bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integration of human pancreatic islet genomic data refines regulatory mechanisms at Type 2 Diabetes susceptibility loci
Authors: Thurner Matthias , Bunt Martijn van de , Torres Jason M , Mahajan Anubha , Nylander Vibe , Bennett Amanda J , Gaulton Kyle , Barrett Amy , Burrows Carla , Bell Christopher G , Lowe Robert , Beck Stephan , Rakyan Vardhman K , Gloyn Anna L , McCarthy Mark I 
Published: September 2017

AbstractHuman genetic studies have emphasised the dominant contribution of pancreatic islet dysfunction to development of Type 2 Diabetes (T2D). However, limited annotation of the islet epigenome has constrained efforts to define the molecular mechanisms mediating the, largely regulatory, signals revealed by Genome-Wide Association Studies (GWAS). We characterised patterns of chromatin accessibility (ATAC-seq, n=17) and DNA methylation (whole-genome bisulphite sequencing, n=10) in human islets, generating high-resolution chromatin state maps through integration with established ChIP-seq marks. We found enrichment of GWAS signals for T2D and fasting glucose was concentrated in subsets of islet enhancers characterised by open chromatin and hypomethylation, with the former annotation predominant. At several loci (includingCDC123,ADCY5,KLHDC5) the combination of fine-mapping genetic data and chromatin state enrichment maps, supplemented by allelic imbalance in chromatin accessibility pinpointed likely causal variants. The combination of increasingly-precise genetic and islet epigenomic information accelerates definition of causal mechanisms implicated in T2D pathogenesis.
Efficient management and analysis of large-scale genome-wide data with two R packages: bigstatsr and bigsnpr
Authors: Privé Florian , Aschard Hugues , Blum Michael G.B. 
Published: September 2017

AbstractMotivation:Genome-wide datasets produced for association studies have dramatically increased in size over the past few years, with modern datasets commonly including millions of variants measured in dozens of thousands of individuals. This increase in data size is a major challenge severely slowing down genomic analyses. Specialized software for every part of the analysis pipeline have been developed to handle large genomic data. However, combining all these software into a single data analysis pipeline might be technically difficult.Results:Here we present two R packages, bigstatsr and bigsnpr, allowing for management and analysis of large scale genomic data to be performed within a single comprehensive framework. To address large data size, the packages use memory-mapping for accessing data matrices stored on disk instead of in RAM. To perform data pre-processing and data analysis, the packages integrate most of the tools that are commonly used, either through transparent system calls to existing software, or through updated or improved implementation of existing methods. In particular, the packages implement a fast derivation of Principal Component Analysis, functions to remove SNPs in Linkage Disequilibrium, and algorithms to learn Polygenic Risk Scores on millions of SNPs. We illustrate applications of the two R packages by analysing a case-control genomic dataset for the celiac disease, performing an association study and computing Polygenic Risk Scores. Finally, we demonstrate the scalability of the R packages by analyzing a simulated genome-wide dataset including 500,000 individuals and 1 million markers on a single desktop computer.Availability:https://privefl.github.io/bigstatsr/&https://privefl.github.io/bigsnpr/Contact:florian.prive@univ-grenoble-alpes.fr&michael.blum@univ-grenoble-alpes.frSupplementary information:Supplementary data are available atBioinformaticsonline.
A novel combination of chemotherapy and immunotherapy controls tumor growth in mice with a human immune system
Authors: Burlion Aude , Ramos Rodrigo N. , Pukar KC , Sendeyo Kélhia , Corneau Aurélien , Ménétrier-Caux Christine , Piaggio Eliane , Olive Daniel , Caux Christophe , Marodon Gilles 
Published: September 2017

