bluuebunny/crossref_metadata_2025_split huggingface dataset:
The anti-apoptosis ubiquitin E3 ligase XIAP promotes autophagosome-lysosome fusion during autophagy
Authors: Poetsch Isabella , Ebner Petra , Deszcz Luiza , Bachtrog Iris , Stephani Madlen , Díaz Carlos Gómez , Dagdas Yasin , Ikeda Fumiyo 
Published: March 2018

AbstractThe Inhibitor of Apoptosis Protein (IAP) family members are well-known endogenous regulators of apoptosis. Whether these proteins regulate other degradation pathways is unclear. Here, we discovered that the IAP member X-linked IAP (XIAP) is crucial for macroautophagy. Loss of XIAP in mouse and human cells inhibited starvation-induced degradation of LC3 proteins and an autophagy substrate p62. It also led to the accumulation of mature autophagosomes, suggesting that XIAP controls autophagic flux by mediating autolysosome formation.Xiap∆RING/∆RINGcells phenocopy the autophagy defects ofXiap−/−cells, suggesting that the ubiquitinating activity mediated by the catalytic RING domain is critical for autophagic flux. We found that XIAP physically interacts with Syntaxin 17, a regulator of autophagosome-lysosome fusion. Syntaxin 17-positive mature autophagosomes positive accumulate in the cytoplasm of starvedXiap−/−cells, suggesting that XIAP might regulate its dissociation from autophagosomes after fusion. XIAP selectively interacts with GABARAP among LC3 family members via the LIR-Docking Site (LDS). Together, our data suggest that XIAP-mediated ubiquitination regulates key autophagy regulators to promote autophagosome-lysosome fusion.
Fission yeast NDR/LATS kinase Orb6 regulates exocytosis via phosphorylation of exocyst complex
Authors: Tay Ye Dee , Leda Marcin , Spanos Christos , Rappsilber Juri , Goryachev Andrew B. , Sawin Kenneth E. 
Published: March 2018

ABSTRACTNDR/LATS kinases regulate multiple aspects of cell polarity and morphogenesis from yeast to mammals, but few of their substrates are known. Fission yeast NDR/LATS kinase Orb6 has been proposed to control cell polarity via spatial regulation of Gef1, a guanine nucleotide exchange factor for the small GTPase Cdc42. Here we show that Orb6 plays a critical role as a positive regulator of exocytosis, independent of Gef1. Through Orb6 inhibition in vivo and quantitative global phosphoproteomics, we identify several proteins involved in membrane trafficking as Orb6 targets, and we confirm Sec3 and Sec5, conserved components of the exocyst complex, as substrates of Orb6 both in vivo and in vitro. Our results suggest that Orb6 kinase activity is crucial for exocyst localization to actively-growing cell tips and for exocyst activity during septum dissolution after cytokinesis. We further show that Orb6 phosphorylation of Sec3 serine-201 contributes to exocyst function in parallel with exocyst protein Exo70. We propose that Orb6 contributes to polarized growth by regulating membrane trafficking at multiple levels.
A Patient-Derived Cellular Model for Huntington’s Disease Reveals Phenotypes at Clinically Relevant CAG Lengths
Authors: Hung Claudia Lin-Kar , Maiuri Tamara , Bowie Laura Erin , Gotesman Ryan , Son Susie , Falcone Mina , Giordano James Victor , Mattis Virginia , Lau Trevor , Kwan Vickie , Wheeler Vanessa , Schertzer Jonathan , Singh Karun , Truant Ray 
Published: March 2018

