bluuebunny/crossref_metadata_2025_split huggingface dataset:
ModuleDiscoverer: Identification of regulatory modules in protein-protein interaction networks
Authors: Vlaic Sebastian , Tokarski-Schnelle Christian , Gustafsson Mika , Dahmen Uta , Guthke Reinhard , Schuster Stefan 
Published: March 2017

AbstractThe identification of disease associated modules based on protein-protein interaction networks (PPINs) and gene expression data has provided new insights into the mechanistic nature of diverse diseases. A major problem hampering their identification is the detection of protein communities within large-scale, whole-genome PPINs. Current strategies solve the maximal clique enumeration (MCE) problem, i.e., the enumeration of all non-extendable groups of proteins, where each pair of proteins is connected by an edge. The MCE problem however is non-deterministic polynomial time hard and can thus be computationally overwhelming for large-scale, whole-genome PPINs.We present ModuleDiscoverer, a novel approach for the identification of regulatory modules from PPINs in conjunction with gene-expression data. ModuleDiscoverer is a heuristic that approximates the community structure underlying PPINs. Based on a high-confidence PPIN ofRattus norvegicusand publicly available gene expression data we apply our algorithm to identify the regulatory module of a rat-model of diet induced non-alcoholic steatohepatitis (NASH). We validate the module using single-nucleotide polymorphism data from independent genome-wide association studies. Structural analysis of the module reveals 10 sub-modules. These sub-modules are associated with distinct biological functions and pathways that are relevant to the pathological and clinical situation in NASH.ModuleDiscoverer is freely available upon request from the corresponding author.
Conserved roles of RECQ-like helicases Sgs1 and BLM in preventing R-loop associated genome instability
Authors: Novoa Carolina A. , Chang Emily Yun-Chia , Aristizabal Maria J. , Coulombe Yan , Segovia Romulo , Shen Yaoqing , Keong Christelle , Jones Steven J.M. , Masson Jean-Yves , Kobor Michael S. , Stirling Peter C. 
Published: March 2017

AbstractSgs1 is a yeast DNA helicase functioning in DNA replication and repair, and is the orthologue of the human Bloom’s syndrome helicase BLM. Here we analyze the mutation signature associated withSGS1deletion in yeast, and find frequent copy number changes flanked by regions of repetitive sequence and high R-loop forming potential. We show that loss ofSGS1increases R-loop accumulation and sensitizes cells to replication-transcription collisions. Accordingly, insgs1Δ cells the genome-wide distribution of R-loops shifts to known sites of Sgs1 action, replication pausing regions, and to long genes. Depletion of the orthologous BLM helicase from human cancer cells also increases R-loop levels, and R-loop-associated genome instability. In support of a direct effect, BLM is found physically proximal to DNA:RNA hybrids in human cells, and can efficiently unwind R-loopsin vitro. Together our data describe a conserved role for Sgs1/BLM in R-loop suppression and support an increasingly broad view of DNA repair and replication fork stabilizing proteins as modulators of R-loop mediated genome instability.
Identification and characterization of domesticated bacterial transposases
Authors: Bertels Frederic , Gallie Jenna , Rainey Paul B 
Published: March 2017

ABSTRACTSelfish genetic elements (SGEs), such as insertion sequences (ISs) and transposons are found in most genomes. Transposons are usually identifiable by their high copy number within genomes. In contrast REP associated tyrosine transposases (RAYTs), a recently described class of bacterial transposase, are typically present at just one copypergenome. This suggests that RAYTs no longer copy themselves and thus they no longer function as a typical transposase. Motivated by this possibility we interrogated thousands of fully sequenced bacterial genomes in order to determine patterns of RAYT diversity, their distribution across chromosomes and accessory elements, and rate of duplication. RAYTs encompass exceptional diversity and are divisible into at least five distinct groups. They possess features more similar to housekeeping genes than insertion sequences, are predominantly vertically transmitted and have persisted through evolutionary time to the point where they are now found in 24% of all species for which at least one fully sequenced genome is available. Overall, the genomic distribution of RAYTs suggests that they have been co-opted by host genomes to perform a function that benefits the host cell.
Yeastde novogenes preferentially emerge from divergently transcribed, GC-rich intergenic regions
Authors: Vakirlis N Nikolaos , Hebert Alex S , Opulente Dana A , Achaz Guillaume , Hittinger Chris Todd , Fischer Gilles , Coon Josh J , Lafontaine Ingrid 
Published: March 2017