AbstractMice reconstituted with a human immune system and bearing human tumors represent a promising model for developing novel cancer immunotherapies. Here, we used mass cytometry and multi-parametric flow cytometry to characterize human leukocytes infiltrating a human breast cancer tumor model in immunocompromised NOD.SCID.γc-null mice reconstituted with a human immune system and compared it to samples of breast cancer patients. We observed highly activated human CD4+and CD8+T cells in the tumor, as well as minor subsets of innate immune cells in both settings. We also report that ICOS+CD4+regulatory T cells (Treg) were enriched in the tumor relative to the periphery in humanized mice and patients, providing a target to affect Treg and tumor growth. Indeed, administration of a neutralizing mAb to human ICOS reduced Treg proportions and numbers and improved CD4+ T cell proliferation in humanized mice. Moreover, a combination of the anti-ICOS mAb with cyclophosphamide reduced tumor growth, and that was associated with an improved CD8 to Treg ratio. However, depletion of human CD8+T cells only marginally affected tumor control whereas depletion of murine myeloid cells abrogated the effect of the combination therapy. Altogether, our results indicate that a combination of anti-ICOS mAb and chemotherapy controls tumor growth in humanized mice and highlight the crucial implication of innate immunity in treatment efficacy, opening new perspectives for the treatment of breast cancer.One sentence summaryICOS expressed on Tregs is a promising target to improve tumor immunity in humansAbbreviationsICOSInducible CostimulatoryNSGNOD.SCID.gc-nullTregregulatory T cellsCTXcyclophosphamideHuMicehumanized miceCyTOFcytometry time-of-flighttSNEtdistributed stochastic neighbor embeddingpDCsplasmacytoid dendritic cellsDCdendritic cellsICDimmunogenic cell death
Curated compendium of human transcriptional biomarker data
Authors: Golightly Nathan P. , Bischoff Anna I. , Bell Avery , Hollingsworth Parker D. , Piccolo Stephen R. 
Published: September 2017

AbstractGenome-wide transcriptional profiles provide broad insights into cellular activity. One important use of such data isto identify relationships between transcription levels and patient outcomes. These translational insights can guide the development of biomarkers for predicting outcomes in clinical settings. Over the past decades, data from many translational-biomarker studies have been deposited in public repositories, enabling other scientists to reuse the data in follow-up studies. However, data-reuse efforts require considerable time and expertise because transcriptional data are generated using heterogeneous profiling technologies, preprocessed using diverse normalization procedures, and annotated in non-standard ways. To address this problem, we curated a compendium of 45 translational-biomarker datasets from the public domain. To increase the data’s utility, we reprocessed the raw expression data using a standard computational pipeline and standardized the clinical annotations in a fully reproducible manner (seeosf.io/ssk3t). We believe these data will be particularly useful to researchers seeking to validate gene-level findings or to perform benchmarking studies—for example, to compare and optimize machine-learning algorithms’ ability to predict biomedical outcomes.
Internal resources as tools to increase the global competition: the Italian wine industry case
Authors: Galati Antonino , Crescimanno Maria , Tinervia Salvatore , Iliopoulos Constantine , Theodorakopoulou Irini 
Published: September 2017

Purpose
The purpose of this paper is twofold: first, it identifies distinct organizational models in a sample of small and medium enterprises operating in the Sicilian wine industry; and second, it identifies the key factors enabling a superior export success.

Design/methodology/approach
Internal resources were analyzed theoretically in order to achieve the aims of the study. Subsequently the empirical investigation was carried out administering a questionnaire to a sample of 102 wineries in Sicily, Italy. A cluster analysis was performed in order to group these firms into homogeneous categories.

Findings
The findings show that success in the international market is more common among wineries characterized by a larger physical and economic size, a longer experience in the international market, managed by entrepreneurs-owners who are highly educated and proficient in foreign language, and implement voluntary certifications.

Research limitations/implications
The results need to be interpreted within the context of the study’s research design; more specifically, the reader should take into account that the study focuses exclusively on one industry and on one region (wine in Sicily).

Practical implications
The findings offer a valid support for managers who could use this results to better focus their effort and choose the most appropriate strategy in order to improve their performance in foreign markets.

Originality/value
Very few empirical studies have been carried out on the impact that internal and in particular organizational resources have on the firms’ organizational models operating in the wine industry.
Lean production and supply chain innovation in baked foods supplier to improve performance
Authors: Shah Satya R. , Naghi Ganji Elmira 
Published: September 2017

Purpose
Service industries are currently facing an excess of overproduction that results in extra inventory and waste levels. With the prospect of methods such as lean production, the purpose of this paper is to investigate the impacts of lean production methods towards enhanced performance of service-based industries through the study of a local baked foods supplier.

Design/methodology/approach
The paper highlights the first stage of research study through current world literature and a critical review as inputs of research findings. The research applies a descriptive research framework within a semi-structured questionnaire survey method which was implemented within three different companies, the baked goods manufacturer, the cafe purchasing the baked foods products and the end users, hence covering the overall supply chain cycle and its entities.

Findings
The research study identified that one of the major challenges facing the baked food company when adopting the lean practices was the lack of commitment from the top management, continuous training, and hence, employee engagement measures were necessary towards performance improvement of the organisation.