ABSTRACTThe huntingtin protein participates in several cellular processes that are disrupted when the polyglutamine tract is expanded beyond a threshold of 37 CAG DNA repeats in Huntington’s disease (HD). Cellular biology approaches to understand these functional disruptions in HD have primarily focused on cell lines with synthetically long CAG length alleles that clinically represent outliers in this disease and a more severe form of HD that lacks age-onset. Patient-derived fibroblasts are limited to a finite number of passages before succumbing to cellular senescence. We used human telomerase reverse transcriptase (hTERT) to immortalize fibroblasts taken from individuals of varying age, sex, disease onset and CAG repeat length, which we have termed TruHD cells. TruHD cells display classic HD phenotypes of altered morphology, size and growth rate, increased sensitivity to oxidative stress, aberrant ADP/ATP ratios and hypophosphorylated huntingtin protein. We additionally observed dysregulated ROS-dependent huntingtin localization to nuclear speckles in HD cells. We report the generation and characterization of a human, clinically relevant cellular model for investigating disease mechanisms in HD at the single cell level, which, unlike transformed cell lines, maintains TP53 function critical for huntingtin transcriptional regulation and genomic integrity.
Prediction of prostate cancer by deep learning with multilayer artificial neural network
Authors: Takeuchi Takumi , Hattori-Kato Mami , Okuno Yumiko , Iwai Satoshi , Mikami Koji 
Published: March 2018

AbstractObjectivesTo predict the rate of prostate cancer detection on prostate biopsy more accurately, the performance of deep learning utilizing a multilayer artificial neural network was investigated.Materials and methodsA total of 334 patients who underwent multiparametric magnetic resonance imaging before ultrasonography-guided transrectal 12-core prostate biopsy were enrolled in the analysis. Twenty-two non-selected variables as well as selected ones by least absolute shrinkage and selection operator (Lasso) regression analysis and by stepwise logistic regression analysis were input into the constructed multilayer artificial neural network (ANN) programs. 232 patients were used as training cases of ANN programs, and the remaining 102 patients were for the test to output the probability of prostate cancer existence, accuracy of prostate cancer prediction, and area under the receiver operating characteristic (ROC) curve with the learned model.ResultsWith any prostate cancer objective variable, Lasso and stepwise regression analyses selected 12 and 9 explanatory variables from 22, respectively. In common between them, age at biopsy, findings on digital rectal examination, findings in the peripheral zone on MRI diffusion-weighted imaging, and body mass index were positively influential variables, while numbers of previous prostatic biopsy and prostate volume were negatively influential. Using trained ANNs with multiple hidden layers, the accuracy of predicting any prostate cancer in test samples was about 5-10% higher compared with that with logistic regression analysis (LR). The AUCs with multilayer ANN were significantly larger on inputting variables that were selected by the stepwise logistic regression compared with the AUC with LR. The ANN had a higher net-benefit than LR between prostate cancer probability cut-off values of 0.38 and 0.6.ConclusionANN accurately predicted prostate cancer without biopsy marginally better than LR. However, for clinical application, ANN performance may still need improvement.
Gambling-related harms and homelessness: findings from a scoping review
Authors: Bramley Stephanie , Norrie Caroline , Manthorpe Jill 
Published: March 2018

PurposePeople experiencing homelessness are being identified as a potentially vulnerable group in relation to gambling-related harm. The purpose of this paper is to explore the links between gambling-related harm and homelessness.Design/methodology/approachA scoping review of the English-language literature was conducted in 2016-2017 using a wide range of international sources. Qualitative content analysis was employed to code and identify key themes within the literature.FindingsFive themes were identified: emerging knowledge about why people experiencing homelessness may participate in gambling; emerging knowledge about the prevalence of gambling within the homeless population; the likelihood that gambling-related harm is under-reported within the homeless population; emerging knowledge about the extent that people experiencing homelessness access gambling support services; and limited awareness about the potential impact of gambling participation among people experiencing homelessness.Originality/valueThe paper reviews research concerning the links between gambling, gambling-related harm and homelessness, which may be relevant to those working with people experiencing homelessness.
Open kitchen vs closed kitchen
Authors: Byun Jaemun , Jang SooCheong (Shawn) 
Published: March 2018

