bluuebunny/crossref_metadata_2025_split huggingface dataset:
DeepAffinity: Interpretable Deep Learning of Compound-Protein Affinity through Unified Recurrent and Convolutional Neural Networks
Authors: Karimi Mostafa , Wu Di , Wang Zhangyang , shen Yang 
Published: June 2018

AbstractMotivationDrug discovery demands rapid quantification of compound-protein interaction (CPI). However, there is a lack of methods that can predict compound-protein affinity from sequences alone with high applicability, accuracy, and interpretability.ResultsWe present a seamless integration of domain knowledges and learning-based approaches. Under novel representations of structurally-annotatedprotein sequences, a semi-supervised deep learning model that unifies recurrent and convolutional neural networks has been proposed to exploit both unlabeled and labeled data, for jointly encoding molecular representations and predicting affinities. Our representations and models outperform conventional options in achieving relative error in IC50 within 5-fold for test cases and 20-fold for protein classes not included for training. Performances for new protein classes with few labeled data are further improved by transfer learning. Furthermore, separate and joint attention mechanisms are developed and embedded to our model to add to its interpretability, as illustrated in case studies for predicting and explaining selective drug-target interactions. Lastly, alternative representations using protein sequences or compound graphs and a unified RNN/GCNN-CNN model using graph CNN (GCNN) are also explored to reveal algorithmic challenges ahead.AvailabilityData and source codes are available at https://github.com/Shen-Lab/DeepAffinityContactyshen@tamu.eduSupplementary informationSupplementary data are available at http://shen-lab.github.io/deep-affinity-bioinf18-supp-rev.pdf.
An epitope-resurfaced virus-like particle can induce broad neutralizing antibody against four serotypes of dengue virus
Authors: Shen Wen-Fan , Ucat Galula Jedhan , Liu Jyung-Hurng , Liao Mei-Ying , Huang Chang-Hao , Wang Yu-Chun , Wu Han-Chung , Liang Jian-Jong , Lin Yi-Ling , Whitney Matthew T. , Chang Gwong-Jen J. , Chen Sheng-Ren , Wu Shang-Rung , Chao Day-Yu 
Published: June 2018

AbstractDengue fever is caused by four different serotypes of dengue virus (DENV) which is the leading cause of worldwide arboviral diseases in humans. Virus-like particles (VLPs) containing flavivirus prM/E proteins have been demonstrated to be a potential vaccine candidate; however, the structure of dengue VLP is poorly understood. Herein we show for the first time that mD2VLP particles possess a T=1 icosahedral symmetry with a groove located within the E-protein dimers near the 2-fold vertices that exposed highly overlapping, cryptic neutralizing epitopes through cryo-electron microscopy reconstruction. Mice vaccinated with highly matured virus-like particles derived from DENV serotype 2 (mD2VLP) can generate higher cross reactive (CR) neutralization antibodies (NtAbs) and were protected against all 4 serotypes of DENV through clonal expansion supported by hybridoma and B-cell repertoire analysis. Our results revealed that a “epitope-resurfaced” mature-form dengue VLP has the potential to induce quaternary structure-recognizing broad CR NtAbs.
Target localization across saccades and at fixation: Nontargets both facilitate and bias responses
Authors: Zhang Xiaoli , Golomb Julie D. 
Published: June 2018

