bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptation in protein fitness landscapes is facilitated by indirect paths
Authors: Wu Nicholas C. , Dai Lei , Olson C. Anders , Lloyd-Smith James O. , Sun Ren 
Published: March 2016

AbstractThe structure of fitness landscapes is critical for understanding adaptive protein evolution (e.g. antimicrobial resistance, affinity maturation, etc.). Due to limited throughput in fitness measurements, previous empirical studies on fitness landscapes were confined to either the neighborhood around the wild type sequence, involving mostly single and double mutants, or a combinatorially complete subgraph involving only two amino acids at each site. In reality, however, the dimensionality of protein sequence space is higher (20L,Lbeing the length of the relevant sequence) and there may be higher-order interactions among more than two sites. To study how these features impact the course of protein evolution, we experimentally characterized the fitness landscape of four sites in the IgG-binding domain of protein G, containing 204= 160,000 variants. We found that the fitness landscape was rugged and direct paths of adaptation were often constrained by pairwise epistasis. However, while direct paths were blocked by reciprocal sign epistasis, we found systematic evidence that such evolutionary traps could be circumvented by “extra-dimensional bypass”. Extra dimensions in sequence space – with a different amino acid at the site of interest or an additional interacting site – open up indirect paths of adaptation via gain and subsequent loss of mutations. These indirect paths alleviate the constraint on reaching high fitness genotypes via selectively accessible trajectories, suggesting that the heretofore neglected dimensions of sequence space may completely change our views on how proteins evolve.
Costs of Clock-Environment Misalignment in Individual Cyanobacterial Cells
Authors: Lambert Guillaume , Chew Justin , Rust Michael J. 
Published: March 2016

AbstractCircadian rhythms are endogenously generated daily oscillations in physiology found in all kingdoms of life. Experimental studies have shown that the fitness ofSynechococcus elongatus, a photosynthetic microorganism, is severely affected in non-24h environments. However, it has been difficult to study the effects of clock-environment mismatch on cellular physiology because such measurements require the precise determination of both clock state and growth rates in the same cell. Here, we designed a microscopy platform that allows us to expose cyanobacterial cells to pulses of light and dark while quantitatively measuring their growth, division rate, and circadian clock state over many days. Our measurements reveal that decreased fitness can result from a catastrophic growth arrest caused by unexpected darkness in a small subset of cells with incorrect clock times corresponding to the subjective morning. We find that the clock generates rhythms in the instantaneous growth rate of the cell, and that time of darkness vulnerability coincides with the time of most rapid growth. Thus, the clock mediates a fundamental trade-off between growth and starvation tolerance in cycling environments. By measuring the response of the circadian rhythm to dark pulses of varying lengths, we constrain a mathematical model of a population’s fitness under arbitrary light/dark schedules. This model predicts that the circadian clock is only advantageous in highly regular cycling environments with frequencies sufficiently close to the natural frequency of the clock.
Phylogenetic expression profiling reveals widespread coordinated evolution of gene expression
Authors: Martin Trevor , Fraser Hunter B. 
Published: March 2016

AbstractPhylogenetic profiling, which infers functional relationships between genes based on patterns of gene presence/absence across species, has proven to be highly effective. Here we introduce a complementary approach, phylogenetic expression profiling (PEP), which detects gene sets with correlated expression levels across a phylogeny. Applying PEP to RNA-seq data consisting of 657 samples from 309 diverse unicellular eukaryotes, we found several hundred gene sets evolving in a coordinated fashion. These allowed us to predict a role of the Golgi apparatus in Alzheimer’s disease, as well as novel genes related to diabetes pathways. We also detected adaptive evolution of tRNA ligase levels to match genome-wide codon usage. In sum, we found that PEP is an effective method for inferring functional relationships—especially among core cellular components that are never lost, to which phylogenetic profiling cannot be applied—and that many subunits of the most conserved molecular machines are coexpressed across eukaryotes.
Tuberous Sclerosis Australia: a case study of a maturing patient-driven organisation
Authors: Stuart Clare Pinkerton 
Published: March 2016

Purpose
– Tuberous Sclerosis Australia (TSA) is a small rare disease organisation with a large scope. TSA was established in 1981 as a peer support organisation. Since then, its role has evolved to meet the needs of its members: individuals living with tuberous sclerosis complex (TSC), their families and health professionals. The paper aims to discuss these issues.

