bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering the interstrand crosslink DNA repair network expressed byTrypanosoma brucei
Authors: Dattani Ambika , Wilkinson Shane 
Published: February 2019

AbstractInterstrand crosslinks (ICLs) represent a highly toxic form of DNA damage that can block essential biological processes including DNA replication and transcription. To combat their deleterious effects all eukaryotes have developed cell cycle-dependent repair strategies that coopt various factors from ‘classical’ DNA repair pathways to resolve such lesions. Here, we report thatTrypanosoma brucei, the causative agent of African trypanosomiasis, possesses such systems that show some intriguing differences to those mechanisms expressed in other organisms. Following the identification of trypanosomal homologues encoding for CSB, EXO1, SNM1, MRE11, RAD51 and BRCA2, gene deletion coupled with phenotypic studies demonstrated that all the above factors contribute to this pathogen’s ICL REPAIRtoire with their activities split across two epistatic groups. We show that one network, which encompasses TbCSB, TbEXO1 and TbSNM1, may operate throughout the cell cycle to repair ICLs encountered by transcriptional detection mechanisms while the other relies on homologous recombination enzymes that together may resolve lesions responsible for the stalling of DNA replication forks. By unravelling and comparing theT. bruceiICL REPAIRtoire to those systems found in its host, targets amenable to inhibitor design may be identified and could be used alongside trypanocidal ICL-inducing agents to exacerbate their effects.Author summaryParasites belonging to theTrypanosoma bruceicomplex cause a human and animal infections collectively known as African trypanosomiasis. Drugs used against these diseases are problematic as medical supervision is required for administration, they are costly, have limited efficacy, may cause unwanted side effects while drug resistance is emerging. Against this backdrop, there is a need for new therapies targeting these neglected tropical diseases. Previous studies have shown compounds that induce DNA interstrand crosslinks (ICLs) formation are effective trypanocidal agents with the most potent invariably functioning as prodrugs. Despite the potential of ICL-inducing compounds to treat African trypanosomiasis little is known about the ICL repair mechanisms expressed by trypanosomes. Using a combination of gene deletion and epistatic analysis we report the first systematic dissection of how ICL repair might operate inT. brucei, a diverged eukaryote. It sheds light on the conservation and divergence of ICL repair in one of only a handful of protists that can be studied genetically, and offers the promise of developing or exploiting ICL-causing agents as new anti-parasite therapies. These findings emphasise the novelty and importance of understanding ICL repair inT. bruceiand, more widely, in non-model eukaryotes.
PhotorhabdusDam methyltransferase overexpression impairs virulence of the nemato-bacterial complex in insects
Authors: Payelleville Amaury , Blackburn Dana , Lanois Anne , Pagès Sylvie , Cambon Marine , Ginibre Nadège , Clarke David , Givaudan Alain , Brillard Julien 
Published: February 2019

AbstractPhotorhabdus luminescensis an entomopathogenic bacterium found in symbiosis with the nematodeHeterorhabditis. Dam DNA methylation is involved in the pathogenicity of many bacteria, includingP. luminescens,whereas studies about the role of bacterial DNA methylation during symbiosis are scarce. The aim of this study was to determine the role of Dam DNA methylation inP. luminescenssymbiosis withH. bacteriophora. We constructed a strain overexpressingdamby inserting an additional copy of thedamgene under the control of a constitutive promoter in the chromosome ofP. luminescensand then achieved association between this recombinant strain and nematodes. Thedamoverexpressing strain was able to feed the nematodein vitroandin vivosimilarly as a control strain, and to re-associate with Infective Juvenile (IJ) stages in the insect. No difference in the amount of emerging IJs from the cadaver was observed between the two strains. Compared to the nematode in symbiosis with the control strain, a significant increase in LT50was observed during insect infestation with the nematode associated with thedamoverexpressing strain. These results suggest that theP. luminescensDam plays a role in the pathogenicity of the nemato-bacterial complex.
Recombinant vector vaccines and within-host evolution
Authors: Bull James , Nuismer Scott L. , Antia Rustom 
Published: February 2019