AbstractThe image on our retina changes every time we make an eye movement. To maintain visual stability across saccades, specifically to locate visual targets, we may use nontarget objects as “landmarks”. In the current study, we compared how the presence of nontargets affects target localization across saccades and during sustained fixation. Participants fixated a target object, which either maintained its location on the screen (sustained-fixation trials), or displaced to trigger a saccade (saccade trials). After the target disappeared, participants reported the most recent target location with a mouse click. We found that the presence of nontargets decreased response error magnitude and variability. However, this nontarget facilitation effect was not larger for saccade trials than sustained-fixation trials, indicating that nontarget facilitation might be a general effect for target localization, rather than of particular importance to saccadic stability. Additionally, participants’ responses were biased towards the nontarget locations, particularly when the nontarget-target relationships were preserved in relative coordinates across the saccade. This nontarget bias interacted with biases from other spatial references, e.g. eye movement paths, possibly in a way that emphasized non-redundant information. In summary, the presence of nontargets is one of several sources of reference that combine to influence (both facilitate and bias) target localization.
The MS4A gene cluster is a key regulator of soluble TREM2 and Alzheimer disease risk
Authors: Deming Yuetiva , Filipello Fabia , Cignarella Francesca , Cantoni Claudia , Hsu Simon , Mikesell Robert , Li Zeran , Del-Aguila Jorge L , Dube Umber , Farias Fabiana Geraldo , Bradley Joseph , Benitez Bruno , Budde John , Ibanez Laura , Fernandez Maria Victoria ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI),   Dominantly Inherited Alzheimer Network (DIAN), Blennow Kaj , Zetterberg Henrik , Heslegrave Amanda , Johansson Per M , Svensson Johan , Nellgård Bengt , Lleo Alberto , Alcolea Daniel , Clarimon Jordi , Rami Lorena , Molinuevo José Luis , Suarez-Calvet Marc , Morenas-Rodríguez Estrella , Kleinberger Gernot , Ewers Michael , Harari Oscar , Haass Christian , Brett Thomas J , Karch Celeste M. , Piccio Laura , Cruchaga Carlos 
Published: June 2018

AbstractSoluble triggering receptor expressed on myeloid cells 2 (sTREM2) levels in the cerebrospinal fluid (CSF) have been associated with Alzheimer disease (AD) status. TREM2 plays a critical role in microglial activation, survival, and phagocytosis; however, the pathophysiological role of sTREM2 in AD is not well understood. Understanding the role of sTREM2 in AD may help reveal biological mechanisms underlying AD and identify novel therapeutic targets. We performed a genome-wide association study (GWAS) to identify genetic modifiers of CSF sTREM2 levels. Common variants in the membrane-spanning 4-domains subfamily A (MS4A) gene region were associated with higher CSF sTREM2 levels (rs1582763; P = 1.15×10−15) and replicated in independent datasets. The variants associated with increased levels of sTREM2 are also associated with reduced AD risk and delayed age-at-onset. Rs1582763 influences expression of MS4A4A and MS4A6A in multiple tissues, suggesting that one or both of these genes are important for regulating sTREM2. MS4A genes encode transmembrane proteins that may play a role in intracellular protein trafficking in microglia. We used human macrophages to begin to test the relationship between MS4A4A and TREM2 and found that they co-localize intracellularly and that antibody-mediated targeting of MS4A4A reduces sTREM2. Thus, genetic, molecular, and cellular findings suggest that MS4A4A regulates sTREM2. These findings also provide a mechanistic explanation of the original GWAS signal in the MS4A locus for AD risk and indicate that TREM2 is involved in sporadic AD risk in general, not only in TREM2 risk-variant carriers.
Robust genome editing with short single-stranded and long, partially single-stranded DNA donors in C. elegans
Authors: Dokshin Gregoriy A. , Ghanta Krishna S. , Piscopo Katherine M. , Mello Craig C. 
Published: June 2018

AbstractCRISPR-based genome editing using ribonucleoprotein (RNP) complexes and synthetic single stranded oligodeoxynucleotide (ssODN) donors can be highly effective. However, reproducibility can vary, and precise, targeted integration of longer constructs – such as green fluorescent protein (GFP) tags remains challenging in many systems. Here we describe a streamlined and optimized editing protocol for the nematode C. elegans. We demonstrate its efficacy, flexibility, and cost-effectiveness by affinity-tagging all twelve of the Worm-specific Argonaute (WAGO) proteins in C. elegans using ssODN donors. In addition, we describe a novel PCR-based partially single-stranded “hybrid” donor design that yields high efficiency editing with large (kilobase-scale) constructs. We use these hybrid donors to introduce fluorescent protein tags into multiple loci achieving editing efficiencies that approach those previously obtained only with much shorter ssODN donors. The principals and strategies described here are likely to translate to other systems and should allow researchers to reproducibly and efficiently obtain both long and short precision genome edits.
A highly predictive signature of cognition and brain atrophy for progression to Alzheimer’s dementia
Authors: Tam Angela , Dansereau Christian , Itturia-Medina Yasser , Urchs Sebastian , Orban Pierre , Sharmarke Hanad , Breitner John , Bellec Pierre ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: June 2018

