bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolation and Characterization of vΔI3 Confirm that Vaccinia Virus SSB Plays an Essential Role in Viral Replication
Authors: Greseth Matthew D. , Czarnecki Maciej W. , Bluma Matthew S. , Traktman Paula
Published: November 2017

Vaccinia virus is unusual among DNA viruses in replicating exclusively in the cytoplasm of infected cells. The single-stranded DNA (ssDNA) binding protein (SSB) I3 is among the replication machinery encoded by the 195-kb genome, although direct genetic analysis of I3 has been lacking. Herein, we describe a complementing cell line (CV1-I3) that fully supports the replication of a null virus (vΔI3) lacking the I3 open reading frame (ORF). In noncomplementing CV1-CAT cells, vΔI3 shows a severe defect in the production of infectious virus (≥200-fold reduction). Early protein synthesis and core disassembly occur normally. However, DNA replication is profoundly impaired (≤0.2% of wild-type [WT] levels), and late proteins do not accumulate. When several other noncomplementing cell lines are infected with vΔI3, the yield of infectious virus is also dramatically reduced (168- to 1,776-fold reduction). Surprisingly, the residual levels of DNA accumulation vary from 1 to 12% in the different cell lines (CV1-CAT < A549 < BSC40 < HeLa); however, any nascent DNA that can be detected is subgenomic in size. Although this subgenomic DNA supports late protein expression, it does not support the production of infectious virions. Electron microscopy (EM) analysis of vΔI3-infected BSC40 cells reveals that immature virions are abundant but no mature virions are observed. Aberrant virions characteristic of a block to genome encapsidation are seen instead. Finally, we demonstrate that a CV1 cell line encoding a previously described I3 variant with impaired ssDNA binding activity is unable to complement vΔI3. This report provides definitive evidence that the vaccinia virus I3 protein is the replicative SSB and is essential for productive viral replication.

IMPORTANCEPoxviruses are of historical and contemporary importance as infectious agents, vaccines, and oncolytic therapeutics. The cytoplasmic replication of poxviruses is unique among DNA viruses of mammalian cells and necessitates that the double-stranded DNA (dsDNA) genome encode the viral replication machinery. This study focuses on the I3 protein. As a ssDNA binding protein (SSB), I3 has been presumed to play essential roles in genome replication, recombination, and repair, although genetic analysis has been lacking. Herein, we report the characterization of an I3 deletion virus. In the absence of I3 expression, DNA replication is severely compromised and viral yield profoundly decreased. The production of infectious virus can be restored in a cell line expressing WT I3 but not in a cell line expressing an I3 mutant that is defective in ssDNA binding activity. These data show conclusively that I3 is an essential viral protein and functions as the viral replicative SSB.
MicroRNA-Based Attenuation of Influenza Virus across Susceptible Hosts
Authors: Waring Barbara M. , Sjaastad Louisa E. , Fiege Jessica K. , Fay Elizabeth J. , Reyes Ismarc , Moriarity Branden , Langlois Ryan A.
Published: November 2017

Influenza A virus drives significant morbidity and mortality in humans and livestock. Annual circulation of the virus in livestock and waterfowl contributes to severe economic disruption and increases the risk of zoonotic transmission of novel strains into the human population, where there is no preexisting immunity. Seasonal vaccinations in humans help prevent infection and can reduce symptoms when infection does occur. However, current vaccination regimens available for livestock are limited in part due to safety concerns regarding reassortment/recombination with circulating strains. Therefore, inactivated vaccines are used instead of the more immunostimulatory live attenuated vaccines. MicroRNAs (miRNAs) have been used previously to generate attenuated influenza A viruses for use as a vaccine. Here, we systematically targeted individual influenza gene mRNAs using the same miRNA to determine the segment(s) that yields maximal attenuation potential. This analysis demonstrated that targeting of NP mRNA most efficiently ablates replication. We further increased the plasticity of miRNA-mediated attenuation of influenza A virus by exploiting a miRNA, miR-21, that is ubiquitously expressed across influenza-susceptible hosts. In order to construct this targeted virus, we used CRISPR/Cas9 to eliminate the universally expressed miR-21 from MDCK cells. miR-21-targeted viruses were attenuated in human, mouse, canine, and avian cells and drove protective immunity in mice. This strategy has the potential to enhance the safety of live attenuated vaccines in humans and zoonotic reservoirs.