PurposeThis study aims to investigate, when a service failure occurs, whether circumstantial cues could be used to encourage more positive responses by customers toward restaurants through the mediation of causal attribution.Design/methodology/approachA 2 (cause of service failure: easily observable vs difficult-to-observe) × 2 (kitchen design: open vs closed) between-subject experiment is used to analyze customers’ causal attributions of service failures and resultant responses.FindingsWhen a service failure whose cause is easy to identify occurs, customers at open-kitchen restaurants show more negative responses than those at closed-kitchen restaurants because they are likely to attribute the responsibility to the restaurant. Attribution is confirmed to mediate the relationship between the interaction of service failure by kitchen design and customers’ responses.Practical implicationsDiverse circumstantial cues should be actively used to encourage more positive responses by customers. The mediating role of causal attribution should be considered in managing customers’ responses toward service failures.Originality/valueThis study finds that circumstantial cues could be useful in dealing with service failures in restaurants by confirming the mediating role of causal attribution.
Do loyalty programs really matter for hotel operational and financial performance?
Authors: Hua Nan , Wei Wei , L. DeFranco Agnes , Wang Dan 
Published: March 2018

PurposeThis study aims to use a sample of 2,120 individual hotel properties between 2011 and 2013 to evaluate the impact of loyalty programs on hotel operational and financial performance.Design/methodology/approachThis study provides empirical support for the impact of loyalty program based on both cross-sectional and panel data analyses and uses the instrumental variable technique to avoid potential heteroscedasticity, autocorrelation and simultaneity issues.FindingsFindings of this study show that loyalty program expenses have a significant and positive impact on all three operational performance indicators of RevPAR, ADR and Occupancy and the financial performance indicator of gross operating profit.Research limitations/implicationsThis study suggests that the benefits of loyalty programs should be understood against the backdrop of a reasonable set of controlled variables such as e-commerce, franchise, advertising, other marketing expenses, hotel size and hotel chain scales.Originality/valueGiven the conflicting viewpoints about the positive and negative impacts of loyalty programs, and that the literature is scant on empirical validation of the impact of loyalty programs on the overall operational and financial performance of hotel properties, this study is an early attempt to empirically test the impact of loyalty programs on a number of hotel operational and financial performance indicators by using an extensive list of individual hotel properties between 2011 and 2013.
Motivation exchange rate: the real value of incentives
Authors: Huang Yundong 
Published: March 2018

Purpose
The purpose of this paper is to describe how individuals compare the value of different types of incentive. This is similar to comparison in the financial field for currency exchange. The proposed exchange rate between incentives is referred to here as motivation exchange rate (MER).

Design/methodology/approach
Survey-based empirical data were analyzed to test for the existence of MER, based on 330 samples collected from a number of organizations. Partial least square-based structural equation modeling was applied to test the research model, specifically examining the exchange rate between intrinsic motivation and monetary incentives.

Findings
Individuals place their own value on job enjoyment. The present analysis suggests that MER exists between intrinsic motivation and monetary incentive and varies among individuals.

Originality/value
The motivation literature has shown that individuals have their own preferences for different types of incentives. When studying employees’ working behavior, scholars have traditionally focused on preferred incentives. However, the present study reveals that these predominant incentives may change when employees are sufficiently compensated by other types of incentive; how much is “sufficient” depends on MER, as elaborated here.
Parametric study on load ratio effect on the flexural bending behaviour of axially-restrained HSS steel beams subjected to fire
Authors: Salem Osama (Sam) 
Published: March 2018

Purpose
In fire condition, the limiting temperature of a restrained steel beam depends on a few parameters, e.g. temperature distributions along and across the beam, beam’s load ratio and span length. The purpose of this study is to investigate the structural fire behaviour of axially restrained steel beams under different beam’s load ratios, taking into consideration the effect of the beam’s end connections configuration.

Design/methodology/approach
A three-dimensional finite element (FE) computer model has been developed to simulate the structural fire behaviour of axially restrained steel beams and their end connections. After successfully validating the developed model against the outcomes of the available large-size fire resistance experiments, the FE model has been used in a parametric study to investigate the beam’s load ratio effect on the behaviour of the axially restrained steel beams and their end connections.