AbstractNew genes, with novel protein functions, can evolve “from scratch” out of intergenic sequences. Thesede novogenes can integrate the cell’s genetic network and drive important phenotypic innovations. Therefore, identifyingde novogenes and understanding how the transition from noncoding to coding occurs are key problems in evolutionary biology. However, identifyingde novogenes is a difficult task, hampered by the presence of remote homologs, fast evolving sequences and erroneously annotated protein coding genes. To overcome these limitations, we developed a procedure that handles the usual pitfalls inde novogene identification and predicted the emergence of 703de novogenes in 15 yeast species from two genera whose phylogeny spans at least 100 million years of evolution. We established thatde novogene origination is a widespread phenomenon in yeasts, only a few being ultimately maintained by selection. We validated 82 candidates, by providing new translation evidence for 25 of them through mass spectrometry experiments. We also unambiguously identified the mutations that enabled the transition from non-coding to coding for 30Saccharomyces de novogenes. We found thatde novogenes preferentially emerge next to divergent promoters in GC-rich intergenic regions where the probability of finding a fortuitous and transcribed ORF is the highest. We found a more than 3-fold enrichment ofde novogenes at recombination hot spots, which are GC-rich and nucleosome-free regions, suggesting that meiotic recombination would be a major driving force ofde novogene emergence in yeasts.
Assessing the reliability of spike-in normalization for analyses of single-cell RNA sequencing data
Authors: Lun Aaron T. L. , Calero-Nieto Fernando J. , Haim-Vilmovsky Liora , Göttgens Berthold , Marioni John C. 
Published: March 2017

AbstractBy profiling the transcriptomes of individual cells, single-cell RNA sequencing provides unparalleled resolution to study cellular heterogeneity. However, this comes at the cost of high technical noise, including cell-specific biases in capture efficiency and library generation. One strategy for removing these biases is to add a constant amount of spike-in RNA to each cell, and to scale the observed expression values so that the coverage of spike-in RNA is constant across cells. This approach has previously been criticized as its accuracy depends on the precise addition of spike-in RNA to each sample, and on similarities in behaviour (e.g., capture efficiency) between the spike-in and endogenous transcripts. Here, we perform mixture experiments using two different sets of spike-in RNA to quantify the variance in the amount of spike-in RNA added to each well in a plate-based protocol. We also obtain an upper bound on the variance due to differences in behaviour between the two spike-in sets. We demonstrate that both factors are small contributors to the total technical variance and have only minor effects on downstream analyses such as detection of highly variable genes and clustering. Our results suggest that spike-in normalization is reliable enough for routine use in single-cell RNA sequencing data analyses.
Pathogenic amino acids in mitochondrial proteins more frequently arise in lineages closely related to human than in distant lineages
Authors: Klink Galya V. , Golovin Andrey V. , Bazykin Georgii A. 
Published: March 2017