AbstractClinical trials in Alzheimer’s disease need to enroll patients whose cognition will decline over time, if left untreated, in order to demonstrate the efficacy of an intervention. Machine learning models used to screen for patients at risk of progression to dementia should therefore favor specificity (detecting only progressors) over sensitivity (detecting all progressors), especially when the prevalence of progressors is low. Here, we explore whether such high-risk patients can be identified using cognitive assessments and structural neuroimaging, by training machine learning tools in a high specificity regime. A multimodal signature of Alzheimer’s dementia was first extracted from ADNI1. We then validated the predictive value of this signature on ADNI1 patients with mild cognitive impairment (N=235). The signature was optimized to predict progression to dementia over three years with low sensitivity (55.1%) but high specificity (95.6%), resulting in only moderate accuracy (69.3%) but high positive predictive value (80.4%, adjusted for a “typical” 33% prevalence rate of true progressors). These results were replicated in ADNI2 (N=235), with 87.8% adjusted positive predictive value (96.7% specificity, 47.3% sensitivity, 85.1% accuracy). We found that cognitive measures alone could identify high-risk individuals, with structural measurements providing a slight improvement. The signature had comparable receiver operating characteristics to standard machine learning tools, yet a marked improvement in positive predictive value was achieved over the literature by selecting a high specificity operating point. The multimodal signature can be readily applied for the enrichment of clinical trials.
Happy home at Adform – corporate culture as a tool to attract and retain talent
Authors: Augutyte-Kvedaraviciene Ieva 
Published: June 2018

Subject area
Social science, Organizational behaviour.

Study level/applicability
The case is intended for bachelor or master level students as a part of HRM and OB curriculum and in particular organizational culture and change management topics as well as talent selection and innovation issues in the organization.

Case overview
Adform, a fast-growing global ad-tech company, is well-known in the market as a workplace that nurtures creativity and innovation. Recently recognized as the Aon Employer of the Year 2016 in the Baltic States by OVC, the company strives to maintain the position and remain an attractive place to work at. However, when both the sector and the company is growing fast, it becomes a challenge to sustain corporate culture and implement shared values in daily activities. Creative and innovative employees are in high demanded in the whole ad-tech sector and competition for the best professionals is inevitable. The key issues Anna, head of HR Strategic initiatives, is facing to present are as follows: How to attract and retain the best talent in a highly competitive labour market? How to maintain corporate culture that promotes innovative thinking when the company is growing fast and the sector is developing even faster? How to manage conflicts between personal and corporate values when employees are in high demand in the market? The case is structured from three different perspectives – newly employed professional Simon, experienced Adformers Ingrid and Martin, and Human Resources department specialists Anna and Sandra – everyone has different challenges and issues to solve; however, they share common values and beliefs, which form a sound base for decision-making and prove the importance of corporate culture as a strong management tool at Adform.

Expected learning outcomes
Expected learning outcomes are as follows: to understand major components of corporate culture and its role in an organisation, to gain practice in assessing corporate culture and its types; to understand the role of corporate culture in attracting and retaining talented employees to help company grow and develop; and to recognize challenges a company may encounter sustaining a strong corporate culture in a fast-growing sector and to analyse means of strong culture maintenance.

