts of semiformal knowledge structures extracted by text mining tools. Finally, we consider some of the novel applications that have already been developed in the field of pharmacogenomic text mining and point out perspectives for future research.     

Exploring the evolution of environmental sex determination, especially in reptiles

Environmental sex determination has been documented in a variety of organisms for many decades and the adaptive significance of this unusual sex-determining mechanism has been clarified empirically in most cases. In contrast, temperature-dependent sex determination (TSD) in amniote vertebrates, first noted 40 years ago in a lizard, has defied a general satisfactory evolutionary explanation despite considerable research effort. After briefly reviewing relevant theory and prior empirical work, we draw attention to recent comparative analyses that illuminate the evolutionary history of TSD in amniote vertebrates and point to clear avenues for future research on this challenging topic. To that end, we then highlight the latest empirical findings in lizards and turtles, as well as promising experimental results from a model organism, that portend an exciting future of progress in finally elucidating the evolutionary cause(s) and significance of TSD.     

On the adaptive value of cytoplasmic genomes in plants

Is DNA variation maintained in organelle genomes selectively neutral? The answer to this question has important implications for many aspects of ecology and evolution. While traditionally the answer has been ‘yes’, recent studies in animals have shown that, on the contrary, mitochondrial DNA polymorphism is frequently adaptive. In plants, however, the neutrality assumption has not been strongly challenged. Here, we begin with a critical evaluation of arguments in favour of this long‐held view. We then discuss the latest empirical evidence for the opposing prediction that sequence variation in plant cytoplasmic genomes is frequently adaptive. While outstanding research progress is being made towards understanding this fundamental topic, we highlight the need for studies that combine information ranging from field experiments to physiology to molecular evolutionary biology. Such an interdisciplinary approach provides a means for determining the frequency, drivers and evolutionary significance of adaptive organelle DNA variation.     

Phenotypic Plasticity in Embryonic Development of Reptiles:Recent Research and Research Opportunities in China

Adaptive developmental plasticity can enable an organism to modify its phenotype rapidly, in response to local(and perhaps, unpredictable) conditions, by altering reaction norms during development. Previous studies on this topic have been dominated by western scientists, employing western study systems and approaches. Recently, the expansion of Chinese ecological research has seen a broadening of studies taxonomically(phylogenetically). Here, we briefly summarize research that has been conducted on developmental plasticity in Chinese reptiles over the past two decades, and suggest productive directions for future studies in this field. There are exciting research opportunities in this field in China, and we call for increased collaboration between western and eastern scientists to elucidate the role of developmental plasticity in evolutionary responses of organisms to environmental changes. As human activities increase the intensity and frequency of such changes, the need to understand responses of biological systems becomes an increasingly urgent priority.     

Applications and trends in systems biology in biochemistry

Systems biology has received an ever increasing interest during the last decade. A large amount of third-party funding is spent on this topic, which involves quantitative experimentation integrated with computational modeling. Industrial companies are also starting to use this approach more and more often, especially in pharmaceutical research and biotechnology. This leads to the question of whether such interest is wisely invested and whether there are success stories to be told for basic science and/or technology/biomedicine. In this review, we focus on the application of systems biology approaches that have been employed to shed light on both biochemical functions and previously unknown mechanisms. We point out which computational and experimental methods are employed most frequently and which trends in systems biology research can be observed. Finally, we discuss some problems that we have encountered in publications in the field.     

Sperm-mediated transgenesis

The idea of using a sperm cell for introducing exogenous DNA into an oocyte at the time of fertilization would be brilliant if only we were sure that it can be done. Since 1989, contradictory reports have appeared in the literature and, at present, no consensus has been reached on the topic. Given the potential impact of this method for the generation of transgenic animals, for both mammalian and non-mammalian species, this review summarizes what has been achieved in this field. While some aspects, such as the binding of DNA molecules to spermatozoa, have now a solid experimental base, others, such as the generation of real transgenic individuals, are still based on disputed evidence. A critical analysis of the most relevant data will be presented in order to provide the tools for an objective evaluation of the efficiency of this method.     

Continuous integrated manufacturing for biopharmaceuticals: A new paradigm or an empty promise?

Continuous integrated bioprocessing has elicited considerable interest from the biopharma industry for the many purported benefits it promises. Today many major biopharma manufacturers around the world are engaged in the development of continuous process platforms for their products. In spite of great potential, the path toward continuous integrated bioprocessing remains unclear for the biologics industry due to legacy infrastructure, process integration challenges, vague regulatory guidelines, and a diverging focus toward novel therapies. In this article, we present a review and perspective on this topic. We explore the status of the implementation of continuous integrated bioprocessing among biopharmaceutical manufacturers. We also present some of the key hurdles that manufacturers are likely to face during this implementation. Finally, we hypothesize that the real impact of continuous manufacturing is likely to come when the cost of manufacturing is a substantial portion of the cost of product development, such as in the case of biosimilar manufacturing and emerging economies.     

Mouse monoclonal antibodies in biological research: strategies for high-throughput production

Mouse monoclonal antibodies have become key components in basic research as well as in the clinical laboratory. Being invaluable tools in many biological assays, they continue to be the primary choice in the research field, although the conventional technology used for hybridoma generation and screening is a still lengthy, time-consuming and low-throughput process. With the advent of genetic immunisation and the application of automation and microarray to the traditional biological assays, the monoclonal antibody field has been revolutionised. Here, we will briefly review the most relevant strategies which have made the manufacture of murine monoclonal antibodies a faster and high-throughput technology.     