AbstractMany recombinant vector vaccines are capable of replication within the host. They consist of a fully competent vector backbone engineered to express an antigen from a foreign transgene. From the perspective of viral replication, the transgene is not only dispensable but may even be intrinsically detrimental. Thus vaccine revertants that delete the transgene may evolve to dominate the within-host population and in doing so reduce the antigenicity of the vaccine. We apply mathematical and computational models to study this process, including the dynamics of vaccine and revertant growth plus the dynamics of innate and adaptive immunity. Although the selective basis of vaccine evolution is easy to comprehend, the immunological consequences are not. One complication is that, despite possible fitness differences between vaccine and revertant, the opportunity for vaccine evolution is limited by the short period of growth before the viral population is cleared. Even less obvious, revertantper sedoes not interfere with immunity to vaccine except as the revertant suppresses vaccine abundance; the magnitude of this interference depends on mechanisms and timing of viral suppression. Adaptive immunity targeting the foreign antigen is also a possible basis of vaccine inferiority, but it is not worsened by vaccine evolution. Overall, we find that within-host vaccine evolution can sometimes matter to the adaptive immune response targeting the foreign antigen, but even when it does matter, simple principles of vaccine design and the control of inoculum composition can largely mitigate the effects.Author SummaryRecombinant vector vaccines are live replicating viruses that are engineered to carry extra genes derived from a pathogen – and these produce proteins against which we want to generate immunity. These genes may evolve to be lost during the course of replication within an individual, and there is a concern that this can severely limit the vaccine’s efficacy. The dynamics of this process are studied here with mathematical models. The potential for vaccine evolution is somewhat reduced by the short-term growth of the vaccine population before it is suppressed by the immune response. Even when within-host evolution can be a problem, the models show that increasing the vaccine inoculum size or ensuring that the inoculum is mostly pure vaccine can largely avoid the loss of immunity arising from evolution.
Integrating and extending competing intention models to understand the entrepreneurial intention of senior university students
Authors: Eid Riyad , Badewi Amgad , Selim Hassan , El-Gohary Hatem 
Published: February 2019

PurposeThe growing interest in the development of entrepreneurial intention (EI) that has increased the importance of theories that explain and anticipate the tendency among individuals to start a new business. However, most of these theories focus on the relationship between entrepreneurs perceptions and their intention and ignore the cognitive and psychological characteristics that might configure their perceptions. Therefore, the purpose of this paper is to integrate the theory of planned behaviour (TPB) with the entrepreneurial event model (EEM) and to extend the combined model to include the personality characteristics of an entrepreneur that might shape the perceptions and intentions.Design/methodology/approachThis study uses a sample of 688 senior university students (Emirati nationals, 91.2 per cent and expatriates, 8.8 per cent) and employs positivist research with a quantitative approach, adopting a survey strategy through questionnaires and structural equation modelling.FindingsThe results demonstrate the relevance and robustness of the suggested combined and extended model in the prediction of intention on the part of senior university students to become entrepreneurs (explained variance=73.3 per cent) based on survey data (2017;n= 688).Originality/valueThe main contribution of this paper lies not only in the integration of the TPB and the EEM, but also in extending the two theories on which it is based through adding entrepreneurial personality characteristics and an explanation of the mechanism through which entrepreneurial perceptions and EI develop.
Categorical differences of hotel brand personality
Authors: Su Na , Reynolds Dennis 
Published: February 2019