IMPORTANCEInfluenza A virus circulates annually in both avian and human populations, causing significant morbidity, mortality, and economic burden. High incidence of zoonotic infections greatly increases the potential for transmission to humans, where no preexisting immunity or vaccine exists. There is a critical need for new vaccine strategies to combat emerging influenza outbreaks. MicroRNAs were used previously to attenuate influenza A viruses. We propose the development of a novel platform to produce live attenuated vaccines that are highly customizable, efficacious across a broad species range, and exhibit enhanced safety over traditional vaccination methods. This strategy exploits a microRNA that is expressed abundantly in influenza virus-susceptible hosts. By eliminating this ubiquitous microRNA from a cell line, targeted viruses that are attenuated across susceptible strains can be generated. This approach greatly increases the plasticity of the microRNA targeting approach and enhances vaccine safety.
The Ubiquitin-Proteasome System Is Necessary for Efficient Replication of Human Astrovirus
Authors: Casorla-Pérez Luis A. , López Tomás , López Susana , Arias Carlos F.
Published: November 2017

Astroviruses, members of the family
Astroviridae
, represent an important cause of human gastroenteritis in the world. The cellular factors required for astrovirus replication have been poorly studied. In this work, we evaluated the relevance of the ubiquitin-proteasome system (UPS) in the replication of Yuc8, a human astrovirus serotype 8 strain. We found that proteasome inhibitors decrease the production of infectious viral progeny at a step in the replication cycle subsequent to virus entry. The inhibition of proteasome activity decreases viral RNA levels and viral protein synthesis; similarly, the inhibition of ubiquitination by chemical inhibitors or RNA interference (RNAi) reduces the production of viral progeny as well as viral protein synthesis. The effect on viral progeny production induced by proteasome inhibitors is not explained by a reduction in the pool of monoubiquitin or the induction of early apoptosis or autophagy. Our observations are consistent with the need of the proteolytic activity of the UPS for the efficient replication of the virus and suggest that UPS is necessary for the production of genomic and subgenomic RNA but not for antigenomic RNA.

IMPORTANCE
Astroviruses are a major cause of gastroenteritis in young humans and animals, and recently, it was associated with fatal encephalitis in humans. The role of the ubiquitin-proteasome system in the replication of these viruses has not been studied previously. In this work, we present evidence that supports that the proteolytic activity of the proteasome is necessary for efficient viral progeny production and that this proteolytic system is required for the accumulation of both genomic and subgenomic viral RNAs.
Multiple endocrine neoplasia type 1 presenting with refractory seizures
Authors: Kumawat Banshi Lal , Sharma Chandramohan , Shah Mohit Janakkumar , Panchal Maulik
Published: November 2017

We report a case of 29-year-old woman referred to us for management of refractory epilepsy. Under observation, she was detected to have recurrent hypoglycaemia during the episodes of seizures. On investigation, she was found to have hyperinsulinemic hypoglycaemia. Her triple-phase CT scan of abdomen showed neuroendocrine tumour of pancreatic head, with bilateral renal calculi. Screening of other endocrine glands revealed pituitary microadenoma and parathyroid adenoma on imaging, which was also supported by biochemical and hormonal profile. On the basis of tumours involving parathyroid, pancreatic islets and pituitary gland, she was diagnosed as a case of multiple endocrine neoplasia type 1. Pancreatic tumour removal was done and bromocriptine was started. She was followed up for 6 months postoperatively and never had seizures even without antiepileptic drugs. This case report highlights an exceptional treatable cause of uncontrolled seizures.
Gerstmann-Sträussler-Scheinker disease with atypical presentation
Authors: Keuss Sarah E , Ironside James W , O’Riordan Jonathan
Published: November 2017

