bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimal Longevity Hedging Framework for Insurance Companies Considering Basis and Mispricing Risks
Authors: Yang Sharon S. , Huang Hong‐Chih , Yeh Yu‐Yun 
Published: February 2018

AbstractThis article studies the optimal hedging strategy to deal with longevity risk for the life insurer considering basis risk. We build up a longevity hedging framework that incorporates not only the internal natural hedging but also the external hedging by using the q‐forwards. The optimal hedging strategy is obtained by a minimizing‐variance approach that can minimize the impact of longevity risk on the insurer's profit function. To investigate the basis risk, instead of using population mortality, we adopt a unique mortality data set of annuity and life insurance policies that enable us to calibrate the multi‐population mortality dynamics for different lines of insurance policies. We consider three different hedging strategies: the natural hedging strategy, the external hedging strategy, and combining both natural hedging, and external hedging strategies. The hedge effectiveness for different hedging strategies is evaluated. In addition, the mortality forecast model based on VECM and ARIMA are used to examine the impact of basis risk on hedge effectiveness. As a result, combining both internal and external hedging strategies is the most effective way to manage longevity risk. Ignoring the basis risk will decrease the hedge effectiveness.
The characteristic function of rough Heston models
Authors: El Euch Omar , Rosenbaum Mathieu 
Published: February 2018

AbstractIt has been recently shown that rough volatility models, where the volatility is driven by a fractional Brownian motion with small Hurst parameter, provide very relevant dynamics in order to reproduce the behavior of both historical and implied volatilities. However, due to the non‐Markovian nature of the fractional Brownian motion, they raise new issues when it comes to derivatives pricing. Using an original link between nearly unstable Hawkes processes and fractional volatility models, we compute the characteristic function of the log‐price in rough Heston models. In the classical Heston model, the characteristic function is expressed in terms of the solution of a Riccati equation. Here, we show that rough Heston models exhibit quite a similar structure, the Riccati equation being replaced by a fractional Riccati equation.
Reductions in complexity of mitochondrial genomes in lichen‐forming fungi shed light on genome architecture of obligate symbioses
Authors: Pogoda Cloe S. , Keepers Kyle G. , Lendemer James C. , Kane Nolan C. , Tripp Erin A. 
Published: February 2018

AbstractSymbioses among co‐evolving taxa are often marked by genome reductions such as a loss of protein‐coding genes in at least one of the partners as a means of reducing redundancy or intergenomic conflict. To explore this phenomenon in an iconic yet under‐studied group of obligate symbiotic organisms, mitochondrial genomes of 22 newly sequenced and annotated species of lichenized fungi were compared to 167 mitochondrial genomes of nonlichenized fungi. Our results demonstrate the first broad‐scale loss of atp9 from mitochondria of lichenized fungi. Despite key functions in mitochondrial energy production, we show that atp9 has been independently lost in three different lineages spanning 10 of the 22 studied species. A search for predicted, functional copies of atp9 among genomes of other symbionts involved in each lichen revealed the full‐length, presumably functional copies of atp9 in either the photosynthetic algal partner or in other symbiotic fungi in all 10 instances. Together, these data yield evidence of an obligate symbiotic relationship in which core genomic processes have been streamlined, likely due to co‐evolution.
Seascape genomics reveals adaptive divergence in a connected and commercially important mollusc, the greenlip abalone (Haliotis laevigata), along a longitudinal environmental gradient
Authors: Sandoval‐Castillo Jonathan , Robinson Nick A. , Hart Anthony M. , Strain Lachlan W. S. , Beheregaray Luciano B. 
Published: February 2018

