bluuebunny/crossref_metadata_2025 huggingface dataset:
Nitrogen use efficiency is regulated by interacting proteins relevant to development in wheat
Authors: Lei Lei , Li Genqiao , Zhang Hailin , Powers Carol , Fang Tilin , Chen Yihua , Wang Shuwen , Zhu Xinkai , Carver Brett F. , Yan Liuling
Published: November 2017

Wheat (Triticum aestivum) has low nitrogen use efficiency (NUE). The genetic mechanisms controlling NUE are unknown. Positional cloning of a major quantitative trait locus for N‐related agronomic traits showed that the vernalization gene TaVRN‐A1 was tightly linked with TaNUE1, the gene shown to influence NUE in wheat. Because of an Ala180/Val180 substitution, TaVRN‐A1a and TaVRN‐A1b proteins interact differentially with TaANR1, a protein encoded by a wheat orthologue of Arabidopsis nitrate regulated 1 (ANR1). The transcripts of both TaVRN‐A1 and TaANR1 were down‐regulated by nitrogen. TaANR1 was functionally characterized in TaANR1::RNAi transgenic wheat, and in a natural mutant with a 23‐bp deletion including 10‐bp at the 5′ end of intron 5 and 13‐bp of exon 6 in gDNA sequence in its gDNA sequence, which produced transcript that lacked the full 84‐bp exon 6. Both TaANR1 and TaHOX1 bound to the Ala180/Val180 position of TaVRN‐A1. Genetically incorporating favourable alleles from TaVRN‐A1, TaANR1 and TaHOX1 increased grain yield from 9.84% to 11.58% in the field. Molecular markers for allelic variation of the genes that regulate nitrogen can be used in breeding programmes aimed at improving NUE and yield in novel wheat cultivars.
Overexpression of the class I homeodomain transcription factor TaHDZipI‐5 increases drought and frost tolerance in transgenic wheat
Authors: Yang Yunfei , Luang Sukanya , Harris John , Riboni Matteo , Li Yuan , Bazanova Natalia , Hrmova Maria , Haefele Stephan , Kovalchuk Nataliya , Lopato Sergiy
Published: November 2017

Characterization of the function of stress‐related genes helps to understand the mechanisms of plant responses to environmental conditions. The findings of this work defined the role of the wheat TaHDZipI‐5 gene, encoding a stress‐responsive homeodomain–leucine zipper class I (HD‐Zip I) transcription factor, during the development of plant tolerance to frost and drought. Strong induction of TaHDZipI‐5 expression by low temperatures, and the elevated TaHDZipI‐5 levels of expression in flowers and early developing grains in the absence of stress, suggests that TaHDZipI‐5 is involved in the regulation of frost tolerance at flowering. The TaHDZipI‐5 protein behaved as an activator in a yeast transactivation assay, and the TaHDZipI‐5 activation domain was localized to its C‐terminus. The TaHDZipI‐5 protein homo‐ and hetero‐dimerizes with related TaHDZipI‐3, and differences between DNA interactions in both dimers were specified at 3D molecular levels. The constitutive overexpression of TaHDZipI‐5 in bread wheat significantly enhanced frost and drought tolerance of transgenic wheat lines with the appearance of undesired phenotypic features, which included a reduced plant size and biomass, delayed flowering and a grain yield decrease. An attempt to improve the phenotype of transgenic wheat by the application of stress‐inducible promoters with contrasting properties did not lead to the elimination of undesired phenotype, apparently due to strict spatial requirements for TaHDZipI‐5 overexpression.
Addressing the wicked problem of childhood trauma through a nursing and cooperative extension system collaboration
Authors: Foli Karen J. , Woodcox Stephanie , Kersey Susan , Zhang Lingsong
Published: November 2017

The purpose of this clinical concept report is to describe a public health project in rural Indiana that addressed the complex social issue or “wicked problem” of childhood trauma. The project was implemented through a unique partnership between nursing faculty and Cooperative Extension Educators, community‐based workers who are associated with fulfilling the mission of Land Grant Universities. The core focus of the project entailed a nurse and a Cooperative Extension Educator co‐teaching trauma‐informed parenting classes to rural dwelling, kinship caregivers. Kinship caregivers are often grandparents who assume the parenting role after the child has been removed from the birth parents’ care. The trauma‐informed curriculum was developed by experts in child trauma and is available through the National Child Traumatic Stress Network. The unique partnership provided insight into the different missions of the two organizations, different values and workflow metrics, and different schedules, which at times proved to be barriers to implementation. This discussion focuses on deconstructing the goals and objectives of the project and retrospectively, describing recommendations so that public health nurses may partner with Extension Educators in their communities for optimal project success.
Investigating Operational Predictors of Future Financial Distress in the US Airline Industry
Authors: Alan Yasin , Lapré Michael A.
Published: November 2017

We investigate the predictive power of operational performance on future financial distress in the context of the US airline industry. We focus on four areas of operational performance: revenue management, operational efficiency, service quality, and operational complexity. Using quarterly data from 1988 through 2013, we find that airlines that have inferior revenue management, lower aircraft utilization, and higher operational complexity face higher future financial distress. Interestingly, average service quality, measured by on‐time performance and mishandled baggage rate, is not associated with future financial distress, but extreme service failures, measured by long delays (over two hours) and passenger complaints with the government regarding mishandled bags, have a positive association with future financial distress. Using the association between current operational performance and future financial distress, we build a model to predict financial distress. Out‐of‐sample analyses show that our forecasting model outperforms a financial ratio‐based benchmark model up‐to eight quarters before the measurement of financial distress. Our findings inform firms, regulators, and investors by demonstrating that operational performance metrics contain useful information to predict future financial distress.
Control networks and hubs
Authors: Gratton Caterina , Sun Haoxin , Petersen Steven E.
Published: November 2017