We describe a 37-year-old woman who presented with progressive deafness, visual loss and ataxia. She latterly developed neuropsychiatric problems, including cognitive impairment, paranoid delusions and episodes of altered consciousness. She was found to be heterozygous for the Q212P mutation in the prion protein gene. She died over a decade after initial presentation and a diagnosis of prion disease was confirmed at postmortem.
What is health systems responsiveness? Review of existing knowledge and proposed conceptual framework
Authors: Mirzoev Tolib , Kane Sumit
Published: November 2017

Responsiveness is a key objective of national health systems. Responsive health systems anticipate and adapt to existing and future health needs, thus contributing to better health outcomes. Of all the health systems objectives, responsiveness is the least studied, which perhaps reflects lack of comprehensive frameworks that go beyond the normative characteristics of responsive services. This paper contributes to a growing, yet limited, knowledge on this topic. Herewith, we review the current frameworks for understanding health systems responsiveness and drawing on these, as well as key frameworks from the wider public services literature, propose a comprehensive conceptual framework for health systems responsiveness. This paper should be of interest to different stakeholders who are engaged in analysing and improving health systems responsiveness. Our review shows that existing knowledge on health systems responsiveness can be extended along the three areas. First, responsiveness entails an actual experience of people’s interaction with their health system, which confirms or disconfirms their initial expectations of the system. Second, the experience of interaction is shaped by both the people and the health systems sides of this interaction. Third, different influences shape people’s interaction with their health system, ultimately affecting their resultant experiences. Therefore, recognition of both people and health systems sides of interaction and their key determinants would enhance the conceptualisations of responsiveness. Our proposed framework builds on, and advances, the core frameworks in the health systems literature. It positions the experience of interaction between people and health system as the centrepiece and recognises the determinants of responsiveness experience both from the health systems (eg, actors, processes) and the people (eg, initial expectations) sides. While we hope to trigger further thinking on the conceptualisation of health system responsiveness, the proposed framework can guide assessments of, and interventions to strengthen, health systems responsiveness.
Antimicrobial resistance and universal health coverage
Authors: Bloom Gerald , Merrett Gemma Buckland , Wilkinson Annie , Lin Vivian , Paulin Sarah
Published: November 2017

The WHO launched a Global Action Plan on antimicrobial resistance (AMR) in 2015. World leaders in the G7, G20 and the UN General Assembly have declared AMR to be a global crisis. World leaders have also adopted universal health coverage (UHC) as a key target under the sustainable development goals. This paper argues that neither initiative is likely to succeed in isolation from the other and that the policy goals should be to both provide access to appropriate antimicrobial treatment and reduce the risk of the emergence and spread of resistance by taking a systems approach. It focuses on outpatient treatment of human infections and identifies a number of interventions that would be needed to achieve these policy goals. It then shows how a strategy for achieving key attributes of a health system for UHC can take into account the need to address AMR as part of a UHC strategy in any country. It concludes with a list of recommended priority actions for integrating initiatives on AMR and UHC.
Are objective measures of physical capability related to accelerated epigenetic age? Findings from a British birth cohort
Authors: Simpkin Andrew J , Cooper Rachel , Howe Laura D , Relton Caroline L , Davey Smith George , Teschendorff Andrew , Widschwendter Martin , Wong Andrew , Kuh Diana , Hardy Rebecca
Published: November 2017

Objectives

Our aim was to investigate the association of epigenetic age and physical capability in later life. Having a higher epigenetic than chronological age (known as age acceleration (AA)) has been found to be associated with an increased rate of mortality. Similarly, physical capability has been proposed as a marker of ageing due to its consistent associations with mortality.

Setting

The MRC National Survey of Health and Development (NSHD) cohort study.

Participants

We used data from 790 women from the NSHD who had DNA methylation data available.

Design

Epigenetic age was calculated using buccal cell (n=790) and matched blood tissue (n=152) from 790 female NSHD participants. We investigated the association of AA at age 53 with changes in physical capability in women from ages 53 to 60–64. Regression models of change in each measure of physical capability on AA were conducted. Secondary analysis focused on the relationship between AA and smoking, alcohol, body mass index (BMI) and socioeconomic position.

Outcome measures

Three objective measures of physical capability were used: grip strength, standing balance time and chair rise speed.

