bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computer-guided Binding Mode Identification and Affinity Improvement of an LRR Protein Binder without Structure Determination
Authors: Choi Yoonjoo , Jeong Sukyo , Choi Jung-Min , Ndong Christian , Bailey-Kellogg Chris , Griswold Karl E. , Kim Hak-Sung 
Published: December 2019

AbstractPrecise binding mode identification and subsequent affinity improvement without structure determination remain a challenge in the development of therapeutic proteins. However, relevant experimental techniques are generally quite costly, and purely computational methods have been unreliable. Here, we show that integrated computational and experimental epitope localization followed by full-atom energy minimization can yield an accurate complex model structure which ultimately enables effective affinity improvement and redesign of binding specificity. As proof-of-concept, we used a leucine-rich repeat (LRR) protein binder, called a repebody (Rb), that specifically recognizes human IgG1(hIgG1). We performed computationally-guided identification of the Rb:hIgG1binding mode and leveraged the resulting model to reengineer the Rb so as to significantly increase its binding affinity for hIgG1as well as redesign its specificity toward multiple IgGs from other species. Experimental structure determination verified that our Rb:hIgG1model closely matched the co-crystal structure. Using a benchmark of other LRR protein complexes, we further demonstrated that the present approach may be broadly applicable to proteins undergoing relatively small conformational changes upon target binding.Author SummaryIt is quite challenging for computational methods to determine how proteins interact and to design mutations to alter their binding affinity and specificity. Despite recent advances in computational methods, however,in silicoevaluation of binding energies has proven to be extremely difficult. We show that, in the case of protein-protein interactions where only small structural changes occur upon target binding, an integrated computational and experimental approach can identify a binding mode and drive reengineering efforts to improve binding affinity or specificity. Using as a model system a leucine-rich repeat (LRR) protein binder that recognizes human IgG1, our approach yielded a model of the protein complex that was very similar to the subsequently experimentally determined co-crystal structure, and enabled design of variants with significantly improved IgG1binding affinity and with the ability to recognize IgG1from other species.
Frequency- and state-dependent effects of hippocampal neural disinhibition on hippocampal local field potential oscillations in anaesthetised rats
Authors: Gwilt Miriam , Bauer Markus , Bast Tobias 
Published: December 2019

AbstractReduced inhibitory GABA function, so-called neural disinhibition, has been implicated in cognitive disorders, including schizophrenia and age-related cognitive decline. We previously showed in rats that hippocampal disinhibition by local microinfusion of the GABA-A antagonist picrotoxin disrupted memory and attention and enhanced hippocampal multi-unit burst firing recorded around the infusion site under isoflurane anaesthesia. Here, we analysed the hippocampal LFP recorded alongside the multi-unit data. We predicted frequency-specific LFP changes, based on previous studies implicating GABA in hippocampal oscillations, with the weight of evidence suggesting that disinhibition would facilitate theta and disrupt gamma oscillations. Using a new semi-automated method based on the kurtosis of the LFP peak-amplitude distribution as well as on amplitude envelope thresholding, we separated three distinct hippocampal LFP states under isoflurane anaesthesia: ‘burst’ and ‘suppression’ states – high-amplitude LFP-spike bursts and the interspersed low-amplitude periods – and a medium-amplitude ‘continuous’ state. The burst state showed greater overall power than suppression and continuous states and higher relative delta/theta power, but lower relative beta/gamma power. The burst state also showed reduced functional connectivity across the hippocampal recording area, especially around theta and beta frequencies. Overall neuronal firing was higher in the burst than the other two states, whereas the proportion of burst firing was higher in burst and continuous states than the suppression state. Disinhibition caused state- and frequency-dependent LFP changes, tending to increase power at lower frequencies (<20Hz), but to decrease power and connectivity at higher frequencies (>20Hz) in burst and suppression states. The disinhibition-induced enhancement of multi-unit bursting was also state-dependent, tending to be more pronounced in burst and suppression states than the continuous state. Overall, we characterized three distinct hippocampal LFP states in isoflurane-anaesthetized rats. Disinhibition changed hippocampal LFP oscillations in a state- and frequency-dependent way. Moreover, the disinhibition-induced enhancement of multi-unit bursting was also LFP-state dependent.
Cellular state determines the multimodal signaling response of single cells
Authors: Kramer Bernhard A. , Pelkmans Lucas 
Published: December 2019