Design/methodology/approach
– This case study describes the diverse activities of TSA which include, but are not limited to: the provision of information and support services; sponsorship of research and fostering a network of TSC health professionals. The benefits of collaborations forged under the umbrella organisation TSC International are highlighted.

Findings
– The case study demonstrates some of the key challenges TSA faces, challenges shared by many similar health charities. These include: funding of health education and promotion activities; working with a large range of health professionals and the challenge of research fatigue.

Originality/value
– There is little research published describing the work of small disease specific organisations similar to TSA. This case study provides insight for those collaborating with similar organisations including health professionals and researchers.
Advances in Tuberous Sclerosis Complex (TSC) research
Authors: Underwood Lisa 
Published: March 2016

Purpose– The purpose of this paper is to provide a brief, descriptive overview of Tuberous Sclerosis Complex (TSC) research with particular reference to studies on Autism Spectrum Disorder (ASD).Design/methodology/approach– A search of electronic databases was carried out to identify English language articles on TSC. The literature was explored in more detail with a focus on neurodevelopmental disorders associated with TSC such as ASD.Findings– The review included 3,679 references. The earliest articles identified were published in the early twentieth century. Since then research on TSC has advanced rapidly and is being carried out worldwide. Just 62 studies have focused on ASD in TSC, although the number of publications is increasing over time.Research limitations/implications– More research on ASD in TSC is needed to benefit those affected by TSC and the broader ASD scientific community.Practical implications– Practitioners working with children and adults with ASD should be aware of the wider health issues experienced by those with genetic conditions such as TSC. Similarly, clinicians working with those who have TSC should be aware of the high prevalence of ASD in the group and implications for the way they work with their patients.Originality/value– This is the first paper to map and characterise the scientific literature on TSC. There remains a focus on the biomedical aspects of TSC with fewer studies on psychosocial/educational or family impacts. The review concludes with recommended research questions for the future.
Towards an improved understanding of TSC-Associated Neuropsychiatric Disorders (TAND)
Authors: Leclezio Loren , de Vries Petrus 
Published: March 2016

Purpose– Tuberous Sclerosis Complex (TSC) is associated with many learning, behavioural, neurodevelopmental and psychiatric difficulties. Over 90 per cent of those with TSC will have some of these concerns, yet typically no more than 20 per cent receive support and treatment. The purpose of this paper is to provide an overview of TSC-Associated Neuropsychiatric Disorders (TAND), explore barriers to identification and management of TAND, and propose possible next steps to improve assessment and treatment of TAND.Design/methodology/approach– The paper combines a brief review of the multiple levels of TAND with a conceptual analysis of barriers and potential facilitators to assessment and intervention for TAND.Findings– Results suggest that the perceived uniqueness of TAND leads to treatment paralysis for most healthcare professionals, thus explaining the assessment and treatment gap seen for TAND. This may in part be due to the multi-dimensionality of TAND, and in part due to lack of access to clear, useful and evidence-based resources for TAND.Research limitations/implications– Identification of natural TAND clusters through machine-based learning and data reduction methodologies may yield a manageable number of natural groups of TSC-related neuropsychiatric problems, for which a basic “toolkit” of evidence-based interventions could be developed.Practical implications– Families and clinicians will benefit from a toolkit of tried and tested resources and evidence-based information to guide further investigation and management of TAND.Originality/value– Even though individuals will have unique TAND profiles, there may be key natural TAND clusters – combinations of behaviours across multi-dimensional levels – that will simplify and improve access to further evaluation, treatment and neuroscientific research.
The Internet of Things in manufacturing innovation processes
Authors: Caputo Andrea , Marzi Giacomo , Pellegrini Massimiliano Matteo 
Published: March 2016

Purpose
– The purpose of this paper is to contribute and enrich the scientific debate about the phenomenon called the Internet of Things (IoT) from a managerial perspective. Through the lenses of management and innovation literature, the authors investigate the main facts that characterize the IoT and developed a conceptual framework to interpret its evolution. The framework has then been applied to the case of a three-dimensional (3D) printing technology used for additive manufacturing.

Design/methodology/approach
– A theoretical analysis of the phenomenon of the IoT and its main elements has been performed to construct a conceptual framework in a managerial fashion able to describe the evolutionary impacts of the phenomenon on the manufacturing industry.

Findings
– Through consequential steps, namely radical, modular, architectural and incremental innovation, and by adopting and integrating the Henderson and Clark model, the authors explain the cornerstones of the evolutionary impact of the IoT on the manufacturing industry. Finally, the authors apply the framework to the case of additive manufacturing and 3D printing.