AbstractPopulations of broadcast spawning marine organisms often have large sizes and are exposed to reduced genetic drift. Under such scenarios, strong selection associated with spatial environmental heterogeneity is expected to drive localized adaptive divergence, even in the face of connectivity. We tested this hypothesis using a seascape genomics approach in the commercially important greenlip abalone (Haliotis laevigata). We assessed how its population structure has been influenced by environmental heterogeneity along a zonal coastal boundary in southern Australia linked by strong oceanographic connectivity. Our data sets include 9,109 filtered SNPs for 371 abalones from 13 localities and environmental mapping across ~800 km. Genotype–environment association analyses and outlier tests defined 8,786 putatively neutral and 323 candidate adaptive loci. From a neutral perspective, the species is better represented by a metapopulation with very low differentiation (global FST = 0.0081) and weak isolation by distance following a stepping‐stone model. For the candidate adaptive loci, however, model‐based and model‐free approaches indicated five divergent population clusters. After controlling for spatial distance, the distribution of putatively adaptive variation was strongly correlated to selection linked to minimum sea surface temperature and oxygen concentration. Around 80 candidates were annotated to genes with functions related to high temperature and/or low oxygen tolerance, including genes that influence the resilience of abalone species found in other biogeographic regions. Our study includes a documented example about the uptake of genomic information in fisheries management and supports the hypothesis of adaptive divergence due to coastal environmental heterogeneity in a connected metapopulation of a broadcast spawner.
Functional biogeography and host specificity of bacterial communities associated with the Marine Green Alga Ulva spp.
Authors: Roth‐Schulze Alexandra J. , Pintado José , Zozaya‐Valdés Enrique , Cremades Javier , Ruiz Patricia , Kjelleberg Staffan , Thomas Torsten 
Published: February 2018

AbstractBacterial communities play an essential role for the function of marine macroalgae. Recent work has shown that bacterial communities associated with individual macroalgae possess on a local scale a functional core that is likely derived from diverse members of functional guilds. It is not known whether such functional cores also exist across large spatial scales or between closely related host species. To address this, we studied here the bacterial communities on three species of the green macroalgal genus Ulva from different geographic locations. While the taxonomic composition was too variable to describe a community core, we identified genes that were enriched across all Ulva samples as compared to the communities of the surrounding seawater. Of these core functions, 70% were consistently found and independent of the Ulva species and biogeography, while the remaining functions (~30%) are possibly involved in local or host‐specific adaptations. For each host individual, the core functions are provided by bacteria with distinct phylogenetic origin and these bacteria could constitute a global guild of Ulva‐associated bacteria. Together, our results demonstrate the presence of a stable core set of functional genes in the bacterial communities associated with closely related host species and across large biogeographies.
Recent work on reflective equilibrium and method in ethics
Authors: Tersman Folke 
Published: February 2018

AbstractThe idea of reflective equilibrium (IRE) remains the most popular approach to questions about method in ethics, despite the masses of criticism it has been faced with over the years. Is this due to the availability of compelling responses to the criticisms or rather to factors that are independent of its reasonableness? The aim of this paper is to provide support for the first answer. I particularly focus on the recent discussion. Some recent objections are related to general arguments against the possibility of moral knowledge, such as so‐called “evolutionary debunking arguments.” I argue that nothing that has come to light in that debate, or in the recent discussion about IRE more generally, decisively strengthens the case against it. If anything, the recent developments show that IRE deserves its present status.
Absorption Characteristics and Quantum Yields of Singlet Oxygen Generation of Thioguanosine Derivatives
Authors: Miyata Shoma , Yamada Takeshi , Isozaki Tasuku , Sugimura Hideyuki , Xu Yao–Zhong , Suzuki Tadashi 
Published: February 2018

Abstract
6‐Thioguanine (1a) is considered to be photochemotherapeutic due to its specific characteristics of photosensitivity to UVA light and singlet molecular oxygen generation. To extend its phototherapeutic ability, two related thioguanines, 8‐thioguanine (2a) and 6,8‐dithioguanine (3a), have been designed and explored. Since the solubility of these thioguanines in dehydrated organic solvents is too poor to study, their triacetyl‐protected ribonucleosides, that is, 2′,3′,5′‐tri‐O‐acetyl‐6‐thioguanosine (1c), 2′,3′,5′‐tri‐O‐acetyl‐8‐thioguanosine (2c) and 2′,3′,5′‐tri‐O‐acetyl‐6,8‐dithioguanosine (3c) were prepared and investigated. The absorption maxima of 1c, 2c and 3c in acetonitrile were found at longer wavelengths than that of unthiolated guanosine (4c). Especially, 3c has the longest wavelength for absorption maximum and the highest value in terms of molar absorption coefficient among all thionucleobases and thionucleosides reported. These absorption properties were also well reproduced by quantum chemical calculations. Quantum yields of singlet oxygen generation of 2c and 3c were determined by near‐infrared emission measurements to be as large as that of 1c. These results suggest that the newly synthesized thioguanosines, in particular 3c, can be further developed as a potential photosensitive agent for light‐induced therapies.
Bifunctional glycosyltransferases catalyze both extension and termination of pectic galactan oligosaccharides
Authors: Laursen Tomas , Stonebloom Solomon H. , Pidatala Venkataramana R. , Birdseye Devon S. , Clausen Mads H. , Mortimer Jenny C. , Scheller Henrik Vibe 
Published: February 2018