AbstractNumerous fundamental biological processes require individual cells to correctly interpret and accurately respond to incoming cues. How intracellular signaling networks achieve the integration of complex information from various contexts remains unclear. Here we quantify epidermal growth factor-induced heterogeneous activation of multiple signaling proteins, as well as cellular state markers, in the same single cells across multiple spatial scales. We find that the acute response of each node in a signaling network is tightly coupled to the cellular state in a partially non-redundant manner. This generates a multimodal response that senses the diversity of cellular states better than any individual response alone and allows individual cells to accurately place growth factor concentration in the context of their cellular state. We propose that the non-redundant multimodal property of signaling networks in mammalian cells underlies specific and context-aware cellular decision making in a multicellular setting.
Scavenging dicarbonyls with 5’-O-pentyl-pyridoxamine increases HDL net cholesterol efflux capacity and attenuates atherosclerosis and insulin resistance
Authors: Huang Jiansheng , Tao Huan , Yancey Patricia G. , Leuthner Zoe , May-Zhang Linda S. , Jung Ju-Yang , Zhang Youmin , Ding Lei , Amarnath Venkataraman , Liu Dianxin , Collins Sheila , Davies Sean S. , Linton MacRae F. 
Published: December 2019

AbstractObjectiveOxidative stress contributes to the development of insulin resistance (IR) and atherosclerosis. Peroxidation of lipids produces reactive dicarbonyls such as Isolevuglandins (IsoLG) and malondialdehyde (MDA) that covalently bind plasma/cellular proteins, phospholipids, and DNA leading to altered function and toxicity. We examined whether scavenging reactive dicarbonyls with 5’-O-pentyl-pyridoxamine (PPM) protects against the development of IR and atherosclerosis inLdlr-/-mice.MethodsMale or femaleLdlr-/-mice were fed a western diet (WD) for 16 weeks and treated with PPM versus vehicle alone. Plaque extent, dicarbonyl-lysyl adducts, efferocytosis, apoptosis, macrophage inflammation, and necrotic area were measured. Plasma MDA-LDL adducts and the in vivo and in vitro effects of PPM on the ability of HDL to reduce macrophage cholesterol were measured. Blood Ly6Chimonocytes and ex vivo 5-ethynyl-2’-deoxyuridine (EdU) incorporation into bone marrow CD11b+ monocytes and CD34+ hematopoietic stem and progenitor cells (HSPC) were also examined. IR was examined by measuring fasting glucose/insulin levels and tolerance to insulin/glucose challenge.ResultsPPM reduced the proximal aortic atherosclerosis by 48% and by 46% in female and maleLdlr-/-mice, respectively. PPM also decreased IR and hepatic fat and inflammation in maleLdlr-/-mice. Importantly, PPM decreased plasma MDA-LDL adducts and prevented the accumulation of plaque MDA- and IsoLG-lysyl adducts inLdlr-/-mice. In addition, PPM increased the net cholesterol efflux capacity of HDL fromLdlr-/-mice and prevented both the in vitro impairment of HDL net cholesterol efflux capacity and apoAI crosslinking by MPO generated hypochlorous acid. Moreover, PPM decreased features of plaque instability including decreased proinflammatory M1-like macrophages, IL-1β expression, myeloperoxidase, apoptosis, and necrotic core. In contrast, PPM increased M2-like macrophages, Tregs, fibrous cap thickness, and efferocytosis. Furthermore, PPM reduced inflammatory monocytosis as evidenced by decreased blood Ly6Chimonocytes and proliferation of bone marrow monocytes and HSPC fromLdlr-/-mice.ConclusionsPPM has pleotropic atheroprotective effects in a murine model of familial hypercholesterolemia, supporting the therapeutic potential of reactive dicarbonyl scavenging in the treatment of IR and atherosclerotic cardiovascular disease.
Does previous work experience matter in students’ learning in higher project management education?
Authors: Sharma Keshav Kumar , Israel D. , Bhalla Bhavna 
Published: December 2019

PurposeIn view of the substantial gaps between desirable and actual competencies of project practitioners, there is a genuine and continual need to improve approaches towards project management education. The purpose of this paper is to empirically examine whether previous work experience of students pursuing a master’s programme in project management plays a role in their understanding and learning from the programme.Design/methodology/approachSurvey data were collected from 282 respondents, who included working project professionals along with first-year (junior) and second-year (senior) students of a two-year postgraduate programme in project management. Considering the responses of working project professionals as the benchmark, the paper employs exploratory factor analysis and multiple comparisons to examine differences in the perceived importance given to factor groupings of critical success factors (CSFs) of construction projects by different respondent groups.FindingsResults of the study suggest that irrespective of students’ seniority in the postgraduate programme, responses of students with previous project work experience more closely match the responses of project professionals, in contrast to students without such experience. The results indicate that students’ previous project work experience does play a role in their understanding and learning. In addition, the paper also identifies four factor groupings of CSFs and, diverging from past studies, conceptualises “alignment” as a new factor grouping.Practical implicationsFindings support the view that adequate previous work experience may be included as an essential qualifying requirement for pursuing higher education in project management.Originality/valueTo the best of the authors’ knowledge, this is one of the first empirical studies that investigate the requirement of students’ previous work experience and reveals its significance in higher project management education.
Determining the level of development for BIM implementation in large-scale projects
Authors: Alshorafa Raif , Ergen Esin 
Published: December 2019

Purpose
Proper definition of level of development (LOD) is one of the significant issues in building information modeling (BIM) applications; however, it is still not adequately addressed during BIM implementations. The purpose of this paper is to investigate and describe the current practice in defining the LOD in large-scale BIM-based projects and identify the challenges and solutions that were provided.

