bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ligand modulation of allosteric networks in an ancestral steroid receptor
Authors: Okafor C. Denise , Ortlund Eric A. 
Published: September 2018

AbstractUnderstanding the evolution of binding specificity, a heavily studied area of research, is key for determining how protein sequence changes alter function. Ligand-activation in the steroid receptor subfamily of transcription factors operates via a common allosteric mechanism which permits extant receptors to respond specifically to their cognate hormones. Here, we combine atomistic simulations with graph theory-based modeling of the inter-residue interactions within protein complexes to gain insight into how allostery drove selectivity in an ancestral receptor. An inactive ligand complex displays weakened allosteric communication, as quantified by suboptimal paths linking two functional surfaces. When function-switching mutations are incorporated, responses in allosteric networks are consistent with ligand activation status. Further analysis reveals residues that modulate features distinguishing active and inactive complexes, identifying a key, conserved residue that is crucial for activation in steroid receptors. We have identified a computational method using dynamic network analysis to probe the allosteric mechanisms driving the evolution of ligand specificity in hormone receptors, determining how residue substitutions altered allosteric networks to permit gain or loss of ligand response. These results may have general utility in elucidating how modern steroid receptors are activated by endogenous and xenobiotic molecules.Author summaryProteins interact with a host of biological partners to mediate their function. These binding partners are able to alter structural properties of the protein to send signals dictating downstream biological activity. This mode of regulation is described as allostery. Here, we perform a computational investigation of allostery in steroid receptors, a family of proteins that regulate a host of important biological processes in response to binding and activation by a steroidal ligand. We leverage a defined evolutionary system where known historical amino acid substitutions within the receptor drive a switch in ligand preference and receptor activation. We show that activating ligands induce stronger allosteric signaling between the ligand and the functional surface on the receptor. In addition, we incorporate evolutionary mutations that are known to alter ligand preference and show that this effect may be explained by allostery. This work provides insight into how amino acid substitutions over evolution affect allostery in proteins, permitting the loss and gain of function.
ATM is activated by ATP depletion and modulates mitochondrial function through NRF1
Authors: Chow Hei-Man , Cheng Aifang , Song Xuan , Swerdel Mavis R. , Hart Ronald P. , Herrup Karl 
Published: September 2018

AbstractWe have uncovered new insights into the symptoms of ataxia-telangiectasia (A-T). Neurons with high physiological activity, particularly cerebellar Purkinje cells, have large and dynamic ATP demands. Depletion of ATP generates reactive oxygen species that activate ATM (the A-T Mutated gene product). Activated in this way, but not by DNA damage, ATM phosphorylates nuclear respiratory factor-1 (NRF1). This leads to NRF1 dimerization, nuclear translocation and the upregulation of nuclear-encoded mitochondrial genes, thus enhancing the capacity of the electron transport chain (ETC) and restoring mitochondrial function. In cells with ATM deficiency, resting ATP levels are normal, but cells replenish ATP poorly following surges in energy demand and chronic ATP insufficiency endangers cell survival. This is a particular problem for energy-intensive cells such as Purkinje cells, which degenerate in A-T. Our findings thus identify ATM as a guardian of mitochondrial output as well as genomic integrity, and suggest that alternate fuel sources may ameliorate A-T disease symptoms.SummaryOxidative stress, resulting from neuronal activity and depleted ATP levels, activates ATM, which phosphorylates NRF1, causing nuclear translocation and upregulation of mitochondrial gene expression. In ATM deficiency, ATP levels recover more slowly, particularly in active neurons with high energy demands.
Axonal tree morphology and signal propagation dynamics improve interneuron classification
Authors: Ofer Netanel , Shefi Orit , Yaari Gur 
Published: September 2018