SummaryPectins are the most complex polysaccharides of the plant cell wall. Based on the number of methylations, acetylations and glycosidic linkages present in their structures, it is estimated that up to 67 transferase activities are involved in pectin biosynthesis. Pectic galactans constitute a major part of pectin in the form of side‐chains of rhamnogalacturonan‐I. In Arabidopsis, galactan synthase 1 (GALS1) catalyzes the addition of galactose units from UDP‐Gal to growing β‐1,4‐galactan chains. However, the mechanisms for obtaining varying degrees of polymerization remain poorly understood. In this study, we show that AtGALS1 is bifunctional, catalyzing both the transfer of galactose from UDP‐α‐d‐Gal and the transfer of an arabinopyranose from UDP‐β‐l‐Arap to galactan chains. The two substrates share a similar structure, but UDP‐α‐d‐Gal is the preferred substrate, with a 10‐fold higher affinity. Transfer of Arap to galactan prevents further addition of galactose residues, resulting in a lower degree of polymerization. We show that this dual activity occurs both in vitro and in vivo. The herein described bifunctionality of AtGALS1 may suggest that plants can produce the incredible structural diversity of polysaccharides without a dedicated glycosyltransferase for each glycosidic linkage.
Physical interactions among flavonoid enzymes in snapdragon and torenia reveal the diversity in the flavonoid metabolon organization of different plant species
Authors: Fujino Naoto , Tenma Natsuki , Waki Toshiyuki , Ito Keisuke , Komatsuzaki Yuki , Sugiyama Keigo , Yamazaki Tatsuya , Yoshida Saori , Hatayama Masayoshi , Yamashita Satoshi , Tanaka Yoshikazu , Motohashi Reiko , Denessiouk Konstantin , Takahashi Seiji , Nakayama Toru 
Published: February 2018

SummaryFlavonoid metabolons (weakly‐bound multi‐enzyme complexes of flavonoid enzymes) are believed to occur in diverse plant species. However, how flavonoid enzymes are organized to form a metabolon is unknown for most plant species. We analyzed the physical interaction partnerships of the flavonoid enzymes from two lamiales plants (snapdragon and torenia) that produce flavones and anthocyanins. In snapdragon, protein–protein interaction assays using yeast and plant systems revealed the following binary interactions: flavone synthase II (FNSII)/chalcone synthase (CHS); FNSII/chalcone isomerase (CHI); FNSII/dihydroflavonol 4‐reductase (DFR); CHS/CHI; CHI/DFR; and flavonoid 3′‐hydroxylase/CHI. These results along with the subcellular localizations and membrane associations of snapdragon flavonoid enzymes suggested that FNSII serves as a component of the flavonoid metabolon tethered to the endoplasmic reticulum (ER). The observed interaction partnerships and temporal gene expression patterns of flavonoid enzymes in red snapdragon petal cells suggested the flower stage‐dependent formation of the flavonoid metabolon, which accounted for the sequential flavone and anthocyanin accumulation patterns therein. We also identified interactions between FNSII and other flavonoid enzymes in torenia, in which the co‐suppression of FNSII expression was previously reported to diminish petal anthocyanin contents. The observed physical interactions among flavonoid enzymes of these plant species provided further evidence supporting the long‐suspected organization of flavonoid metabolons as enzyme complexes tethered to the ER via cytochrome P450, and illustrated how flavonoid metabolons mediate flower coloration. Moreover, the observed interaction partnerships were distinct from those previously identified in other plant species (Arabidopsis thaliana and soybean), suggesting that the organization of flavonoid metabolons may differ among plant species.
Determinants of Extreme β-Lactam Tolerance in the Burkholderia pseudomallei Complex
Authors: Held Kiara , Gasper Joe , Morgan Sarah , Siehnel Richard , Singh Pradeep , Manoil Colin 
Published: February 2018