Originality/value
The research novelty is to develop an early understanding of lean production practices within the baked goods manufacturer and its upstream and downstream stakeholders. This paper would be considered by the food manufacturer companies in order to require their key suppliers to adopt the most common lean tools identified as Just in Time, Value Steam Mapping and the 5S methods.
Business model configuration and dynamics for technology commercialization in mature markets
Authors: Flammini Serena , Arcese Gabriella , Lucchetti Maria Claudia , Mortara Letizia 
Published: September 2017

PurposeThe food industry is a well-established and complex industry. New entrants attempting to penetrate it via the commercialization of a new technological innovation could face high uncertainty and constraints. The capability to innovate through collaboration and to identify suitable strategies and innovative business models (BMs) can be particularly important for bringing a technological innovation to this market. However, although the potential for these capabilities has been advocated, we still lack a complete understanding of how new ventures could support the technology commercialization process via the development of BMs. The paper aims to discuss these issues.Design/methodology/approachTo address this gap, this paper builds a conceptual framework that knits together the different bodies of extant literature (i.e. entrepreneurship, strategy and innovation) to analyze the BM innovation processes associated with the exploitation of emerging technologies; determines the suitability of the framework using data from the exploratory case study of IT IS 3D – a firm which has started to exploit 3D printing in the food industry; and improves the initial conceptual framework with the findings that emerged in the case study.FindingsFrom this analysis it emerged that: companies could use more than one BM at a time; hence, BM innovation processes could co-exist and be run in parallel; the facing of high uncertainty might lead firms to choose a closed and/or a familiar BM, while explorative strategies could be pursued with open BMs; significant changes in strategies during the technology commercialization process are not necessarily reflected in a radical change in the BM; and firms could deliberately adopt interim strategies and BMs as means to identify the more suitable ones to reach the market.Originality/valueThis case study illustrates how firms could innovate the processes of their BM development to face the uncertainties linked with the entry into a mature and highly conservative industry (food).
Street food and innovation: the food truck phenomenon
Authors: Alfiero Simona , Lo Giudice Agata , Bonadonna Alessandro 
Published: September 2017

PurposeThe purpose of this paper is to focus on food truck phenomenon, a particular kind of street food service, identifying two categories of performers: “Traditional Food Truck” (TFT) and “Gourmet Food Truck” (GFT). This paper evaluates and compares the efficiency performance of the main actors.Design/methodology/approachA sample of 41 food trucks in the Northwest of Italy was identified. A survey was carried out to determine the characteristics of the food truck and evaluate the efficiency performance of an output-oriented data envelopment analysis.FindingsThe two kinds of food trucks provide different levels of efficacy: the data showed that 22 per cent of the food trucks operate efficiently with an average efficiency score of 0.80. The results demonstrate that GFT are more efficient than TFT and confirm that innovation is an important key to competitive advantage in this sector.Research limitations/implicationsThe data collected were related only to the food truckers that operate in the Turin area and the number of variables analysed is limited to certain aspects of production and selling processes.Practical implicationsThe results provided some managerial indicators to improve the level of corporate efficiency, operating on technical decisions.Originality/valueThis is a pioneer study that analyses how a business based on the combination of tradition and innovation can offer a competitive advantage and strengthen a strong connection to its territory, improving corporate performance.
Value maximization and open innovation in food and beverage industry: evidence from US market
Authors: Miglietta Nicola , Battisti Enrico , Campanella Francesco 
Published: September 2017

PurposeThe purpose of this paper is to examine listed companies, grouped by sector, that for decades have shown a dividend growth. Referring to the food and beverage (F&B) industry, the authors have investigated the adoption of an open innovation model in order to fill a gap in the existing literature.Design/methodology/approachThis paper uses a multi-method design linking qualitative and quantitative approaches. The quantitative study was planned in order to identify some US-listed companies, called Dividend Champions that have distributed consistently growing dividends for over 50 years and have beaten the markets. The qualitative study was designed to provide insight into the adoption or not of an open innovation model by the listed companies in the F&B industry in the US market that were selected by the quantitative analysis.FindingsThe research is based on an empirical analysis undertaken with 816 listed companies in US markets. In particular, the authors underline 20 companies that over the past 50 years have systematically increased dividend paid, and at the same time, have beaten the market (Standard & Poor’s 500). In all, 30 per cent of the selected companies belong to the consumer goods sector, and F&B companies represent 50 per cent of them. All of these companies (The Coca-Coca Company, Hormel Foods Corporation, and Lancaster Colony Corporation) implement an open innovation model.Originality/valueTo the authors’ knowledge, this is the first exploratory study based on value maximisation and open innovation. An open innovation model increases competitiveness and the durability of competitive advantage, which are main sources of value creation. The paper highlights evidence from the F&B industry, referred to as Dividend Champions, and the adoption of an open innovation model.
From space food research and innovation to immediate advantages for Earth eating habits
Authors: Varese Erica , Cane Paola 
Published: September 2017