Executive control functions are associated with frontal, parietal, cingulate, and insular brain regions that interact through distributed large‐scale networks. Here, we discuss how fMRI functional connectivity can shed light on the organization of control networks and how they interact with other parts of the brain. In the first section of our review, we present convergent evidence from fMRI functional connectivity, activation, and lesion studies that there are multiple dissociable control networks in the brain with distinct functional properties. In the second section, we discuss how graph theoretical concepts can help illuminate the mechanisms by which control networks interact with other brain regions to carry out goal‐directed functions, focusing on the role of specialized hub regions for mediating cross‐network interactions. Again, we use a combination of functional connectivity, lesion, and task activation studies to bolster this claim. We conclude that a large‐scale network perspective provides important neurobiological constraints on the neural underpinnings of executive control, which will guide future basic and translational research into executive function and its disruption in disease.
Which Fire to Extinguish First? A Risk‐Informed Approach to Emergency Response in Oil Terminals
Authors: Khakzad Nima
Published: November 2017

The performance of fire protection measures plays a key role in the prevention and mitigation of fire escalation (fire domino effect) in process plants. In addition to passive and active safety measures, the intervention of firefighting teams can have a great impact on fire propagation. In the present study, we have demonstrated an application of dynamic Bayesian network to modeling and safety assessment of fire domino effect in oil terminals while considering the effect of safety measures in place. The results of the developed dynamic Bayesian network—prior and posterior probabilities—have been combined with information theory, in the form of mutual information, to identify optimal firefighting strategies, especially when the number of fire trucks is not sufficient to handle all the vessels in danger.
Unemployment, rural–urban migration and environmental regulation
Authors: Kuralbayeva Karlygash
Published: November 2017

This paper develops a general equilibrium model that incorporates specific features pertaining to developing countries: a large informal sector and rural–urban migration. A calibrated version of the model is used to study the effects of energy tax changes and a reduction in agricultural‐sector energy subsidies on labor market outcomes. The results indicate that the incidence of energy taxes is partly shifted on to the rural sector through rural–urban migration. The results thus highlight the importance of modeling the features particular to developing countries and the economic general equilibrium effects when assessing the impact of environmental taxation in those countries.
Substance use disorder and compulsory commitment to care: a care‐ethical decision‐making framework
Authors: Nicolini Marie , Vandenberghe Joris , Gastmans Chris
Published: November 2017

In the era of deinstitutionalisation of psychiatric patients, steady or even increasing rates of compulsory commitment to care (CCC) are an intriguing phenomenon to analyse. From a clinical, legal and ethical perspective, CCC continues to be a controversial practice in psychiatry, and perhaps even more so when applied to patients with severe substance use disorder (SUD). Several reasons make it controversial. The lack of consensus about the benefits of CCC and professional disagreement about what mental illness and autonomy mean in the case of SUD make it difficult to apply ethically sound clinical decision‐making in CCC. Also, the medico‐legal framework underlying CCC use sometimes appears to foster the use of reductionist clinical evaluation. Layered on top of these issues is how stakeholders view coercion. There is a discrepancy between clinicians’ and patients’ perception of coercion, which leads to clinician–patient differences on whether CCC is necessary. Moreover, the way in which the evaluation is typically carried out influences patients’ perception of coercion and subsequently their motivation for participating fully in treatment. In this article, we explore the value of care ethics, often applied to care practices such as nursing, when applied to more procedural medical practices, such as decision‐making regarding CCC. The care‐ethical approach views decision‐making as part of a dynamic care process, within which the lived experience, interpretative dialogue and promotion of dignity are core features. Embracing this new framework means a paradigm shift in when the therapeutic relationship begins, namely, investing in it occurs while conducting an evaluation for a possible CCC procedure. Unlike in current typical evaluations, early cultivation of the therapeutic relationship enables the patient to participate in the definition of his needs, reduces perceived coercion and negative emotions and enhances treatment motivation. Finally, implications of this novel approach for clinical practice are formulated and discussed.
The Integration of Racial and Ethnic Minorities into White Congregations
Authors: C. Martinez Brandon
Published: November 2017

Drawing from the homophily principle and organizational ecology theory, I follow previous literature and predict racial minorities will have lower levels of belonging and commitment when attending predominantly white congregations. Going beyond this literature, I incorporate contemporary racial stratification literature and propose integration into white congregations would vary by racial group as a result of the differing symbolic group positioning of minorities in America's racial hierarchy. Results from multilevel models using a national dataset generally support my hypotheses. The findings from this study reveal distinctions between minority racial groups within predominantly white congregations. Thus, the homophily principle and organizational ecology are not sufficient when studying race within congregations, as it is not enough to rely solely on the numeric representation of racial groups in congregations without taking into account the social positioning of these groups. These results, their implications, and potential directions for future studies are further discussed.
RePHILL: protocol for a randomised controlled trial of pre‐hospital blood product resuscitation for trauma
Authors: Smith I. M. , Crombie N. , Bishop J. R. , McLaughlin A. , Naumann D. N. , Herbert M. , Hancox J. M. , Slinn G. , Ives N. , Grant M. , Perkins G. D. , Doughty H. , Midwinter M. J. ,   on behalf of the RePHILL Trial Collaborators
Published: November 2017

Objectives

To describe the ‘Resuscitation with Pre‐HospItaL bLood products’ trial (RePHILL) – a multi‐centre randomised controlled trial of pre‐hospital blood product (PHBP) administration vs standard care for traumatic haemorrhage.