PurposeThis study aims to differentiate the brand personality of four basic hotel categories (e.g. limited-service, selected-service, full-service and luxury hotels) to draw an overall landscape of the lodging industry on symbolic attributes.Design/methodology/approachAn online survey was conducted to assess the brand personality of eight popular hotel brands competing in the US market (two brands for each price category) by using Aaker’s (1997) brand personality scale. The categorical difference in brand personality was compared at both of the dimensional and individual trait level.FindingsThis study draws a picture of brand personality for four prevailing hotel categories in the US market. It suggests exciting luxury hotels, sincere select-service hotels and rugged limited-service hotels, but no distinctive personality for full-service hotels. This study positions the pros and cons of each hotel category. For instance, it shows at the dimensional level, full-service hotels advance select-service hotels in excitement but fall behind in sincerity. At the individual trait level, full-service hotels strike customers as contemporary, up-to-date and good-looking, but disappoint customers on the features like honest and wholesome.Practical implicationsThis study informs hotel brand companies and hotel investors with the pros and cons of each hotel category to assist them to improve their marketing or investment strategies.Originality/valueAlthough brand personality has been often used to assess hotel brand’s difference, it has been rarely used to capture the categorical difference. This study adds new insights to hotel banding practice by comparing different categories on symbolic attributes.
Effect of medium carbon steel microstructure on tensile strength and fatigue crack growth
Authors: Mossaab Blaoui Mohammed , Zemri Mokhtar , Arab Mustapha 
Published: February 2019

Purpose
The purpose of this paper is to evaluate the effects of medium carbon steel microstructure on the tensile strength and fatigue crack growth (FCG) behavior.

Design/methodology/approach
To achieve this aim, four different heat treatment methods (normalizing, quenching, tempering at 300°C and tempering at 600°C) were considered. Microstructural evolution was investigated by scanning electron microscopy. FCG rate tests were conducted on the resultant microstructures with compact tension specimens at room temperature by a standard testing method.

Findings
The results show that the normalized microstructure had the largest number of cycles to failure, indicating a high fatigue resistance, followed by the as received, tempered at 600°C, tempered at 300°C and quenched microstructure.

Originality/value
The paper shows the influence of the microstructure on the fatigue-propagation behavior with the definition of the Paris parameters of each heat treatment condition.
Static and dynamic elastic moduli of organic‐rich chalk
Authors: Shitrit Omri , Hatzor Yossef H. , Feinstein Shimon , Palchik Vyacheslav , Vinegar Harold J. 
Published: February 2019

ABSTRACTThe elastic moduli and anisotropy of organic‐rich rocks are of great importance to geoengineering and geoprospecting of oil and gas reservoirs. In this paper, we probe into the static and dynamic moduli of the Ghareb–Mishash chalk through laboratory measurements and new analytical approaches. We define a new anisotropy parameter, ‘hydrostatic strain ratio’ (Ω), which describes the differential contraction of anisotropic rocks consequent to hydrostatic compression. Ω depends on the C11, C12, C13 and C33 stiffness constants of a transversely isotropic material, and therefore enables a unique insight into the anisotropic behaviour of TI rocks. Ω proves more sensitive to anisotropy within the weak anisotropy range, when compared with Thomsen's ε and γ parameters. We use Ω to derive static moduli from triaxial compression tests performed on a single specimen. This is done by novel employment of a hydrostatic‐deviatoric combination for transversely isotropic elastic stiffnesses. Dynamic moduli are obtained from acoustic velocities measurements. We find that the bedding‐normal velocities are described well by defining kerogen as the load‐supporting matrix in a Hashin–Shtrikman model (‘Hashin–Shtrikman (HS) kerogen’). The dynamic moduli of the Ghareb–Mishash chalk in dry conditions are significantly higher than the static moduli. The dynamic/static moduli ratio decreases from ∼4 to ∼2 with increasing kerogen content. Both the static and dynamic moduli decrease significantly with increasing porosity and kerogen content. The effect of porosity on them is two times stronger than the effect of kerogen.
Alternative Methods to SO2 for Microbiological Stabilization of Wine
Authors: Lisanti Maria Tiziana , Blaiotta Giuseppe , Nioi Claudia , Moio Luigi 
Published: February 2019