AbstractPropensities for different amino acids within a protein site change in the course of evolution, so that an amino acid deleterious in a particular species may be acceptable at the same site in a different species. Here, we study the amino acid-changing variants in human mitochondrial genes, and analyze their occurrence in non-human species. We show that substitutions giving rise to the human amino acid variant tend to occur in lineages closely related to human more frequently than in more distantly related lineages, indicating that a human variant is more likely to be deleterious in more distant species. Unexpectedly, amino acids corresponding to pathogenic alleles in humans also more frequently originate at more closely related lineages. Therefore, a pathogenic variant still tends to be more acceptable in human mitochondria than a variant that may only be fit after a substantial perturbation of the protein structure.SignificanceHomologous proteins can carry different amino acids at the same position in different species. These changes can be neutral, or can reflect differences in the pressure of selection on these sites. We hypothesized that amino acids observable in human population appear on average more frequently in close than in distant human relatives. For mitochondrial proteins, we observe this for both frequent and rare human alleles. Unexpectedly, substitutions that would be pathogenic in humans also more frequently appear in species more closely related to humans than in distantly related ones. Therefore, despite their pathogenicity, these variants are on average more acceptable in humans than other amino acids that were observed at this site in distantly related species.
NovelPlasmodium falciparummetabolic network reconstruction identifies shifts associated with clinical antimalarial resistance
Authors: Carey Maureen A. , Papin Jason A. , Guler Jennifer L. 
Published: March 2017

ABSTRACTBACKGROUNDMalaria remains a major public health burden and resistance has emerged to every antimalarial on the market, including the frontline drug artemisinin. Our limited understanding ofPlasmodiumbiology hinders the elucidation of resistance mechanisms. In this regard, systems biology approaches can facilitate the integration of existing experimental knowledge and further understanding of these mechanisms.RESULTSHere, we developed a novel genome-scale metabolic network reconstruction, iPfal17, of the asexual blood-stageP. falciparumparasite to expand our understanding of metabolic changes that support resistance. We identified 11 metabolic tasks to evaluate iPfal17 performance. Flux balance analysis and simulation of gene knockouts and enzyme inhibition predict candidate drug targets unique to resistant parasites. Moreover, integration of clinical parasite transcriptomes into the iPfal17 reconstruction reveals patterns associated with antimalarial resistance. These results predict that artemisinin sensitive and resistant parasites differentially utilize scavenging and biosynthetic pathways for multiple essential metabolites including folate and polyamines, and others within the mitochondria. Our findings are consistent with experimental literature, while generating novel hypotheses about artemisinin resistance and parasite biology. We detect evidence that resistance parasites maintain greater metabolic flexibility, perhaps representing an incomplete transition to the metabolic state most appropriate for nutrient-rich blood.CONCLUSIONUsing this systems biology approach, we identify metabolic shifts that arise with or in support of the resistant phenotype. This perspective allows us to more productively analyze and interpret clinical expression data for the identification of candidate drug targets for the treatment of resistant parasites.
Sustainability and cost assessment of coastal vacation homes for energy retrofits
Authors: Panthi Kamalesh , Das Kanchan , Abdel-Salam Tarek 
Published: March 2017

Purpose
Vacation rental homes, in general, have different energy usage characteristics than traditional residential homes mainly because of the occupancy pattern that changes on a weekly basis. These homes, predominantly larger in size, offer a greater scope for energy savings also because of the wasteful habits of their seasonal occupants. The purpose of this paper is to investigate the causes of energy inefficiencies prevalent in these homes so that appropriate retrofit choices can be offered to homeowners.

Design/methodology/approach
This research presents a case study of a vacation rental home whose energy consumption was investigated in depth and energy inefficiencies identified through modeling using energy modeling software, eQUEST. Simulations were performed to identify viable retrofit scenarios.

Findings
While improvement in the building envelope such as providing shades/overhangs on the windows, reducing infiltration and increasing insulation of the exterior wall did not show promising results for savings on energy cost, other improvements such as use of highly efficient lamps, tank-less water heater system and occupancy sensors showed viable investment options with shorter payback periods. It was also found that energy use intensity of sampled houses was about half of the average of US residential buildings, which could primarily be attributed to the seasonal nature of occupancy of these houses.