Design/methodology/approach
Four case studies were performed at four different types of large-scale projects to depict the current practice in determining the LOD and the required properties of elements that are going to be included in a BIM model. Semi-structured face-to-face interviews were performed to collect information from six professionals from four international firms.

Findings
The findings of the case studies revealed that defining LOD is an ambiguous process and requires high-cumulated experience. The results provide the challenges, adopted solutions and lessons learned. It was highlighted that the cost of including an element or related information in the model should be compared to the benefit of having that information in the model from the perspective of defined BIM uses.

Research limitations/implications
The findings are based on the projects that were performed in three developing countries. However, the main contractors were international companies and the construction management firms were well-known companies in the USA. In the future, additional case studies can be performed in other countries to identify similarities and regional differences.

Practical implications
The results of this study can be used to highlight the current needs in determining the LOD and guide the efforts for developing standards and policies in the AEC sector to streamline BIM adoption process in practice. The practitioners can utilize the findings of this study to increase their efficiency in adopting BIM and to decrease the time loss and cost overruns.

Originality/value
Most of the previous studies investigated the benefits and challenges when adopting BIM, and few of them considered LOD definition as a core part of this process. This study specifically investigated the current practice in determining the LOD and the required properties of elements that are going to be included in a BIM model. It also described the applied solutions and lessons learned in the case studies.
Is there a Ramadhan effect on Sharia mutual funds? Evidence from Indonesia and Malaysia
Authors: Rokhim Rofikoh , Octaviani Irma 
Published: December 2019

Purpose
This paper aims to examine whether Sharia mutual fund managers are able to gain abnormal returns from what is called the Ramadhan effect.

Design/methodology/approach
The authors use GARCH regression on daily data of domestic Sharia mutual fund performance in Indonesia and Malaysia over the period of 2007-2017.

Findings
The authors find that the Ramadhan effect is not a strong predictor of Sharia fund excess return in Indonesia and Malaysia, and they identify a positive Ramadhan abnormal return on the Malaysia Sharia Equity Fund. This result shows there is size effect on sharia fund excess return in Indonesia and value effect on Sharia Balanced Fund in both markets. It is suggested that the effect of market excess return in Indonesia is stronger than in Malaysia.

Research limitations/implications
The samples are limited to Sharia Funds over the period 2007-2017.

Practical implications
The authors suggest that size and value effect could be considered to develop the selection and timing strategies to explore the Ramadhan effect.

Originality/value
This study focuses on Indonesia and Malaysia, the two largest Islamic Stock Markets in Southeast Asia and examines specific on Sharia Mutual Fund (equity and balanced fund). It also compares differences in total performance measures between the Ramadhan period and non-Ramadhan period.
Mapping literacies
Authors: Zimmerman Margaret S. 
Published: December 2019

Purpose
Information literacy and health literacy skills are positively correlated with indicators of quality of life. Assessing these literacies, however, can be daunting – particularly with people that may not respond well to prose-based tools. The purpose of this paper is to use information horizons methodology as a metric that may be reflective of literacies.

Design/methodology/approach
Following a power analysis to insure statistical significance, a sample of 161 participants was recruited from a university population and given formal, vetted measures of information literacy and health literacy and then was asked to create an information horizons map within a health-related context. The information horizons maps were evaluated in two different ways. First, the number of sources was counted. Then, the quality of sources was factored in. Multiple regression analysis was applied to both metrics as independent variables with the other assessments as dependent variables. Anker, Reinhart, and Feeley’s model provided the conceptual framework for the study.

Findings
Information horizons mapping was not found to have a significant relationship with measures of information literacy. However, there were strong, statistically significant relationships with the measures of health literacy employed in this study.