Background

PHBP are increasingly used for pre‐hospital trauma resuscitation despite a lack of robust evidence demonstrating superiority over crystalloids. Provision of PHBP carries additional logistical and regulatory implications, and requires a sustainable supply of universal blood components.

Methods

RePHILL is a multi‐centre, two‐arm, parallel group, open‐label, phase III randomised controlled trial currently underway in the UK. Patients attended by a pre‐hospital emergency medical team, with traumatic injury and hypotension (systolic blood pressure <90 mmHg or absent radial pulse) believed to be due to traumatic haemorrhage are eligible. Exclusion criteria include age <16 years, blood product receipt on scene prior to randomisation, Advanced Medical Directive forbidding blood product administration, pregnancy, isolated head injury and prisoners. A total of 490 patients will be recruited in a 1 : 1 ratio to receive either the intervention (up to two units of red blood cells and two units of lyophilised plasma) or the control (up to four boluses of 250 mL 0.9% saline). The primary outcome measure is a composite of failure to achieve lactate clearance of ≥20%/h over the first 2 hours after randomisation and all‐cause mortality between recruitment and discharge from the primary receiving facility to non‐acute care. Secondary outcomes include pre‐hospital time, coagulation indices, in‐hospital transfusion requirements and morbidity.

Results

Pilot study recruitment began in December 2016. Approval to proceed to the main trial was received in June 2017. Recruitment is expected to continue until 2020.

Conclusions

RePHILL will provide high‐quality evidence regarding the efficacy and safety of PHBP resuscitation for trauma.
In premature infants there is no decrease in 24‐hour posttransfusion allogeneic red blood cell recovery after 42 days of storage
Authors: Nalbant Demet , Cancelas José A. , Mock Donald M. , Kyosseva Svetlana V. , Schmidt Robert L. , Cress Gretchen A. , Zimmerman M. Bridget , Strauss Ronald G. , Widness John A.
Published: November 2017

BACKGROUND

Critically ill preterm very‐low‐birthweight (VLBW) neonates (birthweight ≤ 1.5 kg) frequently develop anemia that is treated with red blood cell (RBC) transfusions. Although RBCs transfused to adults demonstrate progressive decreases in posttransfusion 24‐hour RBC recovery (PTR24) during storage—to a mean of approximately 85% of the Food and Drug Administration—allowed 42‐day storage—limited data in infants indicate no decrease in PTR24 with storage.

STUDY DESIGN AND METHODS

We hypothesized that PTR24 of allogeneic RBCs transfused to anemic VLBW newborns: 1) will be greater than PTR24 of autologous RBCs transfused into healthy adults and 2) will not decrease with increasing storage duration. RBCs were stored at 4°C for not more than 42 days in AS‐3 or AS‐5. PTR24 was determined in 46 VLBW neonates using biotin‐labeled RBCs and in 76 healthy adults using 51Cr‐labeled RBCs. Linear mixed‐model analysis was used to estimate slopes and intercepts of PTR24 versus duration of RBC storage.

RESULTS

For VLBW newborns, the estimated slope of PTR24 versus storage did not decrease with the duration of storage (p = 0.18) while for adults it did (p < 0.0001). These estimated slopes differed significantly in adults compared to newborns (p = 0.04). At the allowed 42‐day storage limit, projected mean neonatal PTR24 was 95.9%; for adults, it was 83.8% (p = 0.0002).

CONCLUSIONS

These data provide evidence that storage duration of allogeneic RBCs intended for neonates can be increased without affecting PTR24. This conclusion supports the practice of transfusing RBCs stored up to 42 days for small‐volume neonatal transfusions to limit donor exposure.
Evaluation of a lateral flow–based technology card for blood typing using a simplified protocol in a model of extreme blood sampling conditions
Authors: Clavier Benoît , Pouget Thomas , Sailliol Anne
Published: November 2017

BACKGROUND

Life‐threatening situations requiring blood transfusion under extreme conditions or in remote and austere locations, such as the battlefield or in traffic accidents, would benefit from reliable blood typing practices that are easily understood by a nonscientist or nonlaboratory technician and provide quick results.

STUDY DESIGN AND METHODS

A simplified protocol was developed for the lateral flow–based device MDmulticard ABO‐D‐Rh subgroups‐K. Its performance was compared to a reference method (PK7300, Beckman Coulter) in native blood samples from donors. The method was tested on blood samples stressed in vitro as a model of hemorrhage cases (through hemodilution using physiologic serum) and dehydration (through hemoconcentration by removing an aliquot of plasma after centrifugation), respectively.

