bluuebunny/crossref_metadata_2025 huggingface dataset:
Causal Change Detection in Possibly Integrated Systems: Revisiting the Money–Income Relationship*
Authors: Shi Shuping , Hurn Stan , Phillips Peter C B
Published: February 2019

This paper re-examines changes in the causal link between money and income in the United States over the past half century (1959–2014). Three methods for the data-driven discovery of change points in causal relationships are proposed, all of which can be implemented without prior detrending of the data. These methods are a forward recursive algorithm, a rolling window algorithm, and a recursive evolving algorithm all of which utilize subsample tests of Granger causality within a lag-augmented vector autoregressive framework. The limit distributions for these subsample Wald tests are provided. Bootstrap methods are developed to control family-wise size in the implementation of the recursive testing algorithms. The results from a suite of simulation experiments suggest that the recursive evolving window algorithm provides the most reliable results, followed by the rolling window method. The forward expanding window procedure is shown to have the worst performance. Both the rolling window and recursive evolving approaches find evidence of Granger causality running from money to income during the Volcker period in the 1980s. The forward algorithm does not find any evidence of causality over the entire sample period.
Discovery of a putative supernova remnant around the long-period X-ray pulsar SXP 1323 in the Small Magellanic Cloud
Authors: Gvaramadze V V , Kniazev A Y , Oskinova L M
Published: February 2019

We report the discovery of a circular shell centred on the Be X-ray binary (BeXB) SXP 1323 in the Small Magellanic Cloud. The shell was detected in an H α image obtained with the Very Large Telescope. Follow-up spectroscopy with the Southern African Large Telescope showed that the shell expands with a velocity of ${\approx }100{\rm \, km\, s^{-1}}$ and that its emission is due to shock excitation. We suggest that this shell is a remnant of the supernova explosion that led to the formation of SXP 1323’s neutron star ${\approx }40\, 000$ yr ago. SXP 1323 represents the second known case of a BeXB associated with a supernova remnant (the first one is SXP 1062). Interestingly, both of these BeXBs harbour long-period pulsars and are located in a low-metallicity galaxy.
Defining the Therapeutic Singing Voice: An Analysis of Four Music Therapists’ Clinical Work
Authors: Bingham Martina C
Published: February 2019

The purpose of this study was to examine the ways music therapists use their singing voices in music therapy sessions and, in doing so, to provide a working definition of the therapeutic singing voice. Four music therapists were observed leading at least 10 music therapy sessions each in order to examine the ways they used their singing voices in clinical practice. Interviews with each of these therapists, at the completion of session observations, enriched these observational data. Data were analyzed in two stages. First, individual singing voice profiles were developed for each music therapist, and second, these profiles were integrated to define essential singing voice characteristics. These characteristics included flexible postures and physicality, diverse breathing methods and strategies of phonation, flexible resonance strategies, improvisational skills, and knowledge of diverse music genres. Implications for vocal education and training in music therapy programs are discussed.
The divergent logics of industrial change: a comparison of export-cheese processors in Nicaragua
Authors: Fuentes Alberto
Published: February 2019

According to the industrial policy literature, market failures hamper industrialization processes among private sector firms. Its proposed state-centered solution builds on a conception of these firms as solely profit-maximizing and largely unable to independently solve collection action dilemmas. This article offers a more nuanced portrayal of the private sector’s behavior. It draws upon a broad comparative institutional literature on embedded capitalism and an empirical study of the unexpected industrial transformation of cheese processors in rural Nicaragua to claim that nonmarket logics, such as the familial or community logics, may similarly impinge upon firm action. These logics endow firms with contrasting understandings of group boundaries, on the one hand, and organizational priorities and associated governance mechanisms, on the other—two factors that, together, produce divergent, and often effective, responses to collective action dilemmas. The article concludes with a review of the argument’s implications for industrial policy.
Drug diversion detection
Authors: Perry Jason C. , Vandenhouten Christine L.
Published: February 2019

Software offers real-time data for prompt identification and assistance
Our finalist Emily Emma
Authors: Mulligan Marie
Published: February 2019

The following manuscript is the runner-up entry submitted to Nursing Management for the 2018 Richard Hader Visionary Leader Award in recognition of Emily Emma, DNP, RN-BC, NEA-BC, ONC, nurse manager of the orthopedic-telemetry and progressive care units at Mather Hospital in Long Island, N.Y. Emily was formally recognized as the runner-up for the award, sponsored by Hackensack Meridian Health, before the Keynote Address on September 26 at Congress2018 in Lake Buena Vista, Fla.
Peripartum Cardiomyopathy
Authors: Cunningham F. Gary , Byrne John J. , Nelson David B.
Published: February 2019