ABSTRACT

Slow-growing bacteria are insensitive to killing by antibiotics, a trait known as antibiotic tolerance. In this study, we characterized the genetic basis of an unusually robust β-lactam (meropenem) tolerance seen in
Burkholderia
species. We identified tolerance genes under three different slow-growth conditions by extensive transposon mutant sequencing (Tn-seq), followed by single mutant validation. There were three principal findings. First, mutations in a small number of genes reduced tolerance under multiple conditions. Most of the functions appeared to be specific to peptidoglycan synthesis and the response to its disruption by meropenem action rather than being associated with more general physiological processes. The top tolerance genes are involved in immunity toward a type VI toxin targeting peptidoglycan (BTH_I0069), peptidoglycan recycling (
ldcA
), periplasmic regulation by proteolysis (
prc
), and an envelope stress response (
rpoE
and
degS
). Second, most of the tolerance functions did not contribute to growth in the presence of meropenem (intrinsic resistance), indicating that the two traits are largely distinct. Third, orthologues of many of the top
Burkholderia thailandensis
tolerance genes were also important in
Burkholderia pseudomallei
. Overall, these studies show that the determinants of meropenem tolerance differ considerably depending on cultivation conditions, but that there are a few shared functions with strong mutant phenotypes that are important in multiple
Burkholderia
species.
Functional Role of N-Linked Glycosylation in Pseudorabies Virus Glycoprotein gH
Authors: Vallbracht Melina , Rehwaldt Sascha , Klupp Barbara G. , Mettenleiter Thomas C. , Fuchs Walter 
Published: February 2018

ABSTRACT

Many viral envelope proteins are modified by asparagine (N)-linked glycosylation, which can influence their structure, physicochemical properties, intracellular transport, and function. Here, we systematically analyzed the functional relevance of N-linked glycans in the alphaherpesvirus pseudorabies virus (PrV) glycoprotein H (gH), which is an essential component of the conserved core herpesvirus fusion machinery. Upon gD-mediated receptor binding, the heterodimeric complex of gH and gL activates gB to mediate fusion of the viral envelope with the host cell membrane for viral entry. gH contains five potential N-linked glycosylation sites at positions 77, 162, 542, 604, and 627, which were inactivated by conservative mutations (asparagine to glutamine) singly or in combination. The mutated proteins were tested for correct expression and fusion activity. Additionally, the mutated gH genes were inserted into the PrV genome for analysis of function during virus infection. Our results demonstrate that all five sites are glycosylated. Inactivation of the PrV-specific N77 or the conserved N627 resulted in significantly reduced
in vitro
fusion activity, delayed penetration kinetics, and smaller virus plaques. Moreover, substitution of N627 greatly affected transport of gH in transfected cells, resulting in endoplasmic reticulum (ER) retention and reduced surface expression. In contrast, mutation of N604, which is conserved in the
Varicellovirus
genus, resulted in enhanced
in vitro
fusion activity and viral cell-to-cell spread. These results demonstrate a role of the N-glycans in proper localization and function of PrV gH. However, even simultaneous inactivation of all five N-glycosylation sites of gH did not severely inhibit formation of infectious virus particles.

IMPORTANCE
Herpesvirus infection requires fusion of the viral envelope with cellular membranes, which involves the conserved fusion machinery consisting of gB and the heterodimeric gH/gL complex. The bona fide fusion protein gB depends on the presence of the gH/gL complex for activation. Viral envelope glycoproteins, such as gH, usually contain N-glycans, which can have a strong impact on their folding, transport, and functions. Here, we systematically analyzed the functional relevance of all five predicted N-linked glycosylation sites in the alphaherpesvirus pseudorabies virus (PrV) gH. Despite the fact that mutation of specific sites affected gH transport,
in vitro
fusion activity, and cell-to-cell spread and resulted in delayed penetration kinetics, even simultaneous inactivation of all five N-glycosylation sites of gH did not severely inhibit formation of infectious virus particles. Thus, our results demonstrate a modulatory but nonessential role of N-glycans for gH function.
Effect of Long-Term Electroacupuncture Stimulation on Recovery of Sensorimotor Function after Peripheral Nerve Anastomosis
Authors: Zhang Mingxing , Zhang Ye , Bian Yuhong , Fu Hui , Xu Ying , Guo Yi 
Published: February 2018