RESULTS

A total of 146 tests were performed on 52 samples; 126 in the hemodilution group (42 for each native, diluted 1/2, and diluted 1/4 samples) and 20 in the hemoconcentration group (10 for each native and 10% concentrated samples). Hematocrit in the tested samples ranged from 9.8% to 57.6% while hemoglobin levels ranged from 3.2 to 20.1 g/dL. The phenotype profile detected with the MDmulticard using the simplified protocol resulted in 22 A, seven B, 20 O, and three AB, of which nine were D– and five were Kell positive. No discrepancies were found with respect to the results obtained with the reference method.

CONCLUSION

The simplified protocol for MDmulticard use could be considered a reliable method for blood typing in extreme environment or emergency situations, worsened by red blood cell dilution or concentration.
Organizational Maturity in Companies in Terms of Strategic Directions: Cases of ONEE, ONEP and Barid Al Maghrib
Authors: Mahir Fatima-Zahra , Rajâa Omar
Published: November 2017

In an environment characterized by globalization, several companies and groups are feeling increasing pressure on their competitiveness, innovation, market flexibility.... At the level of strategic management of the company and its operations, this pressure inevitably challenge the strategic direction put in place by the companies.The present study, based on survey data collected from 3 Moroccan groups, ONEE (National office of Electricity and drinking water), ONEP (National office of Drinking Water) and Morocco Post Group (Barid Al Maghrib), aims at a more in-depth understanding of the strategic direction. A concept that has been apprehended, mainly, by two approaches:- The comparative approach defined, in eight dimensions according to Venkatraman (1989) and Chan and al. (1997).- The recognized typological approach of Miles and Snow (1978) which includes defenders, analyzers and prospectors.The main objective of this research is first to analyze a literary review of these two approaches, then to project the different dimensions and theoretical characteristics on the empirical level.On the basis of questionnaires relating to the two approaches, we identified the main dimensions that characterizes each group, classified the groups according to their typologies, and we obtained as a result two groups as type "defender" and a group as type "Analyzer".
Impact of the Exposure to Entrepreneurship Education on Students’ Entrepreneurial Intentions: A Case - Based Study of the Higher Education in Brazil
Authors: Ching Hong Yuh , Kitahara José Renato
Published: November 2017

The objective of this paper is to examine the impact of the exposure to entrepreneurship education on students’ entrepreneurial intentions. This is an exploratory quantitative study. A questionnaire based on McClelland model was applied on a sample of 230 Business undergraduate students of a Brazilian university throughout a period of eight semesters. The following statistical tools were used - t-Student, ANOVA, Hierarchical Cluster, K-Means Cluster, Cross tabulation and Chi-Square. No differences were significant to discriminate gender, nor previous experiences on family business. Yet, there were no significant changes of entrepreneurial competencies factors mean values when considering longitudinal behavior in units of semesters in the period of 2014 to 2017. Although there are two groups representing different levels of intention to undertake, even the group with less intention presents mean value around and/or above the minimum threshold value (as 30) mentioned by McClelland. The results of all tests provide empirical evidences that allow confirming that the exposure to entrepreneurial education indeed influences and positively the students´ entrepreneurial intentions. The entrepreneurial education may not be only related to development of entrepreneurs or tied to the specifics of starting a business. It should also contribute to economic development, enterprising spirit and work skills among people aiming professional self-realization in various contexts. Two directions for policy intervention in the area of the higher education in Brazil are offered: entrepreneurship becomes an interdisciplinary program and be present in all courses and bring universities closer to the market by strengthening the entrepreneur ecosystem.
An Examination of the Qatari Licensure System: Giving Voice to Educators at Government-Funded Schools
Authors: Abu-Tineh Abdullah , Sadiq Hissa , Al-Mutawah Fatma , Chaaban Youmen
Published: November 2017

The issue of developing a comprehensive licensure system aligned with professional standards for teachers and school leaders has received considerable attention in recent years. As part of the Qatari educational reform in recent years, teachers and school leaders are held accountable to offer quality education for all students. The current study thus examined the experiences of educators in Qatar with the licensure process currently implemented at government-funded school. Using a survey study design, a total of 1,669 participants expressed their perceptions on the strengths and weaknesses of the licensure system, the professional standards, and the professional portfolio. Findings included participants’ beliefs on the importance of the licensure system in improving their performance, the necessity of using the professional standards as tools for professional growth and development, and the importance of refining the professional portfolio for authenticity and reliability. Documenting teachers’ and school leaders’ voices was fundamental in finding ways to successfully drive future developments of the licensure system. The findings may also provide implications for other countries interested in developing or refining their own appraisal systems.
Molecular adaptations of adipose tissue to 6 weeks of morning fasting vs. daily breakfast consumption in lean and obese adults
Authors: Gonzalez Javier T. , Richardson Judith D. , Chowdhury Enhad A. , Koumanov Francoise , Holman Geoffrey D. , Cooper Scott , Thompson Dylan , Tsintzas Kostas , Betts James A.
Published: November 2017

Key points

In lean individuals, 6 weeks of extended morning fasting increases the expression of genes involved in lipid turnover (ACADM) and insulin signalling (IRS2) in subcutaneous abdominal adipose tissue.

In obese individuals, 6 weeks of extended morning fasting increases IRS2 expression in subcutaneous abdominal adipose tissue.

The content and activation status of key proteins involved in insulin signalling and glucose transport (GLUT4, Akt1 and Akt2) were unaffected by extended morning fasting. Therefore, any observations of altered adipose tissue insulin sensitivity with extended morning fasting do not necessarily require changes in insulin signalling proximal to Akt.