Results

Epigenetic age was lower than chronological age (mean 53.4) for both blood (50.3) and buccal cells (42.8). AA from blood was associated with a greater decrease in grip strength from ages 53 to 60–64 (0.42 kg decrease per year of AA, 95% CI 0.03, 0.82 kg; p=0.03, n=152), but no associations were observed with standing balance time or chair rise speed. Current smoking and lower BMI were associated with lower epigenetic age from buccal cells.

Conclusions

We found evidence that AA in blood is associated with a greater decrease in grip strength in British females aged between 53 and 60–64, but no association with standing balance time or chair rise speed was found.
Influence of socioeconomic factors on pregnancy outcome in women with structural heart disease
Authors: van Hagen Iris M , Baart Sara , Fong Soe Khioe Rebekah , Sliwa-Hahnle Karen , Taha Nasser , Lelonek Malgorzata , Tavazzi Luigi , Maggioni Aldo Pietro , Johnson Mark R , Maniadakis Nikolaos , Fordham Richard , Hall Roger , Roos-Hesselink Jolien W
Published: November 2017

Objective

Cardiac disease is the leading cause of indirect maternal mortality. The aim of this study was to analyse to what extent socioeconomic factors influence the outcome of pregnancy in women with heart disease.

Methods

The Registry of Pregnancy and Cardiac disease is a global prospective registry. For this analysis, countries that enrolled ≥10 patients were included. A combined cardiac endpoint included maternal cardiac death, arrhythmia requiring treatment, heart failure, thromboembolic event, aortic dissection, endocarditis, acute coronary syndrome, hospitalisation for cardiac reason or intervention. Associations between patient characteristics, country characteristics (income inequality expressed as Gini coefficient, health expenditure, schooling, gross domestic product, birth rate and hospital beds) and cardiac endpoints were checked in a three-level model (patient–centre–country).

Results

A total of 30 countries enrolled 2924 patients from 89 centres. At least one endpoint occurred in 645 women (22.1%). Maternal age, New York Heart Association classification and modified WHO risk classification were associated with the combined endpoint and explained 37% of variance in outcome. Gini coefficient and country-specific birth rate explained an additional 4%. There were large differences between the individual countries, but the need for multilevel modelling to account for these differences disappeared after adjustment for patient characteristics, Gini and country-specific birth rate.

Conclusion

While there are definite interregional differences in pregnancy outcome in women with cardiac disease, these differences seem to be mainly driven by individual patient characteristics. Adjustment for country characteristics refined the results to a limited extent, but maternal condition seems to be the main determinant of outcome.
Use of oral anticoagulants in combination with antiplatelet(s) in atrial fibrillation
Authors: Sindet-Pedersen Caroline , Staerk Laila , Lamberts Morten , Gerds Thomas Alexander , Berger Jeffrey S , Nissen Bonde Anders , Langtved Pallisgaard Jannik , Hansen Morten Lock , Torp-Pedersen Christian , Gislason Gunnar H , Bjerring Olesen Jonas
Published: November 2017

Objectives

To investigate temporal trends in the use of non-vitamin K oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) in combination with aspirin and/or clopidogrel in patients with atrial fibrillation (AF) following acute myocardial infarction (MI) and/or percutaneous coronary intervention (PCI).

Methods

Using Danish nationwide registries, all patients with AF who survived 30 days after discharge from MI and/or PCI between 22 August 2011 and 30 September 2016 were identified.

Results

A total of 2946 patients were included in the study population, of whom 1967 (66.8%) patients were treated with VKA in combination with antiplatelet(s) (VKA+aspirin n=477, VKA+clopidogrel n=439, VKA+aspirin+clopidogrel n=1051) and 979 (33.2%) patients were treated with NOAC in combination with antiplatelet(s) (NOAC+aspirin n=252, NOAC+clopidogrel n=218, NOAC+aspirin+clopidogrel n=509). The overall study population had a median age of 76 years [IQR: 69–82] and consisted of 1995 (67.7%) men. Patients with MI as inclusion event accounted for 1613 patients (54.8%). Patients with high CHA2DS2-VASc score(congestive heart failure, hypertension, age ≥75 years (2 points), diabetes mellitus, history of stroke/transient ischemic attack/systemic thromboembolism (2 points), vascular disease, age 65-75 years, and female sex) accounted for 132 2814 (95.5%) of patients, and patients with high HAS-BLED score (hypertension, abnormal renal/liver function, history of stroke, history of bleeding, age >65 years, non-steroidal anti-inflammatory drug usages, or alcohol abuse, leaving out labile international normalized ratio (not available), and use of antiplatelets (exposure variable)) accounted for 934 (31.7%) of patients. There was an increase from 10% in 2011 to 52% in 2016 in the use of NOACs in combination with antiplatelet(s).