Practical implications
– The framework’s practical value is related to its employability in interpreting and possibly forecasting the evolution of manufacturing industries thanks to the advent of the IoT, allowing managers to capture value arising from technological changes.

Originality/value
– This study offers a clear and simple model to interpret the impacts of the IoT. Such a goal has been obtained by systematizing the disconnected research on the topic and arranging such contributions into solid paradigms of the managerial literature.
Internet of Things
Authors: Scuotto Veronica , Ferraris Alberto , Bresciani Stefano 
Published: March 2016

Purpose
– An empirical testing on IBM smart cities projects was applied so as to demonstrate that the combination between the use of Internet of Things (IoT) and the implementation of the Open Innovation (OI) model within smart cities which has been changed the development of urban areas and effected firms’ innovativeness. The paper aims to discuss these issues.

Design/methodology/approach
– A case study methodology on a leading multinational firms deeply involved in smart cities projects has been chosen.

Findings
– From this study it emerged how IBM: has a clear vision of smart cities and IoT; adopt a worldwide OI approach to smart cities; delineate-specific strategies and create OI units ad hoc for smart cities’ projects.

Research limitations/implications
– The major limitation of this work is that the analysis presented has been developed only on one case of multinational firm that operate in smart cities contexts.

Practical implications
– Recommendations will be made both to public and private actor in order to plan and implement efficient strategies to improve their performances.

Originality/value
– The concept of smart city has become quite popular between scholars and practitioners in the era of digital economy. Cities become smart developing new urban area using new Information and Communication Technologies such as mobile devices, the semantic web, cloud computing, and the IoT. Smart cities make innovation ecosystem, joining together different forces like knowledge-intensive activities, institutions for cooperation and learning, and web-based applications collective intelligence. This research is of importance and significance to scholars, government, and firms who need to understand the relevance of smart cities in the current economy.
Evaluating the innovation of the Internet of Things
Authors: Murray Alan , Papa Armando , Cuozzo Benedetta , Russo Giuseppe 
Published: March 2016

Purpose– The Internet of Things (IoT) represents the network connection of people, processes, data and things. Due to the relevant position that this intelligent infrastructure is acquiring, the purpose of this paper is to investigate the effects of IoT on the companies’ value, with specific reference to the intellectual capital value.Design/methodology/approach– The methodology is based on a single case study approach with an empirical analysis which aims to analyse whether and how the introduction of the IoT’ innovations influences the value of the intellectual capital owned by a company. The evaluation method used for the empirical analysis is the Economic Value Added. The application is carried out on the company “Cisco Systems Inc.” by analysing the company’s financial reports covering the period 2007-2014.Findings– The paper demonstrates the impact of the innovation of IoT on intellectual capital owned by a high intensity cognitive company by determining its economic value. The results demonstrate that the introduction of projects involving the use of the IoT has increased the value of intellectual capital over the years.Originality/value– As the IoT can guarantee efficiency, social and individual benefits, the effects of the IoT on company performance and, particularly, on intangible corporate dimensions are analysed. Hence, the paper is directed to fill the literature gap on the analysis and evaluation of the IoT’ impact on intellectual capital owned by high intensity cognitive companies. The research proposes strategic advice for decision making of companies interested in new technology investments.
Business process support for IoT based product-service systems (PSS)
Authors: Zancul Eduardo de Senzi , Takey Silvia M. , Barquet Ana Paula Bezerra , Kuwabara Leonardo Heiji , Cauchick Miguel Paulo A. , Rozenfeld Henrique 
Published: March 2016

Purpose
– The purpose of this paper is to propose a method for adopting an Internet of Things (IoT) enabled product-service system (PSS) considering business model and product enhancements. The method focusses on business process implications of IoT. The paper also discusses a real application of the proposed method to the machinery industry.

Design/methodology/approach
– Considering the IoT technologies available, failure mode and effects analysis is applied to identify what should be monitored in the product to minimize potential product failures. In parallel, in order to assist the company in deciding which PSS strategy to be followed, a Configurator of PSS proposals is applied. The results are derived to define the IoT architecture and the business process design supported by the selected IoT technologies.

Findings
– The main findings include the proposed IoT-enabled PSS adoption method, illustrated by the description of the application and its assessment. In addition, the identification of key process areas that are impacted by IoT is offered, namely: remote machine setup; corrective and predictive maintenance; material supply; product pricing; and information reporting.