Insulin‐stimulated adipose tissue glucose uptake rates are lower in obese versus lean individuals, but this difference is abolished when values are normalised to whole‐body fat mass. This suggests a novel hypothesis which proposes that the reduced adipose glucose uptake in obesity is a physiological down‐regulation to prevent excessive de novo lipogenesis.

This study assessed molecular responses of human subcutaneous abdominal adipose tissue (SCAT) to 6 weeks of morning fasting. Forty‐nine healthy lean (n = 29) and obese (n = 20) adults provided SCAT biopsies before and after 6 weeks of morning fasting (FAST; 0 kcal until 12.00 h) or daily breakfast consumption (BFAST; ≥700 kcal before 11.00 h). Biopsies were analysed for mRNA levels of selected genes, and GLUT4 and Akt protein content. Basal and insulin‐stimulated Akt activation and tissue glucose uptake rates were also determined. In lean individuals, lipid turnover and insulin signalling genes (ACADM and IRS2) were up‐regulated with FAST versus BFAST (ACADM: 1.14 (95% CI: 0.97–1.30) versus 0.80 (95% CI: 0.64–0.96), P = 0.007; IRS2: 1.75 (95% CI: 1.33–2.16) versus 1.09 (95% CI: 0.67–1.51), P = 0.03, respectively). In obese individuals, no differential (FAST versus BFAST) expression was observed in genes involved in lipid turnover (all P > 0.1). GLUT4, Akt protein content and insulin‐stimulated Akt phosphorylation were unaffected by FAST versus BFAST in both lean and obese cohorts (all P > 0.1). Lower insulin‐stimulated glucose uptake rates in obese versus lean individuals were eradicated when normalised to whole‐body fat mass (P = 0.416). We conclude that morning fasting up‐regulates lipid turnover genes in SCAT of lean individuals. Secondly, altered SCAT insulin sensitivity with morning fasting is unlikely to be explained by signalling proximal to Akt. Finally, lower insulin‐stimulated SCAT glucose uptake rates in obese individuals are proportional to whole‐body fat mass, suggesting a compensatory down‐regulation, presumably to prevent excessive de novo lipogenesis in adipose tissue. This trial was registered as ISRCTN31521726.
Analysis of Inertization Strategies for the Filtered Containment Venting System in Cofrentes Nuclear Power Plant
Authors: Fernández-Cosials Kevin , Jiménez Gonzalo , Serrano César , Ibáñez Luisa , Peinado Ángel
Published: November 2017

During a severe accident (SA) in a nuclear power plant (NPP), there are several challenges that need to be faced. To coup with a containment overpressure, the venting action will lower the pressure but it will release radioactivity to the environment. In order to reduce the radioactivity released, a filtered containment venting system (FCVS) can be used to retain iodine and aerosols radioactive releases coming from the containment atmosphere. However, during a SA, large quantities of hydrogen can also be generated. Hydrogen reacts violently with oxygen and its combustion could impair systems, components, or structures. For this reason, to protect the integrity of the FCVS against hydrogen explosions, an inertization system is found necessary. This system should create an inert atmosphere previous to any containment venting that impedes the contact of hydrogen and oxygen. In this paper, the inertization system for Cofrentes NPP is presented. It consists of a nitrogen injection located in three different points. A computational model of the FCVS as well as the inertization system has been created. The results show that if the nitrogen sweeps and the containment venting are properly synchronized, the hydrogen risk could be reduced to a minimum and therefore, the integrity of the FCVS would be preserved.
A Novel Approach for Ultrasound Guided Axillary Nerve Block: The Inferior Axilla Technique
Authors: Chang Ke-Vin , Lin Chih-Peng , Lin Chia-Shiang , Wu Wei-Ting , Özçakar Levent
Published: November 2017

.
Practical design of the electron gun for a microfocus x-ray source
Authors: Li W. P. , Wang P. F. , Liu J. B. , Zhao W. X. , Han L.
Published: November 2017

A practical electron gun including the cathode, the grid, the anode, the insulator, the joint flange, and the gun chamber was developed to build a 90 keV microfocus x-ray source with high performance. Based on the electron emission theory at metal surface, the cathode, the grid, and the anode were optimized to achieve fine crossover, high maximum brightness, and high effective brightness with 1 mA beam current. In order to improve stability of the gun, the grid, the anode, the insulator, the joint flange, and the gun chamber were designed and fabricated to eliminate discharge at the peak and the creepage along insulator. Results show that the effective brightness of this model is 1.05×105A/(cm2 sr) with 1 mA beam current, and the microfocus x-ray source has a resolution below 4 μm when the target current is 100 μA. The practical electron gun can improve the beam current quality of the microfocus x-ray source.
New Approaches and Therapeutic Options for Mycobacterium tuberculosis in a Dormant State
Authors: Caño-Muñiz Santiago , Anthony Richard , Niemann Stefan , Alffenaar Jan-Willem C.
Published: November 2017