Conclusion

From 2011 to 2016, the use of NOAC in combination with antiplatelet(s) increased in patients with AF following MI/PCI and exceeded the use of VKA in combination with antiplatelet(s) by 2016.
A propensity score-adjusted analysis of clinical outcomes after pulmonary valve replacement in tetralogy of Fallot
Authors: Bokma Jouke P , Geva Tal , Sleeper Lynn A , Babu Narayan Sonya V , Wald Rachel , Hickey Kelsey , Jansen Katrijn , Wassall Rebecca , Lu Minmin , Gatzoulis Michael A , Mulder Barbara JM , Valente Anne Marie
Published: November 2017

Objective

To determine the association of pulmonary valve replacement (PVR) with death and sustained ventricular tachycardia (VT) in patients with repaired tetralogy of Fallot (rTOF).

Methods

Subjects with rTOF and cardiac magnetic resonance from an international registry were included. A PVR propensity score was created to adjust for baseline differences. PVR consensus criteria were predefined as pulmonary regurgitation >25% and ≥2 of the following criteria: right ventricular (RV) end-diastolic volume >160 mL/m2, RV end-systolic volume >80 mL/m2, RV ejection fraction (EF) <47%, left ventricular EF <55% and QRS duration >160 ms. The primary outcome included (aborted) death and sustained VT. The secondary outcome included heart failure, non-sustained VT and sustained supraventricular tachycardia.

Results

In 977 rTOF subjects (age 26±15 years, 45% PVR, follow-up 5.3±3.1 years), the primary and secondary outcomes occurred in 41 and 88 subjects, respectively. The HR for subjects with versus without PVR (time-varying covariate) was 0.65 (95% CI 0.31 to 1.36; P=0.25) for the primary outcome and 1.43 (95% CI 0.83 to 2.46; P=0.19) for the secondary outcome after adjusting for propensity and other factors. In subjects (n=426) not meeting consensus criteria, the HR for subjects with (n=132) versus without (n=294) PVR was 2.53 (95% CI 0.79 to 8.06; P=0.12) for the primary outcome and 2.31 (95% CI 1.07 to 4.97; P=0.03) for the secondary outcome.

Conclusion

In this large multicentre rTOF cohort, PVR was not associated with a reduced rate of death and sustained VT at an average follow-up of 5.3 years. Additionally, there were more events after PVR compared with no PVR in subjects not meeting consensus criteria.
The ageing heart: the systemic and coronary circulation
Authors: Nanayakkara Shane , Marwick Thomas H , Kaye David M
Published: November 2017

Most cardiovascular disease (CVD) occurs in patients over the age of 60. However, most evidence-based current cardiovascular guidelines lack evidence in an older population, due to the under-representation of older patients in randomised trials. Blood pressure rises with age due to increasing arterial stiffness, and stricter control results in improved outcomes. Myocardial ischaemia is also more common with increasing age, due to a combination of coronary artery disease and myocardial changes. However, despite higher rates of adverse outcomes, older patients are offered guideline-based therapy less frequently. Frailty is an independent predictor of mortality in adults over the age of 60, yet remains poorly assessed; slow gait speed is a key marker for the development of frailty and for adverse outcomes following intervention. Few trials have assessed frailty independent of age; however, there is evidence that non-frail older patients derive significant benefit from therapy, highlighting the urgent need to include frailty as a measure in clinical trials of treatment in CVD.