AbstractNeurons are diverse and can be differentiated by their morphological, electrophysiological, and molecular properties. Current morphology-based classification approaches largely rely on the dendritic tree structure or on the overall axonal projection layout. Here, we use data from public databases of neuronal reconstructions and membrane properties to study the characteristics of the axonal and dendritic trees for interneuron classification. We show that combining signal propagation patterns observed by biophysical simulations of the activity along ramified axonal trees with morphological parameters of the axonal and dendritic trees, significantly improve classification results compared to previous approaches. The classification schemes introduced here can be utilized to robustly classify neuronal subtypes in a functionally relevant manner. Our work paves the way for understanding and utilizing form-function principles in realistic neuronal reconstructions.
Precursor microRNA Identification Using Deep Convolutional Neural Networks
Authors: Do Binh Thanh , Golkov Vladimir , Gürel Göktuğ Erce , Cremers Daniel 
Published: September 2018

AbstractPrecursor microRNA (pre-miRNA) identification is the basis for identifying microRNAs (miRNAs), which have important roles in post-transcriptional regulation of gene expression. In this paper, we propose a deep learning method to identify whether a small non-coding RNA sequence is a pre-miRNA or not. We outperform state-of-the-art methods on three benchmark datasets, namely the human, cross-species, and new datasets. The key of our method is to use a matrix representation of predicted secondary structure as input to a 2D convolutional network. The neural network extracts optimized features automatically instead of using a large number of handcrafted features as most existing methods do. Code and results are available at https://github.com/peace195/miRNA-identification-conv2D.
A model of an e-customized co-design system on garment design
Authors: Li Pei , Chen Jian-Hui 
Published: September 2018

Purpose
To improve the apparel e-customized system and meet consumers’ personalized requirement in the e-customization, the purpose of this paper is to develop an e-customized co-design system on garment design (ECS-GD) that enables users to co-design garment and communicate with stakeholders.

Design/methodology/approach
The e-customized co-design system mainly consists of function and modular structure, communication and evaluation modular. Based on the evolutionary algorithm and fuzzy theory, the e-customized system model is proposed with a presentation of garment interface. Based on the parameters of skirts, technical sketches, fabrics, color, patterns, comments and scores, the decision is made by consumers.

Findings
For the system to be effective, the system was conducted by multi-individuals co-work (consumers, designers, manufacturers and experts). The data flow was congruent to the design knowledge. The expert evaluation and communication were involved in the proposed system.

Research limitations/implications
The limitation of this study is that the system is not tested in experiments. The model, main function and data flow are proposed in this study, which is important in the e-customized co-design system development.

Originality/value
Compared to the e-shopping and garment recommendation, the proposed ECS-GD is a good approach to improve the existing e-customized system and a well solution to help consumers with design knowledge recommending, professional suggestions and evaluations. Besides, the sketches and knowledge recommendation are provided to consumers which is a learning process.
Higher education: exploring productivity over time
Authors: Miles Patti Collett , Peterson Michael , Miles Grant , Bement Danuse 
Published: September 2018

Purpose
Higher education plays a critical role in the health of the US national economy. At the same time, there are increasing concerns regarding the cost of higher education and the effectiveness with which universities are using their money. Accordingly, the purpose of this paper is to examine changes in higher education productivity over the past 15 years across a sample of more than 500 public universities spanning multiple Carnegie classifications. By utilizing measures generated by a commission of the National Education Council, however, attention is more finely focused on the specific costs and outputs related to instructional activity than previous studies.

Design/methodology/approach
This research utilizes the recommendations of the National Education Center committee to examine productivity changes in higher education over the past 14 years. To that end, the hypotheses put forth in this research utilize 15 years data of Institutional Primary Education Data, 549 institutions and 3 productivity measures to assess how productivity in higher education has changed between 2002 and 2015.

Findings
The results of the present research suggest that instructional activity (measured as multifactor productivity) has increased in all Carnegie classifications between 2002 and 2016.