Findings
The parametric study showed that increasing the beam loading level significantly increased the beam deflections at elevated temperatures; where, increasing the beam’s load ratio from 0.5 to 0.9 reduced the beam fire resistance by about 100 s. In contrast, decreasing the beam’s load ratio from 0.5 to 0.3 allowed the beam to easily achieve a 30-min fire resistance rating with no fire protection applied.

Originality/value
Experimental parametric studies are difficult to control in a laboratory setting and are also expensive and time consuming. Therefore, the reasonable accuracy of the validated FE model in reproducing the experimental fire behaviour of steel beams and their end connections makes it a very useful tool for both numerical and analytical studies.
Financial restructuring and target capital structure
Authors: Mielcarz Paweł , Osiichuk Dmytro , Owczarkowski Ryszard 
Published: March 2018

Purpose
This paper aims to present an iterative algorithm that yields the amount of debt contracting/repayment or equity investment necessary to achieve the target capital structure. The model also helps to estimate the gains in shareholder value that result from financial restructuring process and lead to the optimal leverage ratio.

Design/methodology/approach
The paper maintains that certain benchmarks – i.e. industry average financial leverage and unlevered beta corrected for cash – make it possible to determine the parameters of the optimal capital structure for the company, so a failure to adjust to the target may result in value destruction.

Findings
The paper presents an iterative algorithm that yields the amount of debt contracting/repayment or equity investment necessary to achieve the target capital structure.

Originality/value
The proposed algorithm overcomes the methodological problems of existing approaches to the estimation of shareholder value gained through financial restructuring and implicitly solves the circularity problem in the calculation of the weighted average cost of capital.
The motivational heterogeneity of an all-equity capital structure
Authors: Caban David 
Published: March 2018

Purpose
This paper aims to investigate whether all-equity firms are a heterogeneous group as it relates to agency costs when compared to a matched sample of levered firms and to contribute toward the understanding of the “low leverage” puzzle and the motivations behind such a perplexing phenomenon.

Design/methodology/approach
Propensity score matching (PSM) is used to control for endogeneity issues common to this line of research. Because all-equity firms are self-selecting, it is not possible to conduct a true randomized study. PSM attempts to simulate a randomized study by selecting matching observations with similar propensity scores as the all-equity observations.

Findings
Agency costs are not the only explanation leading to the implementation of an all-equity capital structure. The motivation of such structure is strongly influenced by free cash flows (FCF) and growth opportunities (GO), whereby firms that have high levels FCF combined with low GO exhibit higher levels of agency costs versus their levered peers, while those that have low levels of FCF and high GO exhibit no significant difference in agency costs.

Practical implications
A better understanding of why a firm chooses such an extreme capital structure can help investors, auditors and potential future creditors in their decision-making process.

Originality/value
Most prior research treats capital structure as an exogenous variable. By applying PSM, not previously used in prior research, a new methodology is used to address the endogeneity issue related to observational studies such as this one. This paper contributes toward further understanding the perplexing “low-leverage” puzzle often discussed in the financial and accounting literature.
How does directors’ remuneration affect SMEs’ performance?
Authors: Afrifa Godfred Adjappong , Adesina Oluseyi Oluseun 
Published: March 2018

PurposeThe purpose of this paper is to empirically explain the relationship between the remuneration levels of a sample of listed small and medium enterprise (SME) directors and firm performance. The paper also investigates whether deviations from the optimal directors’ remuneration level reduces firm performance.Design/methodology/approachThe study uses a panel data regression analysis of 802 AIM-listed SMEs over an eight-year period (2005-2012).FindingsUsing a non-linear approach, the results show that an optimum director’s remuneration level is calculated by comparing the benefits and costs of director’s remuneration. Hence, the paper not only shows how directors’ remuneration level affects firm performance but it also extends the stream of knowledge by indicating how a deviation from the optimal point influences UK-listed SME performances. Moreover, the results show that the effect of directors’ remuneration on firm performance is greater during a financial crisis period.Originality/valueCompared with previous literature on directors’ remuneration, this paper focuses on AIM-listed SMEs, and the author’s finding of a concave relationship between directors’ remuneration level and performance of leads them to recommend that firms, especially SMEs, should endeavour to determine the optimal level of directors’ remuneration to maximise performance.
Doing time on a TC: how effective are drug-free therapeutic communities in prison? A review of the literature
Authors: Aslan Laura 
Published: March 2018