Peripartum cardiomyopathy is defined by left ventricular dysfunction and development of cardiac failure without a known cause and occurring in the final month of pregnancy and up to 5 months postpartum. Peripartum cardiomyopathy is an important and steadily increasing cause of pregnancy-associated morbidity and mortality. The incidence of peripartum cardiomyopathy in the United States has been estimated recently as 1 in 2,230 births and approximately 1 in 1,000 births worldwide. The etiopathogenesis of peripartum cardiomyopathy remains elusive; however, it is generally thought to be from a two-hit hypothesis in which an underlying cardiomyocyte protein mutation results in apoptosis mediated by vascular and hormonal actions. Clinical recognition is integral to the management of this disease, because there must be careful exclusion of alternative etiologies. Although there are no disease-specific therapies, management of peripartum cardiomyopathy is based on treatment of heart failure and its symptoms, repressing neurohormonal responses, and preventing long-term sequelae. Ventricular function recovery and rates of recurrence of peripartum cardiomyopathy vary by ethnicity and geography. Mortality rates associated with peripartum cardiomyopathy range from 3% to 40%, depending on geographic location. In this review, normal cardiovascular adaptations in pregnancy are summarized and current evidence-based clinical management of the disease is discussed.
Description of Sphingomonas mesophila sp. nov., isolated from Gastrodia elata Blume
Authors: Li Yan-Qiong , Narsing Rao Manik Prabhu , Zhang Hui , Guo Yan-Mei , Dong Zhou-Yan , Alkhalifah Dalal Hussien M. , Hozzein Wael N. , Xiao Min , Li Wen-Jun
Published: February 2019

A Gram-staining-negative, strictly aerobic, non-motile strain, SYSUP0001T, was isolated from tubers of Gastrodia elata Blume. The 16S rRNA gene sequence result indicated that SYSUP0001T represents a member of the genus

Sphingomonas

, with the highest sequence similarity (97.7 %) to the type strain of

Sphingomonas

ginsengisoli

. SYSUP0001T grew at 14–37 °C and pH 6–8, with optimum growth at 28 °C and pH 7. Tolerance to NaCl was up to 3 % (w/v) with optimum growth in the absence of NaCl. The respiratory quinone was Q-10. The major fatty acids were C18 : 1ω7c, Summed feature 3 (C16 : 1ω7c/C16 : 1ω6c), and C16 : 0. The polar lipids were diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), sphingoglycolipid (SGL), phosphatidylcholine (PC) and four unidentified polar lipids (L). The DNA G+C content was 67.5 %. The average nucleotide identity (ANI) values between SYSUP0001T and closely related members of the genus

Sphingomonas

were below the cut-off level (95–96 %) for species delineation. On the basis of the phenotypic, phylogenetic and chemotaxonomic characterizations, SYSUP0001T represents a novel species of the genus

Sphingomonas

, for which the name

Sphingomonasmesophila
sp. nov. is proposed. The type strain is SYSUP0001T (=KCTC 62179 T=CGMCC 1.16462T).
Desulfovibrio gilichinskyi sp. nov., a cold-adapted sulfate-reducing bacterium from a Yamal Peninsula cryopeg
Authors: Ryzhmanova Yana , Abashina Tatyana , Petrova Daria , Shcherbakova Viktoria
Published: February 2019

A psychrotolerant non-spore-forming sulfate-reducing bacterium, strain K3ST, was isolated from a Yamal Peninsula cryopeg within permafrost. Strain K3STgrew at subzero temperatures and required Na+for growth. The new bacterium was able to use lactate, formate, pyruvate, fumarate, alanine, ethanol and molecular hydrogen as electron donors in the presence of sulfate, and used sulfate, sulfite, thiosulfate and elemental sulfur as electron acceptors in the presence of lactate. Fe(III)-citrate and Fe(III)-EDTA were reduced without visible growth. Major polar lipids were рhosphatidylserine, рhosphatidylethanolamine, phospholipids, cardiolipin and aminolipid; major cellular fatty acids were C16 : 1ω7, C16 : 0and C18 : 1ω7; and the predominant isoprenoid quinone was MK-6 (H2). The genomic DNA G+C content was found to be 42.33 mol%. Phylogenetic analysis showed that the closest relative of the new isolate wasDesulfovibrio ferrireducensstrain 61Twith 97.1 % 16S rRNA gene similarity. In addition, the ANI value between strain K3STandD. ferrireducens61Twas 82.1 %. On the basis of the genomic and polyphasic taxonomy data of strain K3ST, we conclude that the strain is a representative of a novel speciesDesulfovibriogilichinskyisp. nov. (=VKM B-2877T=DSM 100341T).
Arenaviridae exoribonuclease presents genomic RNA edition capacity
Authors: Yekwa Elsie , Aphibanthammakit Chutima , Carnec Xavier , Coutard Bruno , Picard Caroline , Canard Bruno , Baize Sylvain , Ferron François
Published: February 2019