AbstractThe use of sulfur dioxide (SO2) as wine additive is able to ensure both antioxidant protection and microbiological stability. In spite of these undeniable advantages, in the last two decades the presence of SO2 in wine has raised concerns about potential adverse clinical effects in sensitive individuals. The winemaking industry has followed the general trend towards the reduction of SO2 concentrations in food, by expressing at the same time the need for alternative control methods allowing reduction or even elimination of SO2. In the light of this, research has been strongly oriented toward the study of alternatives to the use of SO2 in wine. Most of the studies have focused on methods able to replace the antimicrobial activity of SO2. This review article gives a comprehensive overview of the current state‐of‐the‐art about the chemical additives and the innovative physical techniques that have been proposed for this purpose. After a focus on the chemistry and properties of SO2 in wine, as well as on wine spoilage and on the conventional methods used for the microbiological stabilization of wine, recent advances on alternative methods proposed to replace the antimicrobial activity of SO2 in winemaking are presented and discussed. Even though many of the alternatives to SO2 showed good efficacy, nowadays no other physical technique or additive can deliver the efficacy and broad spectrum of action as SO2 (both antioxidant and antimicrobial), therefore the alternative methods should be considered a complement to SO2 in low‐sulfite winemaking, rather than being seen as its substitutes.
Forensic Application of Analytical Mechanics in Fatal Fall From a Height
Authors: Tsai Wu‐ting , Chang Chia‐Yun , Hu Chia‐I 
Published: February 2019

AbstractFatal fall from a height initiated with a swinging motion on the sagittal plane of the victim's body is examined. Method of analytical mechanics is adopted to establish the functional relations between the swinging angle of the body and the force needed to sustain the body until release, and the amount of the horizontal displacement that would occur after release. The analysis is applied to support an expert opinion presented in a criminal court in which two accused were convicted of murder for dropping a female victim from a bridge. The results indicate that it is unlikely for the body to locate as recorded by the police investigation report in the case. This study demonstrates that a straightforward mechanical analysis can be utilized to examine uncommon falling scenarios.
An Alternative Method to Using a Mandibulometer
Authors: Garvin Heather M. , Severa Kieran 
Published: February 2019

AbstractMandibular length, mandibular angle, and maximum ramus height measurements used during forensic evaluation of skeletal remains require use of a mandibulometer. This study presents a new method of taking these measurements from images, so that practitioners without access to an expensive mandibulometer or those working with 3D models (e.g., CT scans) can collect and utilize these measurements. Ten trials performed on a sample of 45 mandibles were used to compare measurements collected from photographs and images extracted from 3D surface scans to those collected with a mandibulometer, including intra‐ and inter‐observer analyses. All technical error of measurement (TEM) values were less than 2 mm regardless of observer, trial, or method. Relative TEM values were less than 2% for all except mandibular length (2.10%) and ramus height (2.32%) for the right versus left photographs. Results are comparable with mandibulometer error rates, indicating that the proposed method is accurate and reliable.
Hydrodynamic Modeling Improves Green River Reconnection with Floodplain Wetlands for Endangered Fish Species Recovery
Authors: Caruso Brian S. , Newman Brian , Econopouly Thomas 
Published: February 2019

AbstractWe performed two‐dimensional (2D) hydrodynamic modeling to aid recovery of the endangered razorback sucker (Xyrauchen texanus) by reconnecting the Green River with its historic bottomland floodplain wetlands at Ouray National Wildlife Refuge, Utah. Reconnection allows spring flood flows to overtop the river levee every two to three years, and passively transport razorback sucker larvae to the wetlands to grow in critical habitat. This study includes (1) river hydrologic analysis, (2) simulation of a levee breach/weir, overtopping of river flood flows, and 2D flow through the wetlands using Hydrologic Engineering Center River Analysis System 2D, and (3) modeling flow and restoration scenarios. Indicators of hydrologic alteration were used to evaluate river flow metrics, in particular flood magnitudes, frequency, and duration. Results showed a target spring flow of 16,000 cfs (453 m3/s) and a levee breach elevation of 4,663 ft (1,421 m) amsl would result in a median flow >6,000 acre‐feet (7.4 million m3) over five days into the wetlands, which is adequate for razorback sucker larvae transport and rearing. Modeling of flow/restoration scenarios showed using gated water control structures and passive low‐water crossings between wetland units can provide adequate control of flow movement into and storage in multiple units. Levee breaching can be a relatively simple, cost‐effective method to reconnect rivers and historic floodplains, and hydrodynamic modeling is an important tool for analyzing and designing wetland reconnection.
KEYNOTE: Global Extinction and Animal Welfare: Two Priorities for Effective Altruism
Authors: Ng Yew‐Kwang 
Published: February 2019