We are far away from the days when tuberculosis (TB) accounted for 1 in 4 deaths during the 19th century. However,
Mycobacterium tuberculosis
complex (MTBC) strains are still the leading cause of morbidity and mortality by a single infectious disease, with 9.6 million cases and 1.5 million deaths reported. One-third of the world's population is estimated by the WHO to be infected with latent TB. During the last decade, several studies have aimed to define the characteristics of dormant bacteria in these latent infections. General features of the shift to a dormant state encompass several phenotypic changes that reduce metabolic activity. This low metabolic state is thought to increase the resistance of MTBC strains to host/environmental stresses, including antibiotic action. Once the stress ceases (e.g., interruption of treatment), dormant cells can reactivate and cause symptomatic disease again. Therefore, a proper understanding of dormancy could guide the rational development of new treatment regimens that target dormant cells, reducing later relapse. Here, we briefly summarize the latest data on the genetics involved in the regulation of dormancy and discuss new approaches to TB treatment.
Recombinant Endolysins as Potential Therapeutics against Antibiotic-Resistant Staphylococcus aureus: Current Status of Research and Novel Delivery Strategies
Authors: Haddad Kashani Hamed , Schmelcher Mathias , Sabzalipoor Hamed , Seyed Hosseini Elahe , Moniri Rezvan
Published: November 2017

Staphylococcus aureus
is one of the most common pathogens of humans and animals, where it frequently colonizes skin and mucosal membranes. It is of major clinical importance as a nosocomial pathogen and causative agent of a wide array of diseases. Multidrug-resistant strains have become increasingly prevalent and represent a leading cause of morbidity and mortality. For this reason, novel strategies to combat multidrug-resistant pathogens are urgently needed. Bacteriophage-derived enzymes, so-called endolysins, and other peptidoglycan hydrolases with the ability to disrupt cell walls represent possible alternatives to conventional antibiotics. These lytic enzymes confer a high degree of host specificity and could potentially replace or be utilized in combination with antibiotics, with the aim to specifically treat infections caused by Gram-positive drug-resistant bacterial pathogens such as methicillin-resistant
S. aureus
. LysK is one of the best-characterized endolysins with activity against multiple staphylococcal species. Various approaches to further enhance the antibacterial efficacy and applicability of endolysins have been demonstrated. These approaches include the construction of recombinant endolysin derivatives and the development of novel delivery strategies for various applications, such as the production of endolysins in lactic acid bacteria and their conjugation to nanoparticles. These novel strategies are a major focus of this review.
Pathogenesis, Humoral Immune Responses, and Transmission between Cohoused Animals in a Ferret Model of Human Respiratory Syncytial Virus Infection
Authors: Chan Kok Fei , Carolan Louise A. , Druce Julian , Chappell Keith , Watterson Daniel , Young Paul , Korenkov Daniil , Subbarao Kanta , Barr Ian G. , Laurie Karen L. , Reading Patrick C.
Published: November 2017

Small-animal models have been used to obtain many insights regarding the pathogenesis and immune responses induced following infection with human respiratory syncytial virus (hRSV). Among those described to date, infections in cotton rats, mice, guinea pigs, chinchillas, and Syrian hamsters with hRSV strains Long and/or A2 have been well characterized, although clinical isolates have also been examined. Ferrets are also susceptible to hRSV infection, but the pathogenesis and immune responses elicited following infection have not been well characterized. Here, we describe the infection of adult ferrets with hRSV Long or A2 via the intranasal route and characterized virus replication, as well as cytokine induction, in the upper and lower airways. Virus replication and cytokine induction during the acute phase of infection (days 0 to 15 postinfection) were similar between the two strains, and both elicited high levels of F glycoprotein-specific binding and neutralizing antibodies following virus clearance (days 16 to 22 postinfection). Importantly, we demonstrate transmission from experimentally infected donor ferrets to cohoused naive recipients and have characterized virus replication and cytokine induction in the upper airways of infected contact animals. Together, these studies provide a direct comparison of the pathogenesis of hRSV Long and A2 in ferrets and highlight the potential of this animal model to study serological responses and examine interventions that limit transmission of hRSV.

IMPORTANCE
Ferrets have been widely used to study pathogenesis, immunity, and transmission following human influenza virus infections; however, far less is known regarding the utility of the ferret model to study hRSV infections. Following intranasal infection of adult ferrets with the well-characterized Long or A2 strain of hRSV, we report virus replication and cytokine induction in the upper and lower airways, as well as the development of virus-specific humoral responses. Importantly, we demonstrate transmission of hRSV from experimentally infected donor ferrets to cohoused naive recipients. Together, these findings significantly enhance our understanding of the utility of the ferret as a small-animal model to investigate aspects of hRSV pathogenesis and immunity.
The Absence of DHHC3 Affects Primary and Latent Herpes Simplex Virus 1 Infection
Authors: Wang Shaohui , Mott Kevin R. , Cilluffo Marianne , Kilpatrick Casey L. , Murakami Shoko , Ljubimov Alexander V. , Kousoulas Konstantin G. , Awasthi Sita , Luscher Bernhard , Ghiasi Homayon
Published: November 2017