The Arenaviridae is a large family of viruses causing both acute and persistent infections and causing significant public health concerns in afflicted regions. A “trademark” of infection is the quick and efficient immuno-suppression mediated in part by a 3’-5’ RNA exonuclease domain (ExoN) of the Nucleoprotein (NP). Mopeia virus, the eastern African counterpart of Lassa virus, carries such ExoN domain, but does not suppress the host innate immunity. We have recently reported the crystal structure of the Mopeia virus ExoN domain, which presents a conserved fold and active site. In the present study, we show that the ExoN activity rules out a direct link between ExoN activity and alteration of the host innate immunity. We found that the Arenavirus ExoN, however, is able to excise mis-incorporated bases present at the 3’-end of double stranded RNA. ExoN(-) arenaviruses cultured in cells dampened in innate immunity still replicated in spite of a significant reduction in the viral charge over several passages. The remaining ExoN(-) virus population showed an increased base substitution rate on a narrow nucleotide spectrum, linking the ExoN activity to genome editing. Since, the Arenavirus ExoN belongs to the same nuclease family as that of the nsp14 coronavirus ExoN ; which has been recently shown to promote viral RNA synthesis proofreading; we propose that Arenavirus ExoN is involved in a “limited RNA editing” mechanism mainly controlled by structural constraints and a low mutational/fitness ratio.

Author summary

Only Arenaviridae and Coronaviridae encode a 3’-5’ RNA exonuclease domain (ExoN) in their genome. This activity is either used to counteract the innate immunity response during viral infection or to ensure genome stability during replication. Mopeia virus (MOPV), the eastern African counterpart of Lassa virus, carries such ExoN domain, but does not suppress the host innate immunity. We studied MOPV ExoN activity both in vitro and in cellula to assess the role of ExoN MOPV and found that the Arenaviral ExoN is fully active on dsRNA, and is able like the one of Coronaviridae to excise a mismatched base. We measured genetic stability and found evidence of a limited spectrum of RNA synthesis proofreading mechanism, together with a strongly impacted viral replication. We propose that the Arenaviral ExoN is involved in a functional check of the conserved RNA structures of the viral genome.
Socioeconomic inequality in recent adverse mortality trends in Scotland
Authors: Fenton Lynda , Wyper Grant , McCartney Gerry , Minton Jon
Published: February 2019

Structured Abstract

Background

Gains in life expectancies have stalled in Scotland, as in several other countries, since around 2012. The relationship between stalling mortality improvements and socioeconomic inequalities in health is unclear.

Methods

We calculate the percentage improvement in age-standardised mortality rates (ASMR) in Scotland overall, by sex, and by Scottish Index of Multiple Deprivation (SIMD) quintile and gender, for two periods: 2006-2011 and 2012-2017. We then calculate the socioeconomic gradient in improvements for both periods.

Results

Between 2006 and 2011, ASMRs fell by 10.6% (10.1% in females; 11.8% in males), but between 2012 and 2017 ASMRs only fell by 2.6% (3.5% in females; 2.0% in males). The socioeconomic gradient in ASMR improvement more than quadrupled, from 0.4% per quintile in 2006-2011 (0.7% in females; 0.6% in males) to 1.7% (2.0% in females; 1.4% in males). Within the most deprived quintile, ASMRs fell in the 2006-2011 period (8.6% overall; 7.2% in females; 9.8% in males), but rose in the 2012-2017 period (by 1.5% overall; 0.7% in females; 2.1% in males).

Conclusion

As mortality improvements in Scotland stalled in 2012-2017, socioeconomic gradients in mortality became steeper, with increased mortality rates over this period in the most socioeconomically deprived fifth of the population.