Research limitations/implications
The present study, organized by Carnegie classification, does not specify the cost of increased instructional productivity. As noted, there are concerns regarding whether at least some of the choices a university might make to increase instructional productivity – such as increased class size and/or an increased use of non-tenure track faculty – could adversely influence the quality of instruction and/or diminish student learning. Further, this research does not examine the relationship between research productivity and increasing instructional productivity.

Practical implications
The present study does not address the bigger question of whether the increasing costs of higher education are justified, because universities produce much more than student credit hours. While, in an ideal world, these various outputs will complement one another and utilize at least some of the same resources, each has its own unique inputs and associated expenses. Given this, an overall assessment of the value or productivity of a university as a whole is a very difficult thing to determine and is well beyond the scope of a single study.

Social implications
The present study explicitly focuses on the instructional component of universities and relationship between output and inputs. Ultimately, providing a clearer picture of how instructional productivity in higher education has been increasing over the past 14 years.

Originality/value
This research is the only research of its kind to the best knowledge of the researchers.
Leadership as a driver of entrepreneurship: an international exploratory study
Authors: Felix Claudia , Aparicio Sebastian , Urbano David 
Published: September 2018

PurposeThe purpose of this paper is to examine the influence of cultural leadership factors (charismatic/value-based, team oriented, participative, humane, autonomous and self-protective) on the rates of opportunity and necessity entrepreneurship.Design/methodology/approachThe study integrates insights from institutional and cultural leadership theories to provide a fresh perspective to advance comparative entrepreneurship research. To test the hypotheses, the authors conduct a multiple regression analysis with observations from 34 countries, using data (from the year 2013) from the Global Entrepreneurship Monitor for the dependent variable and from Global Leadership and Organizational Behavior Effectiveness to create leadership factors as independent variables.FindingsThe results show that all the types of leadership considered in the study have a relevant effect on entrepreneurial activity. However, charismatic leadership has a greater effect on entrepreneurial activity, particularly on opportunity entrepreneurship. The research also shows that autonomous leadership has a negative impact on entrepreneurial activity, although, when it is moderated by the humane dimension, this relationship changes.Practical implicationsSince the alternative dimensions facilitate or inhibit the generation of new firm creation, it is critical for researchers, teachers and leaders to learn about and to foster such leadership types.Originality/valueThis research covers a gap in the cross-cultural evidence presented in the literature and suggests the integration of the concepts leadership and entrepreneurship.
Product recalls, lobbying, and firm value
Authors: Rayfield Blake , Unsal Omer 
Published: September 2018

Purpose
The purpose of this paper is to use a unique, hand-collected data set of Food and Drug Administration (FDA)-approved products to understand the effect of lobbying on the product market. The authors gather total 86,462 FDA labels including drug patents, drugs, pre-market approvals and medical devices and test the relationship between lobbying and future firms’ product submissions.

Design/methodology/approach
Using a sample of 86,462 FDA labels including drug patents, drugs, pre-market approvals and medical devices, the authors test the effect of lobbying on a firm’s future product submissions using survival analysis, logit, difference-in-differences and propensity score matching techniques.

Findings
The authors find lobbying firms experience an increase in the number of medical products approved. However, increased number of FDA labeling comes at the cost of product failure. The authors document that lobbying increases product recalls when responsible firms are associated with higher market withdrawals.

Originality/value
This study contributes to both the management literature on corporate lobbying and product recalls. Additionally, the study reveals the connection between pharmaceutical lobbying and firm value.
Managing open innovation
Authors: Naqshbandi M. Muzamil , Tabche Ibrahim , Choudhary Neetu 
Published: September 2018