UL20, an essential herpes simplex virus 1 (HSV-1) protein, is involved in cytoplasmic envelopment of virions and virus egress. We reported recently that UL20 can bind to a host protein encoded by the zinc finger DHHC-type containing 3 (
ZDHHC3
) gene (also known as Golgi-specific DHHC zinc finger protein [GODZ]). Here, we show for the first time that HSV-1 replication is compromised in murine embryonic fibroblasts (MEFs) isolated from GODZ
−/−
mice. The absence of GODZ resulted in blocking palmitoylation of UL20 and altered localization and expression of UL20 and glycoprotein K (gK); the expression of gB and gC; and the localization and expression of tegument and capsid proteins within HSV-1-infected MEFs. Electron microscopy revealed that the absence of GODZ limited the maturation of virions at multiple steps and affected the localization of virus and endoplasmic reticulum morphology. Virus replication in the eyes of ocularly HSV-1-infected GODZ
−/−
mice was significantly lower than in HSV-1-infected wild-type (WT) mice. The levels of UL20, gK, and gB transcripts in the corneas of HSV-1-infected GODZ
−/−
mice on day 5 postinfection were markedly lower than in WT mice, whereas only UL20 transcripts were reduced in trigeminal ganglia (TG). In addition, HSV-1-infected GODZ
−/−
mice showed notably lower levels of corneal scarring, and HSV-1 latency reactivation was also reduced. Thus, normal HSV-1 infectivity and viral pathogenesis are critically dependent on GODZ-mediated palmitoylation of viral UL20.

IMPORTANCE
HSV-1 infection is widespread. Ocular infection can cause corneal blindness; however, approximately 70 to 90% of American adults exposed to the virus show no clinical symptoms. In this study, we show for the first time that the absence of a zinc finger protein called GODZ affects primary and latent infection, as well as reactivation, in ocularly infected mice. The reduced virus infectivity is due to the absence of the GODZ interaction with HSV-1 UL20. These results strongly suggest that binding of UL20 to GODZ promotes virus infectivity
in vitro
and viral pathogenesis
in vivo
.
Inflammasome Antagonism by Human Parainfluenza Virus Type 3 C Protein
Authors: Shil Niraj K. , Pokharel Swechha M. , Banerjee Amiya K. , Hoffman Michael , Bose Santanu
Published: November 2017

Human parainfluenza virus type 3 (HPIV3) is a negative-sense single-stranded RNA virus belonging to the
Paramyxoviridae
family. HPIV3 is a lung-tropic virus causing airway diseases, including pneumonia, croup, and bronchiolitis, during infancy and childhood. The activation of the inflammasome by pathogens results in the production of proinflammatory cytokines such as interleukin-1β (IL-1β) during infection. Thus, the inflammasome-mediated proinflammatory response plays a critical role in regulating the immune response and virus clearance. The inflammasome is a multimeric protein complex triggering caspase-1 activation. Activated caspase-1 cleaves pro-IL-1β into its mature (and active) secretory form. Our study revealed inflammasome activation in macrophages following HPIV3 infection. Specifically, the activation of the NLRP3/ASC inflammasome resulted in the production of mature IL-1β from HPIV3-infected cells. Furthermore, Toll-like receptor 2 (TLR2) activation (first signal) and potassium efflux (second signal) constituted two cellular events mediating inflammasome activation following HPIV3 infection. During our studies, we surprisingly identified the HPIV3 C protein as an antagonist of inflammasome activation. The HPIV3 C protein is an accessory protein encoded by the open reading frame of the viral phosphoprotein (P) gene. The HPIV3 C protein interacted with the NLRP3 protein and blocked inflammasome activation by promoting the proteasomal degradation of the NLRP3 protein. Thus, our studies report NLRP3/ASC inflammasome activation by HPIV3 via TLR2 signaling and potassium efflux. Furthermore, we have identified HPIV3 C as a viral component involved in antagonizing inflammasome activation.

IMPORTANCE
Human parainfluenza virus type 3 (HPIV3) is a paramyxovirus that causes respiratory tract diseases during infancy and childhood. Currently, there is no effective vaccine or antiviral therapy for HPIV3. Therefore, in order to develop anti-HPIV3 agents (therapeutics and vaccines), it is important to study the HPIV3-host interaction during the immune response. Inflammasomes play an important role in the immune response. Inflammasome activation by HPIV3 has not been previously reported. Our studies demonstrated inflammasome activation by HPIV3 in macrophages. Specifically, HPIV3 activated the NLRP3/ASC inflammasome by TLR2 activation and potassium efflux. C proteins of paramyxoviruses are accessory proteins encoded by the viral phosphoprotein gene. The role of the C protein in inflammasome regulation was unknown. Surprisingly, our studies revealed that the HPIV3 C protein antagonizes inflammasome activation. In addition, we highlighted for the first time a mechanism utilized by paramyxovirus accessory proteins to block inflammasome activation. The HPIV3 C protein interacted with the NLRP3 protein to trigger the proteasomal degradation of the NLRP3 protein.
Recipient-Biased Competition for an Intracellularly Generated Cross-Fed Nutrient Is Required for Coexistence of Microbial Mutualists
Authors: McCully Alexandra L. , LaSarre Breah , McKinlay James B.
Published: November 2017