What we already know

Improvements in mortality rates slowed markedly around 2012 in Scotland and a number of other high-income countries.

Scotland has large socioeconomic health inequalities, and the absolute gap in premature mortality between most and least deprived has increased since 2013.

The relationship between stalling mortality improvements and socioeconomic inequalities in health is unclear.

What this study adds

Stalling in mortality improvement has occurred across the whole population of Scotland, but is most acute in the most socioeconomically deprived areas.

Mortality improvements went into reverse (i.e. deteriorated) in the most deprived fifth of areas between 2012 and 2017.

Research to further characterise and explain recent aggregate trends should incorporate consideration of the importance of socioeconomic inequalities within proposed explanations.
Environmental morphing enables informed dispersal of the dandelion diaspore
Authors: Seale Madeleine , Zhdanov Oleksandr , Soons Merel B. , Cummins Cathal , Kroll Erika , Blatt Michael R. , Zare-Behtash Hossein , Busse Angela , Mastropaolo Enrico , Bullock James M. , Viola Ignazio Maria , Nakayama Naomi
Published: February 2019

Animal migration is highly sensitised to environmental cues, but plant dispersal is considered largely passive. The common dandelion, Taraxacum officinale, bears an intricate haired pappus facilitating flight. The pappus enables the formation of a separated vortex ring during flight; however, the pappus structure is not static but reversibly changes shape by closing in response to moisture. We hypothesised that this leads to changed dispersal properties in response to environmental conditions. Using wind tunnel experiments for flow visualisation, particle image velocimetry, and flight tests we characterised the fluid mechanics effects of the pappus morphing. We also modelled dispersal to understand the impact of pappus morphing on diaspore distribution. Pappus morphing dramatically alters the fluid mechanics of diaspore flight. We found that when the pappus closes in moist conditions, the drag coefficient decreases and thus the falling velocity is greatly increased. Detachment of diaspores from the parent plant also substantially decreases. The change in detachment when the pappus closes increases dispersal distances by reducing diaspore release when wind speeds are low. We propose that moisture-dependent pappus-morphing is a form of informed dispersal allowing rapid responses to changing conditions.
Predictability in the evolution of Orthopteran cardenolide insensitivity
Authors: Yang Lu , Ravikanthachari Nitin , Mariño-Pérez Ricardo , Deshmukh Riddhi , Wu Mariana , Rosenstein Adam , Kunte Krushnamegh , Song Hojun , Andolfatto Peter
Published: February 2019

The repeated evolutionary specialisation of distantly related insects to cardenolide-containing host plants provides a stunning example of parallel adaptation. Hundreds of herbivorous insect species have independently evolved insensitivity to cardenolides, which are potent inhibitors of the alpha-subunit of Na+, K+-ATPase (ATPα). Previous studies investigating ATPα-mediated cardenolide insensitivity in five insect orders have revealed remarkably high levels of parallelism in the evolution of this trait, including the frequent occurrence of parallel amino acid substitutions at two sites and recurrent episodes of duplication followed by neo-functionalisation. Here we add data for a sixth insect order, Orthoptera, which includes an ancient group of highly aposematic cardenolide-sequestering grasshoppers in the family Pyrgomorphidae. We find that Orthopterans exhibit largely predictable patterns of evolution of insensitivity established by sampling other insect orders. Taken together the data lend further support to the proposal that negative pleiotropic constraints are a key determinant in the evolution of cardenolide insensitivity in insects. Furthermore, analysis of our expanded taxonomic survey implicates positive selection acting on site 111 of cardenolide-sequestering species with a single-copy of ATPα, and sites 115, 118 and 122 in lineages with neo-functionalised duplicate copies, all of which are sites of frequent parallel amino acid substitution.
Cell wall integrity signaling regulates cell wall regeneration via transcriptional activation inChlamydomonas reinhardtii
Authors: Cronmiller Evan , Toor Deepak , Shao Nai Chun , Kariyawasam Thamali , Wang Ming Hsiu , Lee Jae-Hyeok
Published: February 2019