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: 6: Human Resource Management.
The impact of supply chain relationship quality on performance in the maritime logistics industry in light of firm characteristics
Authors: Shin Youngran , Thai Vinh , Yuen Kum Fai 
Published: June 2018

PurposeAnchoring on configuration theory, the purpose of this paper is to evaluate how supply chain relationship quality (SCRQ) differs across firm characteristics (FC) in the maritime logistics industry. In addition, it utilises transactional cost theory to establish the relationship between SCRQ and supply chain performance (SCP).Design/methodology/approachThe data were obtained from a survey with 205 maritime logistics service players (shipping firms, shippers and freight forwarders) in Singapore. MANOVA andt-test analyses are used to examine the difference in SCRQ (i.e. trust and commitment) across FC which includes firm types and ownership types. Thereafter, structural equation modelling is employed to examine the influence of SCRQ on SCP.FindingsThe results indicate that the effects of trust and commitment on SCRQ vary significantly. It was also found that trust as an aspect of SCRQ has a significant impact on SCP, whereas commitment does not.Research limitations/implicationsAs the field data were obtained from only one industry, future replication of the findings to other industries should consider industry-specific factors, if applicable.Practical implicationsIt is suggested that maritime logistics service players should carefully manage trust and commitment to simultaneously enable SCP. By identifying the various aspects of FC that contribute to SCRQ, maritime logistics service providers could devise appropriate strategies for different customer segments more effectively.Originality/valueThis study expands current supply chain research by linking two dimensions of SCRQ in relationship marketing with SCP in supply chain management. It is also one of the first empirical attempts to explore the role of FC in the linkage between SCRQ and SCP in the maritime logistics industry.
Stories and metaphors in retail selling
Authors: Gilliam David A. , Rockwell Casey C. 
Published: June 2018

PurposeThe purpose of this paper is to propose future directions for research into stories and metaphors as concise communication tools that are particularly salient for the fast pace of today’s retail sales environment.Design/methodology/approachA cross disciplinary approach is taken to propose new avenues for sales communication research.FindingsThis work highlights research possibilities into the contextually sensitive constructs of stories and metaphors with associated theoretical approaches. This could improve research into stories and metaphors as communication techniques for retail selling.Research limitations/implicationsThe findings indicate that stories and metaphors are highly engaging sensemaking tools that salespeople can use in retail sales encounters. The lack of existing literature within the sales domain suggests a significant learning curve in demarcating the use of these tools.Practical implicationsStories and metaphors are presently used by salespeople but without the benefit of extensive scientific understanding. This paper builds a foundation for research that could bring clarity to the use of these tools in retail selling.Originality/valueResearchers will benefit from a finer grained conceptualization with which to examine sales communication. The proposed research should get sales practitioners a clearer understanding of using stories and metaphors in sales encounters.
Indexing Arabic texts using association rule data mining
Authors: Haraty Ramzi A. , Nasrallah Rouba 
Published: June 2018

Purpose
The purpose of this paper is to propose a new model to enhance auto-indexing Arabic texts. The model denotes extracting new relevant words by relating those chosen by previous classical methods to new words using data mining rules.

Design/methodology/approach
The proposed model uses an association rule algorithm for extracting frequent sets containing related items – to extract relationships between words in the texts to be indexed with words from texts that belong to the same category. The associations of words extracted are illustrated as sets of words that appear frequently together.

Findings
The proposed methodology shows significant enhancement in terms of accuracy, efficiency and reliability when compared to previous works.

Research limitations/implications
The stemming algorithm can be further enhanced. In the Arabic language, we have many grammatical rules. The more we integrate rules to the stemming algorithm, the better the stemming will be. Other enhancements can be done to the stop-list. This is by adding more words to it that should not be taken into consideration in the indexing mechanism. Also, numbers should be added to the list as well as using the thesaurus system because it links different phrases or words with the same meaning to each other, which improves the indexing mechanism. The authors also invite researchers to add more pre-requisite texts to have better results.