Many mutualistic microbial relationships are based on nutrient cross-feeding. Traditionally, cross-feeding is viewed as being unidirectional, from the producer to the recipient. This is likely true when a producer’s waste, such as a fermentation product, has value only for a recipient. However, in some cases the cross-fed nutrient holds value for both the producer and the recipient. In such cases, there is potential for nutrient reacquisition by producer cells in a population, leading to competition against recipients. Here, we investigated the consequences of interpartner competition for cross-fed nutrients on mutualism dynamics by using an anaerobic coculture pairing fermentative
Escherichia coli
and phototrophic
Rhodopseudomonas palustris
. In this coculture,
E. coli
excretes waste organic acids that provide a carbon source for
R. palustris
. In return,
R. palustris
cross-feeds
E. coli
ammonium (NH
4
+
), a compound that both species value. To explore the potential for interpartner competition, we first used a kinetic model to simulate cocultures with varied affinities for NH
4
+
in each species. The model predicted that interpartner competition for NH
4
+
could profoundly impact population dynamics. We then experimentally tested the predictions by culturing mutants lacking NH
4
+
transporters in both NH
4
+
competition assays and mutualistic cocultures. Both theoretical and experimental results indicated that the recipient must have a competitive advantage in acquiring cross-fed NH
4
+
to sustain the mutualism. This recipient-biased competitive advantage is predicted to be crucial, particularly when the communally valuable nutrient is generated intracellularly. Thus, the very metabolites that form the basis for mutualistic cross-feeding can also be subject to competition between mutualistic partners.

IMPORTANCE
Mutualistic relationships, particularly those based on nutrient cross-feeding, promote stability of diverse ecosystems and drive global biogeochemical cycles. Cross-fed nutrients within these systems can be either waste products valued by only one partner or nutrients valued by both partners. Here, we explored how interpartner competition for a communally valuable cross-fed nutrient impacts mutualism dynamics. We discovered that mutualism stability necessitates that the recipient have a competitive advantage against the producer in obtaining the cross-fed nutrient, provided that the nutrient is generated intracellularly. We propose that the requirement for recipient-biased competition is a general rule for mutualistic coexistence based on the transfer of intracellularly generated, communally valuable resources.
Use of humour in medical education: a survey of students and teachers at a medical school in China
Authors: Liu Yan-Ping , Sun Lei , Wu Xiao-Fen , Yang Yi , Zhang Cun-Tai , Zhou Hong-Lian , Quan Xiao-Qing
Published: November 2017

Objective

Humour is a powerful resource in medical education. The purpose of this study is to investigate what students and teachers think about the use of humour. What challenges do teachers face in using humour and how they address them are also the subject of the present study.

Design

Separate cross-sectional questionnaire surveys.

Setting

Tongji Medical College and Tongji Hospital in China.

Participants

327 students at Tongji Medical College and 165 physician teachers at Tongji Hospital in China.

Main outcome measures

The primary study outcome was assessed by proportion.

Results

87% of student and teacher respondents agreed with using humour in the didactic setting. They felt humour fostered a positive didactic atmosphere. Interesting clinical case was the most frequently used humour type by teachers and considered the most effective by students. Lack of humorous materials related to the lecture subject was the main challenge to humour use cited by teachers. Collecting humorous materials in teacher’s daily work and life, observing teachers with a reputation for successfully using humour, and efficiently using the internet-enhanced humour use ability.

Conclusion

The present study confirms that most medical students and physician teachers support the use of humour in medical didactics, with particular strategies aiding its use and positive impact.
Surgical academic reach: the higher degree effect quantified
Authors: Brown Chris , Abdelrahman Tarig , Thomas Charlotte , Pollitt John , Lewis Wyn G
Published: November 2017

Introduction

Proof of professional specific academic attainment is embedded within the Joint Committee on Surgical Training 2013 general surgery curriculum, mandating that all higher general surgical trainees (HST) obtain three peer-reviewed publications to qualify for Certification of Completion of Training. Yet, Modernising Medical Careers (MMC) has been associated with a trend away from the gold standard postgraduate credentials of higher degrees by research. This study aimed to evaluate the academic achievements of a post-MMC UK Deanery HST cohort to determine what additional benefits higher degree study might confer.

Method

The Scopus bibliographic database (Elsevier, RELX Group) was used to characterise the academic profiles of 101 consecutive HSTs and supplemented with Intercollegiate Surgical Programme Curriculum data. Primary outcome measures were numbers of publications, citations and Hirsch indices (HI).

Results

Thirty-seven HSTs (36.6%) had been awarded higher degrees (29 Doctor of Medicine, 8 Doctor of Philosophy). Academic profiles of HSTs with higher degrees were stronger than those of HSTs without, specifically: median (range) publication numbers 16 (2–57) vs 2 (0–11, P<0.001), citations 93 (0–1600) vs 6 (0–132, P<0.001), first author publications 6 (0–33) vs 3 (0–106, P<0.001), communications to learnt societies 30 (5–79) vs 8 (2–35, P<0.001) and HI 6 (1–26) vs 1 (0–6, P<0.001).

Conclusion

Proof of academic reach by higher degree was associated with important enhanced professional credentials, strengthening HIs sixfold. Trainers and trainees alike should be aware of the relative magnitude of such benefits when planning educational programmes.
CREDIT CARD ADOPTION AND USAGE IN CHINA: URBAN–RURAL COMPARISONS
Authors: PORTO NILTON , HUANG YU , XIAO JING JIAN
Published: November 2017

This study examines the differences in credit card behaviors between rural and urban households in China. Using data from a national survey of Chinese households, results show distinct differences between rural and urban respondents in credit card adoption and usage even after controlling for relevant demographic, financial, attitude, and expectation variables. Rural households are less likely to possess a credit card, possibly due to supply side limitations such as lack of financial institutions and low rate of credit card acceptance in rural areas. No urban–rural difference is found in credit card payment behavior. Implications for policymakers and credit card issuers are discussed.