An intact cell wall is critical for protecting the cell from osmotic challenges and harmful environments. Signaling mechanisms are necessary to monitor cell wall integrity and to regulate cell wall production and remodeling during growth and division cycles. The green alga,Chlamydomonas, has a proteinaceous cell wall of defined structure that is readily removed by gametolysin (g-lysin), a metalloprotease released during sexual mating. Naked cells treated with g-lysin induce the mRNA accumulation of > 100 cell wall-related genes within an hour, offering a system to study signaling and regulatory mechanisms forde novocell wall assembly. Combining quantitative RT-PCR and luciferase reporter assays to probe transcript accumulation and promoter activity, we revealed that up to 500-fold upregulation of cell wall-related genes was driven at least partly by transcriptional activation upon g-lysin treatment. To investigate how naked cells trigger this rapid transcriptional activation, we tested whether osmotic stress and cell wall integrity are involved in this process. Under a constant hypotonic condition, comparable levels of cell wall-gene activation were observed by g-lysin treatment. In contrast, cells in an iso- or hypertonic condition showed up to 80% reduction in the g-lysin-induced gene activation, suggesting that hypotonic conditions are required for full-scale responses to g-lysin treatment. To test whether mechanical perturbation is involved, we isolated and examined a new set of cell wall mutants with defective or little cell walls. All cell wall mutants examined showed a constitutive upregulation of cell wall-related genes at the level, which would only be achieved by the g-lysin treatment in wild-type cells. Our study suggests a signaling that monitors mechanical defects of cell walls and regulates cell wall-gene expression inChlamydomonas, which may relate to cell wall integrity signaling mechanisms in plants.
Insulin-stimulated glucose uptake partly relies on p21-activated kinase (PAK)-2, but not PAK1, in mouse skeletal muscle
Authors: Møller Lisbeth L. V. , Jaurji Merna , Kjøbsted Rasmus , Joseph Giselle A. , Madsen Agnete B. , Knudsen Jonas R. , Lundsgaard Annemarie , Andersen Nicoline R. , Schjerling Peter , Jensen Thomas E. , Krauss Robert S. , Richter Erik A. , Sylow Lykke
Published: February 2019

Objective

Skeletal muscle glucose uptake is essential for maintaining whole-body glucose homeostasis and accounts for the majority of glucose disposal in response to insulin. The group I p21-activated kinase (PAK) isoforms PAK1 and PAK2 are activated in response to insulin in skeletal muscle. Interestingly, PAK1/2 signalling is impaired in insulin-resistant mouse and human skeletal muscle and PAK1 has been suggested to be required for insulin-stimulated GLUT4 translocation. However, the relative contribution of PAK1 and PAK2 to insulin-stimulated glucose uptake in mature skeletal muscle is unresolved. The aim of the present investigation was to determine the requirement for PAK1 and PAK2 in whole-body glucose homeostasis and insulin-stimulated glucose uptake in skeletal muscle.

Methods

Glucose uptake was measured in isolated skeletal muscle incubated with a pharmacological inhibitor (IPA-3) of group I PAKs and in muscle from whole-body PAK1 knockout (KO), muscle-specific PAK2 (m)KO and double whole-body PAK1 and muscle-specific PAK2 knockout mice.

Results

The whole-body respiratory exchange ratio was largely unaffected by lack of PAK1 and/or PAK2. Whole-body glucose tolerance was mildly impaired in PAK2 mKO, but not PAK1 KO mice. IPA-3 partially reduced (−20%) insulin-stimulated glucose uptake in mouse soleus muscle. In contrast to a previous study of GLUT4 translocation in PAK1 KO mice, PAK1 KO muscles displayed normal insulin-stimulated glucose uptake in vivo and in isolated muscle. On the contrary, glucose uptake was slightly reduced in response to insulin in glycolytic extensor digitorum longus muscle lacking PAK2, alone (−18%) or in combination with PAK1 KO (−12%).

Conclusions

Insulin-stimulated glucose uptake partly relies on PAK2, but not PAK1, in mouse skeletal muscle. Thus, the present study challenges that group I PAKs, and especially PAK1, are major regulators of whole-body glucose homeostasis and insulin-stimulated glucose uptake in skeletal muscle.
Deciphering the interstrand crosslink DNA repair network expressed byTrypanosoma brucei
Authors: Dattani Ambika , Wilkinson Shane
Published: February 2019

Interstrand 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 summary

Parasites 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

Photorhabdus 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

Many 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 Summary

Recombinant 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.
Comprehensive, integrated, and phased whole-genome analysis of the primary ENCODE cell line K562
Authors: Zhou Bo , Ho Steve S. , Greer Stephanie U. , Zhu Xiaowei , Bell John M. , Arthur Joseph G. , Spies Noah , Zhang Xianglong , Byeon Seunggyu , Pattni Reenal , Ben-Efraim Noa , Haney Michael S. , Haraksingh Rajini R. , Song Giltae , Ji Hanlee P. , Perrin Dimitri , Wong Wing H. , Abyzov Alexej , Urban Alexander E.
Published: February 2019