Originality/value
There is a dearth of literature pertaining to energy efficiency-related retrofits of coastal vacation homes. This research fills that gap to some extent by addressing this issue with an ultimate aim of assisting homeowners in retrofit decision-making.
Developing labour productivity norms for aluminium system formwork in Sri Lanka
Authors: Senarath Jayasinghe Ruchini , Fernando Nirodha Gayani 
Published: March 2017

Purpose
The purpose of this paper is to establish labour productivity norms (LPNs) on an elemental basis to investigate a measurement for the labour productivity (LP) of aluminium system formwork (ASF) in low-cost housing projects (LHPs) in Sri Lanka.

Design/methodology/approach
Case study approach was selected as the most appropriate for the study and semi-structured interviews, document review and direct observations were used for the data collection. Four case studies were conducted. Eight semi-structured interviews were conducted among four cases. Further, document review was used in three cases, and direct observation was used in one case. The validation of the results was not possible in a real life project due to time limitations.

Findings
The findings identified six labour productivity factors (LPFs) affecting the LP of ASF. The need for LPNs for ASF on an elemental basis is identified. Further, LPNs were developed using LPFs.

Research limitations/implications
This research was limited to LHPs for underserved settlements in Colombo, Sri Lanka which use ASF. The LPNs were prepared based on time studies and were restricted to structural elements such as slabs, beams and columns.

Originality/value
The LPNs were developed for ASF in LHPs based on the effect of weather, crew, site, management and project factors. Further, the study addresses a gap in the literature regarding the development of LPNs of ASF for LPHs in Sri Lanka. LPNs for ASF have enhanced LP while promoting economic and social stability in the industry.
Review of project planning methods for deconstruction projects of buildings
Authors: Hübner Felix , Volk Rebekka , Kühlen Anna , Schultmann Frank 
Published: March 2017

Purpose
The purpose of this paper is to provide a comprehensive overview of literature and methods that can be used for deconstruction project planning of buildings. Furthermore, shortcomings of the identified planning methods are presented and research gaps are identified.

Design/methodology/approach
Requirements to consider for the planning of deconstruction projects are defined, to help in the classification of planning methods. With the help of these requirements, in a detailed literature review strategic and operational planning methods for deconstruction projects are investigated and discussed. Requirements which are not met by any of the identified planning methods can be interpreted as research and/or documentation gaps.

Findings
On the one hand, the literature review shows that recent approaches deal with planning methods for deterministic time and resource scheduling. Furthermore, project costs can be well planned by several methods. On the other hand, the literature review reveals that recent approaches mostly do not consider risks and uncertainties, environmental hazards or specific safety issues. A major shortcoming is that applied planning methods can only calculate up to a specific level of detail, e.g. with a limited number of activities, due to a very high computational effort in solving such project planning problems exactly.

Originality/value
To the authors’ knowledge, this is the first study that provides an overview of literature and methods for the deconstruction project planning of buildings and it is also the first study that unveils research gaps for future research. Furthermore, the classified planning methods assist in identifying suitable methods for the planning of future deconstruction projects.
Highly cited articles in malaria research: a bibliometric analysis
Authors: Kolle Shankar Reddy , Vijayashree M.S. , Shankarappa T.H. 
Published: March 2017