Originality/value
Employing information horizons methodology as a means of providing a metric to assess literacies may be helpful in providing a more complete picture of a person’s abilities. While the current assessment tools have value, this method has the potential to provide important information about the health literacy of people who are not traditionally well represented by prose-based measures.
Examining the relationship between the price, the characteristics and the visitor evaluation of attributes of Italian farmhouses with an educational farm
Authors: Fanelli Rosa Maria 
Published: December 2019

PurposeThe purpose of this paper is to examine the relationship between the price charged for a guest room in a farmhouse with an educational farm, the farmhouse characteristics and the visitor evaluation of the principal external and internal farmhouse attributes.Design/methodology/approachA large sample of 10,880 visitor reviews, extrapolated from the websites of 399 Italian farmhouses with an educational farm (FEF), was analyzed. Principal component analysis (PCA) was performed to identify the main latent dimensions of the farmhouses (visitor satisfaction with farmhouse attributes, farmhouse dimensions, visitor frequency, farmhouse services, types of accommodation and altitude) that affect the price charged for a guest room. Subsequently, multivariate regression was applied to measure the impact of these new latent factors on the price.FindingsOverall, the results indicate that the price of a farmhouse with an educational farm – in the context of this niche of the Italian agritourism sector – reflects the visitor evaluation of the farmhouse attributes (especially activities and facilities available in the surrounding countryside), the farmhouse dimensions, the types of accommodation, the number of services on offer and the presence of connectivity (WI-FI). In addition, the results reveal that the price represents an important driver that guides guests in their choice of a farmhouse and that it affects visitor satisfaction with farmhouse attributes.Research limitations/implicationsBecause of the sample chosen, the data gathered are limited to one type of organization – Italian FEF. Furthermore, it may be important to investigate in more depth some issues that remain partly unanswered that concern this niche of the Italian agritourism sector.Practical implicationsThanks to the identification of latent dimensions by PCA and the examination of their impact on the farmhouse price, farmhouse operators can understanda priorithe main determinants on which to focus to improve the quality of activities and facilities available in the farmhouse location to better satisfy visitor expectations.Originality/valueThis study provides new and practical insights into the farmhouse experience in Italian municipalities, an area where very limited research has been conducted. Indeed, this is one of the few studies to focus on online reviews to evaluate more than two farmhouse attributes and their impact on pricing.
Separation of multi‐mode surface waves by supervised machine learning methods
Authors: Li Jing , Chen Yuqing , Schuster Gerard T. 
Published: December 2019

ABSTRACTLogistic regression, neural networks and support vector machines are tested for their effectiveness in isolating surface waves in seismic shot records. To distinguish surface waves from other arrivals, we train the algorithms on three distinguishing features of surface‐wave dispersion curves in the domain: spectrum coherency of the trace's magnitude spectrum, local dip and the frequency range for a fixed wavenumber k in the spectrum. Numerical tests on synthetic data show that the kernel‐based support vector machines algorithm gives the highest accuracy in predicting the surface‐wave window in the domain compared to neural networks and logistic regression. This window is also used to automatically pick the fundamental dispersion curve. The other two methods correctly pick the low‐frequency part of the dispersion curve but fail at higher frequencies where there is interference with higher‐order modes.
Habitat predicts local prevalence of migratory behaviour in an alpine ungulate
Authors: Spitz Derek B. , Hebblewhite Mark , Stephenson Thomas R. 
Published: December 2019

Abstract

The resource hierarchy hypothesis predicts that the most important factors limiting a species’ distribution act at the coarsest spatial scales. However, resource selection behaviour affords mobile organisms the opportunity to adopt a range of tactics for navigating spatial trade‐offs between competing biotic and abiotic constraints. Throughout the animal kingdom, partial migration (where some individuals migrate, and others remain resident year round) offers a pervasive example of such behavioural polymorphism. Identifying the differences between these behaviours is therefore central to understanding the conditions (habitat) needed to sustain migrant and resident populations.

Here we test an extension of the resource hierarchy hypothesis. We hypothesized that rather than responding to a single limiting factor, migration and residency represent contrasting scale‐specific approaches to managing trade‐offs between forage, predation risk and severe winter conditions. Furthermore, we predicted that the distribution of habitat selected by migrants and residents is predictive of the local prevalence of migratory behaviour.

To test these hypotheses, we quantified migratory status‐ (resident/migrant) and season‐specific (winter/summer) differences in resource selection by eight populations of federally endangered Sierra Nevada bighorn sheep Ovis canadensis sierrae across three spatial scales: population range, individual range and within individual range. We then integrated these spatial predictions to produce separate spatial predictions of migrant and resident winter habitat.

As predicted, model selection provided strong evidence for the importance of status‐specific differences in resource selection. Residents showed stronger coarse‐scale selection for terrain associated with predator avoidance and stronger fine‐scale selection for greenness, while in migrants this pattern was reversed. Availability of migrant habitat predicted the local prevalence of migration (top model pseudo R2 of .87).

Our ability to respond to global declines of migratory species depends on improving our understanding of the conditions required to maintain migratory behaviour. Through explicitly contrasting migrant and resident behaviour, our results illustrate seasonal differences in migrant and resident habitat and how these two behaviours represent responses to different limiting conditions. Our analyses provides a novel empirical basis for assessing the local prevalence of migratory behaviour across large landscapes.