PurposeThe purpose of this paper is to examine the relationships between empowering leadership style and two types of open innovation: inbound and outbound. The intervening mechanism of employee involvement climate in these relationships is also investigated.Design/methodology/approachThe paper uses data collected using a questionnaire survey from middle and top managers working in various firms in northern India.FindingsResults reveal that empowering leadership positively affects both types of open innovation. Thus empowering leadership supports followers to seek, integrate and diffuse new ideas and knowledge to improve open innovation outcomes. Further, the mediating role of employee involvement climate is established for empowering leadership-inbound open innovation link. This suggests that an empowering leadership style creates an employee involvement climate that empowers employees and involves them in relevant decision-making which consequently enhances a firms inbound open innovation performance.Research limitations/implicationsThis study used a cross-sectional research design and a relatively small sample size. These limitations can affect generalizability of the findings.Originality/valueThe paper contributes to leadership and open innovation literatures and provides insights into how the practitioners can use an appropriate leadership style to maximize success in the open innovation paradigm. The study is one of the first to empirically shed light on this strand of open innovation research.
A building’s design quality: measuring the esoteric
Authors: Zemke Dina Marie , Zhong Yun Ying , Raab Carola 
Published: September 2018

Purpose
Firms that serve customers in the service environment rely on a well-designed servicescape. This is particularly true in the hotel industry, where the hotel’s design is an important part of the product mix. However, despite design’s importance, there is no common instrument available to measure hotel design quality. The purpose of this paper is to present a quantitative method, the Design Quality Indicator, to measure guests’ evaluations of hotel design quality.

Design/methodology/approach
Nearly 5,000 guests of two full-service hotel brands were surveyed soon after a hotel stay (within two weeks of check-out). The DQI’s factor structure is tested using principle components analysis and confirmatory factor analysis to improve the reliability, validity and parsimony of the instrument.

Findings
The study yields a DQI instrument that is reduced from 92 to 41 measurement items, with good reliability and validity, enabling more efficient data collection and analysis.

Research limitations/implications
This study only examines guests’ assessments of two full-service hotel brands. The instrument can be used to explore design’s relationship with numerous outcome variables, such as satisfaction, loyalty, and repatronage intentions, as well as property performance outcomes.

Practical implications
The methods demonstrated can be used by hotel owners and operators to inform resource allocation decisions, particularly when planning for renovations.

Originality/value
This study provides a reliable, validated quantitative assessment of hotel design quality. It is also one of the few studies that elicits feedback about a guest’s actual hotel stay, rather than a hypothesized or simulated stay.
Design and 3D printing customized guides for orthopaedic surgery – lessons learned
Authors: Popescu Diana , Laptoiu Dan , Marinescu Rodica , Botezatu Iozefina 
Published: September 2018

PurposeThis paper aims to fill a research gap by presenting design and 3D printing guidelines and considerations which apply to the development process of patient-specific osteotomy guides for orthopaedic surgery.Design/methodology/approachAnalysis of specific constraints related to patient-specific surgical guides design and 3D printing, lessons learned during the development process of osteotomy guides for orthopaedic surgery, literature review of recent studies in the field and data gathered from questioning a group of surgeons for capturing their preferences in terms of surgical guides design corresponding to precise functionality (materializing cutting trajectories, ensuring unique positioning and stable fixation during surgery), were all used to extract design recommendations.FindingsGeneral design rules for patient-specific osteotomy guides were inferred from examining each step of the design process applied in several case studies in relation to how these guides should be designed to fulfill medical and manufacturing (fused deposition modelling process) constraints. Literature was also investigated for finding other information than the simple reference that the surgical guide is modelled as negative of the bone. It was noticed that literature is focussed more on presenting and discussing medical issues and on assessing surgical outcomes, but hardly at all on guides’ design and design for additive manufacturing aspects. Moreover, surgeons’ opinion was investigated to collect data on different design aspects, as well as interest and willingness to use such 3D-printed surgical guides in training and surgery.Practical implicationsThe study contains useful rules and recommendations for engineers involved in designing and 3D printing patient-specific osteotomy guides.Originality/valueA synergetic approach to identify general rules and recommendations for the patient-specific surgical guides design is presented. Specific constraints are identified and analysed using three case studies of wrist, femur and foot osteotomies. Recent literature is reviewed and surgeons’ opinion is investigated.
Pseudovascular squamous cell carcinoma: A review of the published work and reassessment of prognosis
Authors: Kiyohara Takahiro , Miyamoto Mari , Shijimaya Takako , Nagano Naoko , Nakamaru Sei , Makimura Kaoru , Tanimura Hirotsugu 
Published: September 2018