Background Recently, application of electroacupuncture (EA) to stimulate nerve regeneration has become a mainstream treatment in clinical rehabilitation and related basic research, but the efficacy of long-term stimulation has not been confirmed. Objective To evaluate the influence of long term EA on peripheral nerve injury (PNI) from multiple angles. Method Twenty-four rats were divided into three groups: control, PNI and PNI+EA. In the latter two groups, PNI was modelled by transection followed by re-anastomosis of thesciatic nerve. In the PNI+EA group only, EA was delivered using a discontinuous wave with frequency 5 Hz, pulse width 2 ms, and intensity approximately 2 mA, until the affected limb was observed to twitch slightly. The treatment was given for 15 min each time, six times a week (continuously for 6 days followed by a 1-day break) for a total of 8 weeks. The effects of EA on anastomotic sciatic nerve regeneration were evaluated using the sciatic function index (SFI), mechanical withdrawal thresholds, thermo-nociceptive thresholds, conduction velocity of the sciatic nerve and bilateral gastrocnemius wet weight. Results From weeks 2 to 4 after modelling, the SFI recovery rate in the PNI+EA group was faster than that in the PNI group. In week 4, the SFI of the PNI+EA group was significantly higher than that of the PNI group (p<0.05). However, a significant effect of EA was no longer evident from weeks 5 to 8. There was no effect of acupuncture on anti-amyotrophy and conduction velocity of the sciatic nerve at 8 weeks after modelling. EA did not shorten the paw withdrawal threshold time, but appeared to alleviate thermo-nociceptive sensitivity. Conclusion Long term repeated stimulation of the same site with EA does not appear to be conducive to the functional recovery of an injured sciatic nerve in rats.
Multimorbidity and out-of-pocket expenditure on medicines: a systematic review
Authors: Sum Grace , Hone Thomas , Atun Rifat , Millett Christopher , Suhrcke Marc , Mahal Ajay , Koh Gerald Choon-Huat , Lee John Tayu 
Published: February 2018

BackgroundMultimorbidity, the presence of two or more non-communicable diseases (NCD), is a costly and complex challenge for health systems globally. Patients with NCDs incur high levels of out-of-pocket expenditure (OOPE), often on medicines, but the literature on the association between OOPE on medicines and multimorbidity has not been examined systematically.MethodsA systematic review was conducted via searching medical and economics databases including Ovid Medline, EMBASE, EconLit, Cochrane Library and the WHO Global Health Library from year 2000 to 2016. Study quality was assessed using Newcastle-Ottawa Scale. PROSPERO: CRD42016053538.Findings14 articles met inclusion criteria. Findings indicated that multimorbidity was associated with higher OOPE on medicines. When number of NCDs increased from 0 to 1, 2 and ≥3, annual OOPE on medicines increased by an average of 2.7 times, 5.2 times and 10.1 times, respectively. When number of NCDs increased from 0 to 1, 2, ≥2 and ≥3, individuals spent a median of 0.36% (IQR 0.15%–0.51%), 1.15% (IQR 0.62%–1.64%), 1.41% (IQR 0.86%–2.15%), 2.42% (IQR 2.05%–2.64%) and 2.63% (IQR 1.56%–4.13%) of mean annual household net adjusted disposable income per capita, respectively, on annual OOPE on medicines. More multimorbidities were associated with higher OOPE on medicines as a proportion of total healthcare expenditures by patients. Some evidence suggested that the elderly and low-income groups were most vulnerable to higher OOPE on medicines. With the same number of NCDs, certain combinations of NCDs yielded higher medicine OOPE. Non-adherence to medicines was a coping strategy for OOPE on medicines.ConclusionMultimorbidity of NCDs is increasingly costly to healthcare systems and OOPE on medicines can severely compromise financial protection and universal health coverage. It is crucial to recognise the need for better equity and financial protection, and policymakers should consider health system financial options, cost sharing policies and service patterns for those with NCD multimorbidities.