PurposeThe purpose of this paper is to analyse how the food innovation strategies carried out by an Italian firm, Argotec, responsible for the development and supply of space food (SF) for European astronauts on the International Space Station (ISS), can also be applied to food suitable to be eaten on Planet Earth. This study aims at showing the relationship between SF innovation and terrestrial strategies directed at implementing this kind of food also on terrestrial tables.Design/methodology/approachThis research focusses on a case study. The subject of the case study under analysis is Argotec, an internationally recognised Italian aerospace engineering company, dealing with research, innovation and development in various sectors, including engineering, information technology, system integration, small satellites and “Human Space Flight and Operations”. The company produces innovative SF for European astronauts performing long-duration missions on-board the ISS. Moreover, the SF is made available also for terrestrial beings as a solution for everyday eating necessities.FindingsArgotec is characterised by strong innovation in terms of products and processes. Throughout the case study, the authors focus on the relationship between SF innovation and its terrestrial applications, since this company also manufactures products, traded under the brand “ReadyToLunch”, suitable for daily meals on Earth. Innovation applied to SF can thus offer advantages also for terrestrial daily meals and therefore help the company achieve other competitive advantages: as to the authors’ knowledge, this is a unique case.Research limitations/implicationsThis study also has some limitations, typical of the applied methodology. In relation to the interview technique, further interviews would be required in order to fully understand the end-user perspectives regarding the importance and interest of this kind of “ready-to-eat” food.Practical implicationsPractical implications relate to astronauts and to terrestrial consumers. For astronauts, SF is not any more intended only to satisfy humans’ basic needs, and to provide the necessary nutrients during space missions, but has become an important factor in the quality of life in space. For terrestrial consumers, SF may represent a healthy, tasty and nutritious “ready-to-eat” choice: single courses for the main meals and snacks for a break.Originality/valueThis research fills a gap in literature: to the authors’ knowledge, this is the first paper presenting a case study on a company responsible for the development and supply of SF for European astronauts on-board the ISS, as well as encouraging the consumption of SF by terrestrial beings, as an ordinary “ready-to-eat” lunch/dinner.
Sanitation, human rights and disaster management
Authors: Aronsson-Storrier Marie 
Published: September 2017

Purpose
The purpose of this paper is to link debates around the international law on human rights and disaster management with the evolving debate around the human right to sanitation, in order to explore the extent to which states are obliged to account for sanitation in their disaster management efforts.

Design/methodology/approach
The paper is based on analysis of existing laws and policy relating to human rights, sanitation and disaster management. It further draws upon relevant academic literature.

Findings
The paper concludes that, while limitations exist, states have legal obligations to provide sanitation to persons affected by a disaster. It is further argued that a human rights-based approach to sanitation, if respected, can assist in strengthening disaster management efforts, while focusing on the persons who need it the most.

Research limitations/implications
The analysis in this paper focuses on the obligations of states for people on their territory. Due to space limitations, it does not examine the complex issues relating to enforcement mechanisms available to disaster victims.

Originality/value
This is the first scholarly work directly linking the debates around international human rights law and disaster management, with human rights obligations in relation to sanitation. The clarification of obligation in relation to sanitation can assist in advocacy and planning, as well as in ensuring accountability and responsibility for human rights breaches in the disaster context.
Disasters and non-state actors – human rights-based approaches
Authors: Hesselman Marlies , Lane Lottie 
Published: September 2017

Purpose
The purpose of this paper is to examine the roles and responsibilities of non-state actors (NSAs) in contributing to disaster governance from an international human rights law (IHRL) perspective. In particular, it examines how non-governmental organizations (NGOs) and business enterprises are implicated.

Design/methodology/approach
The paper analyzes a range of IHRL instruments, particularly treaties and international soft-law documents, and it utilizes the concepts “human rights-based approaches” (HRBAs) and “direct”/“indirect” human rights obligations to frame and understand how IHRL responsibilities for NSAs arise from these instruments.

Findings
IHRL not only includes relevant standards for NSAs in the area of disaster management, but NGOs and businesses also actively engage with IHRL and HRBAs by means of (soft) self-regulatory instruments to further clarify their responsibilities.

Research limitations/implications
The findings are of interest to all actors involved in disaster governance, and are instructive for NGOs and businesses seeking to improve the design of disaster management activity. The research addresses only the responsibility of NGOs and private companies, but the framework of analysis set out is equally of interest to other actors’ activities.

Originality/value
The implications of IHRL for NSAs involved in disaster management are still poorly understood, despite their vast engagement. This study contributes by clarifying the roles and IHRL responsibilities of NGOs and businesses specifically, and articulates how applications of HRBAs may improve the protection of persons.