K562 is widely used in biomedical research. It is one of three tier-one cell lines of ENCODE and also most commonly used for large-scale CRISPR/Cas9 screens. Although its functional genomic and epigenomic characteristics have been extensively studied, its genome sequence and genomic structural features have never been comprehensively analyzed. Such information is essential for the correct interpretation and understanding of the vast troves of existing functional genomics and epigenomics data for K562. We performed and integrated deep-coverage whole-genome (short-insert), mate-pair, and linked-read sequencing as well as karyotyping and array CGH analysis to identify a wide spectrum of genome characteristics in K562: copy numbers (CN) of aneuploid chromosome segments at high-resolution, SNVs and indels (both corrected for CN in aneuploid regions), loss of heterozygosity, megabase-scale phased haplotypes often spanning entire chromosome arms, structural variants (SVs), including small and large-scale complex SVs and nonreference retrotransposon insertions. Many SVs were phased, assembled, and experimentally validated. We identified multiple allele-specific deletions and duplications within the tumor suppressor gene FHIT. Taking aneuploidy into account, we reanalyzed K562 RNA-seq and whole-genome bisulfite sequencing data for allele-specific expression and allele-specific DNA methylation. We also show examples of how deeper insights into regulatory complexity are gained by integrating genomic variant information and structural context with functional genomics and epigenomics data. Furthermore, using K562 haplotype information, we produced an allele-specific CRISPR targeting map. This comprehensive whole-genome analysis serves as a resource for future studies that utilize K562 as well as a framework for the analysis of other cancer genomes.
Crystal structures of two nickel(II) macrocyclic salts: (5,7,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane)nickel(II) bis(perchlorate) monohydrate and (5,7,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane)nickel(II) dibromide trihydrate
Authors: Corfield Peter W. R. , Goedken Virgil L.
Published: February 2019

The crystal structure of the Ni-14 macrocycle salt, (5,7,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane)nickel(II) bis(perchlorate) hemihydrate, [Ni(C16H36N4)]2(ClO4)4·H2O, contains two different diasteriomeric macrocyclic cations in the asymmetric unit, one with two NH protons on each side of the cation (Ia), and the other with all four NH protons on the same side (Ib). The crystal structure of the bromide trihydrate salt of the same Ni-14 macrocyclic cation, namely (5,7,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane)nickel(II) dibromide trihydrate, [Ni(C16H36N4)]Br2·3H2O (II), contains only the same diastereomer as Ib, with the four N—H bonds on the same side. The geometry around the Ni atom differs slightly between the two diastereomeric cations, as the mean Ni—N distance in Ia is 1.952 (2) Å, while that for Ib and II is 1.928 (2) Å. The hexamethyl substitution in all three macrocyclic cations has the two dimethyl-substituted C atoms cis to one another, different from the trans 5,5,7,12,12,14-hexamethyl Ni-14 cations found in all but one of the many published crystal structures of hexamethyl Ni-14 macrocycles. In each of the two crystal structures, the anions, water molecules, and N—H protons of the macrocyclic cations form extensive hydrogen-bonded zigzag chains propagating along [001] in I and [010] in II.
Potassium bis(2-methyllactato)borate hemihydrate
Authors: Gokila Govindharajan , Thiruvalluvar Aravazhi Amalan , Ramachandra Raja Chidambaram
Published: February 2019

The asymmetric unit of the title organic–inorganic hybrid salt poly[aquabis[μ3-bis(2-methyllactato)borato]dipotassium], [K(C8H12BO6)(H2O)0.5]
n
, consists of one bis(2-methyllactato)borate anion, one potassium cation and one water molecule that shows half occupancy due to disorder around a twofold rotation axis. The potassium cation is pseudo-octahedrally coordinated by five O atoms of four symmetry-related bis(2-methyllactato)borate ligands and by the half-occupied water molecule. O—H...O hydrogen bonds between the water molecule and one of the borate O atoms of the bis(2-methyllactato)borate ligand are present in the crystal structure.
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

Purpose

The 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/approach

This 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.

Findings

The 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/value

The 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

Purpose

This 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/approach

An 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.

Findings

This 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 implications

This 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/value

Although 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

The 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

The 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

Fatal 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

Mandibular 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

We 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

Effective 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.