Purpose
Therapeutic communities (TC’s) are consciously designed, living-learning environments designed to evoke social, psychological and behavioural change. The success of the residential TC model saw these community-led, self-help environments for addicts move into custodial settings and early evidence suggests this transition was effective. The purpose of this paper is to examine the evidence relevant to the effectiveness of prison based, drug-free TCs.

Design/methodology/approach
In order to establish their true efficiency, particular focus has been placed on studies conducted over the last ten years (2007-2017).

Findings
To date, the TC remains superior to other forms of drug treatment in reducing recidivism and drug relapse amongst addicts who offend.

Originality/value
Outcomes of this review highlighted the importance of aftercare in providing transitional support; a fundamental aspect of treatment necessary for success and for maintaining long-term recovery post release.
Protein- and RNA-Enhanced Fermentation by Gut Microbiota of the Earthworm Lumbricus terrestris
Authors: Zeibich Lydia , Schmidt Oliver , Drake Harold L. 
Published: March 2018

ABSTRACTEarthworms are a dominant macrofauna in soil ecosystems and have determinative effects on soil fertility and plant growth. These invertebrates feed on ingested material, and gizzard-linked disruption of ingested fungal and bacterial cells is conceived to provide diverse biopolymers in the anoxic alimentary canals of earthworms. Fermentation in the gut is likely important to the utilization of ingested biopolymer-derived compounds by the earthworm. This study therefore examined the fermentative responses of gut content-associated microbes of the model earthwormLumbricus terrestristo (i) microbial cell lysate (to simulate gizzard-disrupted cells) and (ii) dominant biopolymers of such biomass, protein, and RNA. The microbial cell lysate augmented the production of H2, CO2, and diverse fatty acids (e.g., formate, acetate, propionate, succinate, and butyrate) in anoxic gut content microcosms, indicating that the cell lysate triggered diverse fermentations. Protein and RNA also augmented diverse fermentations in anoxic microcosms of gut contents, each yielding a distinct product profile (e.g., RNA yielded H2and succinate, whereas protein did not). The combined product profile of protein and RNA treatments was similar to that of cell lysate treatments, and 16S rRNA-based analyses indicated that many taxa that responded to cell lysate were similar to taxa that responded to protein or RNA. In particular, protein stimulatedPeptostreptococcaceae,Clostridiaceae, andFusobacteriaceae, whereas RNA stimulatedAeromonadaceae. These findings demonstrate the capacity of gut-associated obligate anaerobes and facultative aerobes to catalyze biopolymer-driven fermentations and highlight the potential importance of protein and RNA as substrates linked to the overall turnover dynamics of organic carbon in the alimentary canal of the earthworm.IMPORTANCEThe subsurface lifestyle of earthworms makes them an unnoticed component of the terrestrial biosphere. However, the propensity of these invertebrates to consume their home, i.e., soil and litter, has long-term impacts on soil fertility, plant growth, and the cycling of elements. The alimentary canals of earthworms can contain up to 500 ml anoxic gut content per square meter of soil, and ingested soil may contain 109or more microbial cells per gram dry weight, considerations that illustrate that enormous numbers of soil microbes are subject to anoxia during gut passage. Feeding introduces diverse sources of biopolymers to the gut, and the gut fermentation of biopolymers could be important to the transformation of matter by the earthworm and its capacity to utilize fermentation-derived fatty acids. Thus, this study examined the capacity of microbes in earthworm gut contents to ferment protein and RNA, dominant biopolymers of cells that become disrupted during gut passage.