AbstractEffective altruism should ultimately be for the promotion of aggregate welfare. Broad altruism does not confine welfare to humans only. Thus, two priorities for broad and effective altruism may include reducing the probabilities of global extinction and the promotion of animal welfare. The former is important because if we become extinct, we lose the enormous amount of welfare into the far future. Also, we are faced with extinction probabilities that could be reduced, including through better environmental protection. Moreover, if we can avoid extinction, we will likely be able to increase our welfare enormously through such scientific and technological breakthroughs like brain stimulation and genetic engineering. Whether artificial intelligence may threaten our survival soon is also briefly discussed. An effective way to promote animal welfare is to reduce animal suffering at small or even negative costs for humans.
Alteration in gene expression profile of thymomas with or without myasthenia gravis linked with the nuclear factor‐kappaB/autoimmune regulator pathway to myasthenia gravis pathogenesis
Authors: Guo Feng , Wang Chun‐Yang , Wang Shuo , Zhang Jun , Yan Yi‐Jie , Guan Zhi‐Yu , Meng Fan‐Jie 
Published: February 2019

BackgroundTo investigate the gene expression profile of a set of candidate genes for a better understanding of the molecular mechanism underlying the pathogenesis of thymoma with or without myasthenia gravis.MethodsThymoma patients and thymoma patients with myasthenia gravis were analyzed using microarray profiling to identify significant changes in gene expression of autoimmune regulator pathway genes including AIRE, IL‐7R, CHRNA3, SYMD1, THRA, and CAV3.ResultsAcross all of our samples, we found that 1484 mRNAs were upregulated and 770 were downregulated in thymoma patients compared with thymoma with myasthenia gravis patients. Gene ontology and pathway analysis revealed that a large number of genes participated in cellular functions for humoral immune response, sequence‐specific DNA binding RNA polymerase II transcription factor activity, positive regulation of gene expression, regulation of neuron projection development, extracellular ligand‐gated ion channel activity, positive regulation of striated muscle cell differentiation, and regulation of nuclear factor‐kappaB import into the nucleus.ConclusionOur results revealed genetic differences between thymomas and myasthenia gravis, and identified the key candidate genes/pathways for molecular mechanism.
C‐reactive protein to albumin ratio is a key indicator in a predictive model for anastomosis leakage after esophagectomy: Application of classification and regression tree analysis
Authors: Shao Chen‐Ye , Liu Kai‐Chao , Li Chu‐Ling , Cong Zhuang‐Zhuang , Hu Li‐Wen , Luo Jing , Diao Yi‐Fei , Xu Yang , Ji Sai‐Guang , Qiang Yong , Shen Yi 
Published: February 2019

BackgroundAnastomotic leakage (AL), a serious complication after esophagectomy, might impair patient quality of life, prolong hospital stay, and even lead to surgery‐related death. The aim of this study was to show a novel decision model based on classification and regression tree (CART) analysis for the prediction of postoperative AL among patients who have undergone esophagectomy.MethodsA total of 450 patients (training set: 356; test set: 94) with perioperative information were included. A decision tree model was established to identify the predictors of AL in the training set, which was validated in the test set. A receiver operating characteristic curve was also created to illustrate the diagnostic ability of the decision model.ResultsA total of 12.2% (55/450) of the 450 patients suffered AL, which was diagnosed at median postoperative day 7 (range: 6–16). The decision tree model, containing surgical duration, postoperative lymphocyte count, and postoperative C‐reactive protein to albumin ratio, was established by CART analysis. Among the three variables, the postoperative C‐reactive protein to albumin ratio was identified as the most important indicator in the CART model with normalized importance of 100%. According to the results validated in the test set, the sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy of the prediction model were 80%, 98.8%, 88.9%, 97.6%, and 96.8%, respectively. Moreover, the area under the receiver operating characteristic curve was 0.95.ConclusionThe decision model based on CART analysis presented good performance for predicting AL, and might allow the early identification of patients at high risk.