PurposeThe purpose of this paper is to reveal the bibliometric characteristics of highly cited articles in Malaria research for the period of 1991-2015.Design/methodology/approachThe data of highly cited articles for the period of 1991 to 2015 were extracted from the Science Citation Index Expended of Web of Science. The keyword “Malaria” was used as topic term to search documents that contained this word in the title or keyword or abstract of the documents that published in 1991 to 2015. A total of 1,614 articles having TC2015= 100 were retrieved as highly cited articles for further analysis, and Microsoft excel was used for the analysis purpose.FindingsA total of 1,614 of highly cited articles were published in the 230 journals for the period of 1991 to 2015, and majority of the articles were appeared in journals that have top impact factor. The articles published in the 2011s have greater average citations and authors per article. Six journals have produced almost a quarter of highly cited articles and remaining articles were published in 224 journals. Proceedings of the National Academy of Sciences of the USA was the most productive journal with 154 articles, which accounts for 9.53 per cent of the total articles, followed by Lancet (110; 6.81 per cent). We found degree collaboration value of 0.971 for the articles, which indicates the clear dominance of multiple authors in publication of highly cited articles in Malaria research. In this study, new indictor calledPindex was applied for the evaluation of the author’s productivity. As per thep-value, the White, NJ has emerged as the most productive author with thep-value of 0.41 (61 articles), followed by Marsh, K (p= 0.33), Nosten, F (p= 0.32) and Snow, RW (p= 0.31). The USA and the UK were the most productive countries. The article entitled as “Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data” contributed by Lopezet al.(2006) was the most cited article with 2,245 citations in 2015.Research limitations/implicationsThe data for the present study was limited to the publications that indexed in Science Citation index Expended of Web of Science.Originality/valueThis paper would be useful to the researchers to know the trends and achievements in the Malaria research and also to the library and information science professionals in collection building process.
CORE PDS: empowering the poor
Authors: Sharma Namrata , Sahay B.S. , Sarma PRS 
Published: March 2017

Structured abstract
Subject area information and communication technology (ICT) for development.

Study level/applicability
Master of Business Administration Program’s Management Information Systems courses. Or introductory courses in Masters in ICT for Development.

Case overview
The paper aims to highlight the endeavour of public distribution system (PDS), a food security scheme for under-privileged people in India, towards excellence, using ICT in the state of Chhattisgarh. It presents two important roles of ICT: one, as a system improvement tool, through supply chain integration (in Phase 1) and, the other, as tool for empowerment, by providing choices through computerized online real-time electronic (CORE) PDS (in Phase 2). CORE PDS was intended to provide choices of retail outlets to poor beneficiaries for collecting their food entitlement, breaking the retail outlet’s monopoly. The project was successfully implemented in some urban areas of Chhattisgarh, providing motivation for its mass scale roll-out. But, the contextual differences between rural and urban settings were raising questions on the ultimate value expected to be delivered by the project in rural areas.

Expected learning outcomes
Two major learning outcomes of the case: students will appreciate the multi-faceted role of ICT in improving the performance of a system meant for a financially poor section of the society; students will understand the role of contextual settings in a developing economy in the endeavour of ICT projects for societal development.

Supplementary materials
Teaching notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS 10: Public Sector Management.
Incubator or accelerator – a tech start-up’s dilemma
Authors: Shankar Raj K. 
Published: March 2017

Subject area
Entrepreneurship; Technology Transfer; Incubators; Accelerators

Study level/applicability
Postgraduate, Faculty Development Programs (FDP) and Management Development Programs (MDP) in areas of Technology Entrepreneurship, Entrepreneurship Education, Incubator and Accelerator Management.

Case overview
Madras Mind Works Private Limited (MMW) is an entrepreneurial venture set up by four friends in Chennai (earlier known as Madras) in Tamil Nadu, India. MMW intends to use the emerging trends in virtual reality and exploit opportunities that arise from its application. MMW has received invitations to join both an incubator as well as an accelerator. After detailed deliberations among the four co-founders that yielded no conclusion, the team left the responsibility of taking the decision to its Chief Executive Officer (CEO), Srinivasan Krish (Srini). Srini now has to decide whether MMW must join the incubator or the accelerator.

Expected learning outcomes
At least five factors will be learnt based on which tech start-ups can decide whether they should join an incubator or accelerator. Two important players in the entrepreneurship ecosystem are incubators and accelerators. You will learn to define them, describe their characteristics and services and learn their similarities and differences. You will learn what constitutes an entrepreneurial ecosystem using the BEEP framework. You will learn about many ecosystem players including but not limited to – incubators, accelerators, co-working spaces, technology transfer offices, research parks, angels, venture capitalists, government support schemes, university research centres, etc.

Supplementary materials
Board Plans, YouTube Video Links.

Subject code
CSS 3: Entrepreneurship.