Research limitations/implications
– The application of the method proposed is limited to one company. Future work includes extending the application of the method to other units of analysis.

Practical implications
– The method proposed can be considered by companies willing to increase product-service revenues based on IoT technologies.

Originality/value
– The IoT-enabled PSS adoption method is an approach grounded on the intersection theories of PSSs and the more technology-oriented IoT developments.
Internet of Things and business processes redesign in seaports: The case of Hamburg
Authors: Ferretti Marco , Schiavone Francesco 
Published: March 2016

Purpose
– The purpose of this paper is to contribute to the extant literature about the exploitation of Internet of Things (IoT) in seaports by illustrating in detail how such IT infrastructures can impact on the redesign of their business processes. Thus, the research question of the study is: how do IoT technologies redesign the business processes of seaports?

Design/methodology/approach
– The paper reports the illustrative case study of the German Port of Hamburg, one of the main European seaports, which widely adopted technologies based on IoT over the last few years.

Findings
– The results show the adoption of IoT technologies widely redesigns and improves the performance of all the main business process of the port analyzed, in particular those processes related to technology and information of the organization. The IoT-driven business process redesign (BPR) must be planned strategically by the port management and implies the involvement of all the port stakeholders and, if necessary, the hiring external professional partners.

Originality/value
– Despite some authors report generically which are the ports operational domains more affected by IoT, there is a lack of studies about the specific implications of the adoption of such technologies on the BPR of seaports. The paper fills in this gap.
Discovering the Internet of Things (IoT) within the business process management
Authors: Del Giudice Manlio 
Published: March 2016

Purpose
– We still know very little about how the Internet of Things (IoT) is changing the way of interpreting the business process management inside and outside firms and this topic is progressively becoming increasingly hot in the leading managerial literature (Al-Mashari and Zairi, 2000). Furthermore, management scholars are aiming at investigating the impact and the role of the IoT on the business process management in terms of promotion of knowledge flow, innovation and competitiveness. Likewise, management researchers aim at understanding how the IoT fosters innovation within organizations and which implications this phenomenon may have on the business process management and competitiveness of firms (Al-Mashari and Zairi, 1999). The purpose of this paper is to offer a literature review on the topic, by considering the technological revitalization through the IoT as a key driver for the business process management of the industrial firm.

Design/methodology/approach
– The present paper offers a literature review of the most relevant contributions on IoT and business process management. It presents a qualitative approach to the discussion of the technological revitalization concept within industrial firms using IoT technologies.

Findings
– The rising number of technical contributions using IoT shows that technologies are evolving and there is a learning and application process supported by standardization efforts. Easy installation, standardization, stoutness, configuration and servicing are essential to keep IoT systems operational and hence offering value for the business process management within every industry. From a business process management point of view, value creation from the IoT application to technological revitalizations is pivotal and will affect the use of IoT technologies in the industry, on a progressively higher scale, in the coming years.

Originality/value
– There are still few contributions in the managerial literature that show the implications of the IoT on business process management of industrial firms and, particularly, on technological revitalization. The paper offers a literature review on the topic, at the same presenting some reflections on the application of the IoT to technological revitalizations, within industrial contexts.
Understanding employee turnover in humanitarian organizations
Authors: Dubey Rameshwar , Gunasekaran Angappa , Altay Nezih , Childe Stephen J , Papadopoulos Thanos 
Published: March 2016

Purpose– At a time when the number and seriousness of disasters seems to be increasing, humanitarian organizations find that besides their challenging work they are faced with problems caused by a high level of turnover of staff. The paper aims to discuss these issues.Design/methodology/approach– Based on the 24 variables leading to employee turnover identified by Cotton and Tuttle (1986) the authors analyse the work-related, external and personal factors affecting employee turnover in humanitarian organizations, using a survey of members of the Indian National Institute of Disaster Management.Findings– Results indicated that the three factors are present. Of the external factors, only employment perception had a factor loading over 0.7; of the work-related factors, all were significant; of the personal factors, biographical information, marital status, number of dependants, aptitude and ability and intelligence had the highest loadings. It was also shown that behavioural intentions and net expectation were not significant.Originality/value– Only a few studies reported on employee turnover and its reasons are not well understood in the context of humanitarian organizations. To address this need, the aim of this paper is to explore the personal reasons impacting employee turnover in humanitarian organizations. In the study the authors have adopted 24 variables used in Cotton and Tuttle (1986) and classified into constructs to explain turnover, and further tested the model using data gathered from humanitarian organizations.