AbstractA 90‐year‐old Japanese woman presented with a dome‐shaped, dark‐red, ulcerated nodule measuring 23 mm × 19 mm × 9 mm on the right side of the nasal root. Histologically, anastomosing cord‐like arrays of atypical polygonal keratinocytes exhibiting internal pseudolumina containing detached cells and erythrocytes were observed. Although acantholytic and cohesive areas overlapped, cancer pearls were not detected. The lower epidermis partially demonstrated scattered dyskeratotic and acantholytic keratinocytes with loss of polarity, continuous with an underlying tumor mass. The tumor cells were positive for a variety of cytokeratins, p40 and vimentin. The Ki‐67 proliferation index was 50–60%. Both CD31 and CD34 were expressed in reactive blood vessels of the tumor. A local excision margined by 1 mm was performed, followed by X rays and electron beam irradiation. Neither lymph node nor distant metastasis has appeared over the 14 months since the excision. We performed a review of the published work and identified 24 previously reported patients with pseudovascular squamous cell carcinoma of the skin, oral mucosa and vulva to reassess the prognosis of this tumor. In 12 of these patients (50%), sites other than the head and neck were involved. Eight (33%) tumor‐associated deaths occurred. It is believed that pseudovascular squamous cell carcinoma has a tendency to develop at morbid skin and mucous membranes sites in organs other than the face and neck and to possess an aggressive clinical behavior.
Predation risk for reptiles is highest at remnant edges in agricultural landscapes
Authors: Hansen Nicole A. , Sato Chloe F. , Michael Damian R. , Lindenmayer David B. , Driscoll Don A. 
Published: September 2018

Abstract

Preventing biodiversity loss in fragmented agricultural landscapes is a global problem. The persistence of biodiversity within remnant vegetation can be influenced by an animal's ability to move through the farmland matrix between habitat patches. Yet, many of the mechanisms driving species occurrence within these landscapes are poorly understood, particularly for reptiles.

We used scented and unscented plasticine lizard models and wildlife cameras to (a) estimate predation risk of reptiles in four farmland types (crop field, pasture paddock, restoration tree planting and areas with applied woody mulch) relative to the patch edge and remnant vegetation, and (b) examine how predation risk was influenced by temporal change in the matrix (crop harvesting).

Birds (55.1%), mammals (41.1%), reptiles (3.4%), and invertebrates (0.5%) attacked models, of which 87% were native species. Mammalian predators were 60.2% more likely to attack scented models then unscented models. Bird predators were not influenced by scent.

We found predator attacks on models were highest at edges (49%, irrespective of adjacent farmland type, with a reduced risk within farmland (29%) and remnant patches (33%) (p < 0.01). Both mammal and bird predators contributed to high numbers of predation attempts at edges.

Removal of crops did not increase predation attempts in crop fields or other farmland types, although predation attempts were significantly lower along the crop transect after harvesting, compared to the woody debris transect. However, numbers of predation attempts were higher in edge habitats, particularly prior to harvesting.

Synthesis and applications. Reptiles are at risk of predation by birds and mammals in both remnant patches and the farmland matrix, particularly in edge habitat. Our results demonstrate that edge habitats are potentially riskier for lizards than the farmland. Vulnerability to predation may be increased by a lack of shelter within edge habitats such as by increasing visibility of reptiles to predators. Therefore, to benefit reptiles, land managers could provide shelter (rocks, logs, and grasses), particularly between remnants and linear plantings which could improve landscape connectivity.