Originality/value
In this paper, the authors present a full text-based auto-indexing method for Arabic text documents. The auto-indexing method extracts new relevant words by using data mining rules, which has not been investigated before. The method uses an association rule mining algorithm for extracting frequent sets containing related items to extract relationships between words in the texts to be indexed with words from texts that belong to the same category. The benefits of the method are demonstrated using empirical work involving several Arabic texts.
Two cases of dabrafenib and trametinib therapy‐failed advanced melanoma successfully controlled by nivolumab monotherapy
Authors: Sato Yota , Fujimura Taku , Kambayashi Yumi , Tanita Kayo , Tono Hisayuki , Hashimoto Akira , Aiba Setsuya 
Published: June 2018

AbstractAlthough therapies for advanced melanoma have been greatly improved by the development of immune checkpoint inhibitors and BRAF/mitogen‐activated protein kinase kinase inhibitors, there are still many concerns about the administration of these novel drugs. Therefore, to combine these therapies sequentially at appropriate time points of the disease is important. In this report, we report two cases in which dabrafenib and trametinib therapy for advanced melanoma failed but were successfully controlled by nivolumab monotherapy, and investigated the sera sCD163, CCL22 and CXCL10 as biomarkers for tumor progression. Interestingly, the sera levels of sCD163, CXCL10 and CCL22, both of which are produced by activated tumor‐associated macrophages, were increased in parallel with the tumor progression in each case. Because this report presents only two cases, further data will need to be accumulated to provide more fundamental insights into the usefulness of these biomarkers for predicting disease progression in melanoma.
Inducible nitric oxide synthase inhibitor 1400W increases Na+,K+‐ATPase levels and activity and ameliorates mitochondrial dysfunction in Ctns null kidney proximal tubular epithelial cells
Authors: Sumayao Rodolfo , Newsholme Philip , McMorrow Tara 
Published: June 2018

SummaryNitric oxide (NO) has been shown to play an important role in renal physiology and pathophysiology partly through its influence on various transport systems in the kidney proximal tubule. The role of NO in kidney dysfunction associated with lysosomal storage disorder, cystinosis, is largely unknown. In the present study, the effects of inducible nitric oxide synthase (iNOS)‐specific inhibitor, 1400W, on Na+,K+‐ATPase activity and expression, mitochondrial integrity and function, nutrient metabolism, and apoptosis were investigated in Ctns null proximal tubular epithelial cells (PTECs). Ctns null PTECs exhibited an increase in iNOS expression, augmented NO and nitrite/nitrate production, and reduced Na+,K+‐ATPase expression and activity. In addition, these cells displayed depolarized mitochondria, reduced adenosine triphosphate content, altered nutrient metabolism, and elevated apoptosis. Treatment of Ctns null PTECs with 1400W abolished these effects which culminated in the mitigation of apoptosis in these cells. These findings indicate that uncontrolled NO production may constitute the upstream event that leads to the molecular and biochemical alterations observed in Ctns null PTECs and may explain, at least in part, the generalized proximal tubular dysfunction associated with cystinosis. Further studies are needed to realize the potential benefits of anti‐nitrosative therapies in improving renal function and/or attenuating renal injury in cystinosis.
Mutable environments and permeable human bodies★
Authors: Lock Margaret 
Published: June 2018

AbstractGeologists have declared an epochal transition to the Anthropocene, formally recognizing humans as the driving force of destructive global change; a distinction can no longer be made between human history and natural history. Certain commentators argue that Capitalocene better characterizes the situation, given that the effects of planetary decimation and global warming are not equally distributed among humans. A second conceptual change has recently taken place in which genomes are recognized as reactive to environmental stimuli both external and internal to the human body. In the post‐genomic era, genes neither initiate life nor drive human development. The science of the bourgeoning field of behavioural epigenetics is introduced, followed by illustrative examples of environmentally caused epigenetic changes that impact negatively on health. Epigeneticists routinely delimit their attention to detecting measurable changes at the molecular level. It is argued that anthropological contributions that incorporate subjective accounts of embodiment involving past and present events are crucial in order to better situate and account for biological differences and health outcomes historically, ecologically, and politically. Discussion of the microbiome provides a cautionary reminder that microbes are the ultimate driving force of health and illness. In conclusion, the Earth Optimism movement is briefly introduced, as is the concept of resilience, but alone these positive moves will not curb unremitting global warming.