The conservation and tourism development of World Natural Heritage sites: The current situation and future prospects of research

The conservation and tourism development of World Heritage (WH) sites has always been a key and urgent scientific issue to be solved urgently by academia and industry all over the world. An increasing number of researchers and practitioners are paying attention to this issue. However, there is a lack of a comprehensive literature review on this topic. To fill this gap, this study conducts a systematic literature review (SLR) based on 179 related studies retrieved from the Web of Science (WoS) and Google Scholar (GS) databases. Focusing on the research question of the conservation and tourism development of World Natural Heritage (WNH) sites, we built an SLR framework to implement the review process. First, quantitative research was conducted to analyse the annual numbers, content and continents of the published literature. Second, we classified and summarized the main progress and achievements from theoretical research, technical methods, model construction, monitoring and evaluating, and application demonstration. Finally, in view of the current research situation of the conservation and tourism development of WNH sites, we proposed eight key scientific issues to be solved and several directions for future research.     

A Multispecies Approach to Co-Sleeping

Human sleeping arrangements have evolved over time and differ across cultures. The majority of adults share their bed at one time or another with a partner or child, and many also sleep with pets. In fact, around half of dog and cat owners report sharing a bed or bedroom with their pet(s). However, interspecies co-sleeping has been trivialized in the literature relative to interpersonal or human-human co-sleeping, receiving little attention from an interdisciplinary psychological perspective. In this paper, we provide a historical outline of the “civilizing process” that has led to current sociocultural conceptions of sleep as an individual, private function crucial for the functioning of society and the health of individuals. We identify similar historical processes at work in the formation of contemporary constructions of socially normative sleeping arrangements for humans and animals. Importantly, since previous examinations of co-sleeping practices have anthropocentrically framed this topic, the result is an incomplete understanding of co-sleeping practices. By using dogs as an exemplar of human-animal co-sleeping, and comparing human-canine sleeping with adult-child co-sleeping, we determine that both forms of co-sleeping share common factors for establishment and maintenance, and often result in similar benefits and drawbacks. We propose that human-animal and adult-child co-sleeping should be approached as legitimate and socially relevant forms of co-sleeping, and we recommend that co-sleeping be approached broadly as a social practice involving relations with humans and other animals. Because our proposition is speculative and derived from canine-centric data, we recommend ongoing theoretical refinement grounded in empirical research addressing co-sleeping between humans and multiple animal species.     

In Pursuit of Closed‐Loop Supply Chains for Critical Materials: An Exploratory Study in the Green Energy Sector

A closed‐loop supply chain (CLSC) is considered not only an important solution for ensuring sustainable exploitation of materials, but also a promising strategy for securing long‐term availability of materials. The latter is especially highlighted in the materials criticality discourse. Critical raw materials (CRMs), being exposed to supply disruptions, create an uncertain operational environment for many industries, particularly for green energy technologies that employ multiple CRMs. However, recycling rates of CRMs are very low and engagement of companies in CLSC for CRM is limited. This study examines factors influencing CLSC for CRM development in photovoltaic panels and wind turbine technologies. The aim is to analyze how the factors manifest themselves in different companies along the supply chain and to identify enabling and bottleneck conditions for implementation of CLSC for CRM. The novelty of the study is twofold: the focus on material rather than product flows, and examination of factors from a multiactor perspective. The evidence obtained suggests that the manufacturing companies and reverse supply‐chain operators engaged in the study take different perspectives (product vs. material) regarding development of CLSC for CRM and thus emphasize different factors. The findings underline the need for interactions between supply‐chain actors, a sound competitive environment for recycling processes, and investment in technologies and infrastructure development if CLSC for CRM is to be developed. The paper provides implications for practitioners and policy makers for implementation of CLSC for CRM, and suggests prospects for further research.     

Bridging the gap

Therapeutic monoclonal antibodies (mAbs) currently dominate the biologics marketplace. Development of a new therapeutic mAb candidate is a complex, multistep process and early stages of development typically begin in an academic research environment. Recently, a number of facilities and initiatives have been launched to aid researchers along this difficult path and facilitate progression of the next mAb blockbuster. Complementing this, there has been a renewed interest from the pharmaceutical industry to reconnect with academia in order to boost dwindling pipelines and encourage innovation. In this review, we examine the steps required to take a therapeutic mAb from discovery through early stage preclinical development and toward becoming a feasible clinical candidate. Discussion of the technologies used for mAb discovery, production in mammalian cells and innovations in single-use bioprocessing is included. We also examine regulatory requirements for product quality and characterization that should be considered at the earliest stages of mAb development. We provide details on the facilities available to help researchers and small-biotech build value into early stage product development, and include examples from within our own facility of how technologies are utilized and an analysis of our client base.     

Surfing the wave of oxyfunctionalization chemistry by engineering fungal unspecific peroxygenases

The selective insertion of oxygen into non-activated organic molecules has to date been considered of utmost importance to synthesize existing and next generation industrial chemicals or pharmaceuticals. In this respect, the minimal requirements and high activity of fungal unspecific peroxygenases (UPOs) situate them as the jewel in the crown of C–H oxyfunctionalization biocatalysts. Although their limited availability and development has hindered their incorporation into industry, the conjunction of directed evolution and computational design is approaching UPOs to practical applications. In this review, we will address the most recent advances in UPO engineering, both of the long and short UPO families, while discussing the future prospects in this fast-moving field of research.     

Guidelines for the use and interpretation of assays for monitoring autophagy

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.