In this review, the authors appraise the literature in regard to the cardiovascular changes with ageing, specifically in relation to the systemic and coronary circulation and with a particular emphasis on frailty and its implication in the evaluation and treatment of CVD.
Flow diversion for anterior choroidal artery (AChA) aneurysms: a multi-institutional experience
Authors: Srinivasan Visish M , Ghali Michael George Zaki , Cherian Jacob , Mokin Maxim , Puri Ajit S , Grandhi Ramesh , Chen Stephen R , Johnson Jeremiah N , Kan Peter
Published: November 2017

Background

Anterior choroidal artery (AChA) aneurysms represent a small subset of cerebral aneurysms. The Pipeline Embolization Device (PED) has been successfully applied to various aneurysms of the supraclinoid internal carotid artery (ICA). The treatment of these aneurysms requires special attention due to the eloquent territory supplied by the AChA. We report the largest and first dedicated series of flow diversion treatment of AChA aneurysms.

Methods

Four institutional neurointerventional databases were reviewed for cases of intracranial aneurysms treated with PED. Patient and aneurysm data as well as angiographic imaging were reviewed for all cases of AChA aneurysms treated with PED. AChA aneurysms were defined as aneurysms distal to the AChA and proximal to the ICA terminus, with or without the incorporation of the AChA.

Results

Eighteen AChA aneurysms were treated during the study period. All aneurysms were successfully treated with a mean follow-up of 19.1 months. The large majority of aneurysms (15/18, 83.3%) were completely obliterated. No patients suffered from intra- or post-procedural complications. A1 stenosis was a common occurrence, seen in 10 of 16 (62.5%) covered anterior cerebral arteries (ACAs), although all were asymptomatic. All AChAs remained patent at last follow-up.

Conclusions

The PED can be used successfully in AChA aneurysms with a good safety and efficacy profile. All AChAs remained patent. Collateral flow networks, especially for the ACA, affect long-term branch vessel patency. Treatment with PED for AChA aneurysms appears to be a reasonable option to consider and should be evaluated in a larger cohort.
Effects ofSpirulina platensison lipid peroxidation, antioxidant defenses, and tissue damage in kidney of alloxan-induced diabetic rats
Authors: Gargouri Manel , Hamed Houda , Akrouti Amel , Dauvergne Xavier , Magné Christian , El Feki Abdelfattah
Published: November 2017

Chronic hyperglycemia in diabetes causes free radicals overproduction, which contributes to the development of diabetic nephropathy. In modern medicine, no satisfactory therapy is available to cure diabetes mellitus. In that context, we investigated the potential therapeutic action of spirulina-enriched diet on renal impairment and oxidative stress in diabetic rats. Diabetes was induced by a single subcutaneous injection of alloxan (120 mg·kg−1) in rats. Following alloxan treatment, male Wistar rats were fed daily with 5% spirulina-enriched diet or treated with insulin (0.5 IU·rat−1) for 3 weeks. Diabetes was associated with hyperglycemia, increase in renal oxidative parameters (lipid peroxidation, thiobarbituric-acid reactive substances, protein carbonyl and advanced oxidation protein products levels, changes in antioxidant enzyme activities), and nephropathology markers. The renal injury induced by alloxan was confirmed by histological study of the diabetic rat kidney. Treatment with spirulina or insulin significantly ameliorated renal dysfunction by reducing oxidative stress, while rats recovered normal kidney histology. Overall, this study indicates that spirulina is efficient in inhibiting hyperglycemia and oxidative stress induced by diabetes, and suggests that the administration of this alga may be helpful in the prevention of diabetic complications. This amelioration was even more pronounced than that caused by insulin injection.
H-NS represses transcription of the flagellin gene lafA of lateral flagella in Vibrio parahaemolyticus
Authors: Wang Yan , Zhang Yiquan , Yin Zhe , Wang Jie , Zhu Yongzhe , Peng Haoran , Zhou Dongsheng , Qi Zhongtian , Yang Wenhui
Published: November 2017

Swarming motility is ultimately mediated by the proton-powered lateral flagellar (laf) system in Vibrio parahaemolyticus. Expression of laf genes is tightly regulated by a number of environmental conditions and regulatory factors. The nucleoid-associated DNA-binding protein H-NS is a small and abundant protein that is widely distributed in bacteria, and H-NS-like protein-dependent expression of laf genes has been identified in Vibrio cholerae and V. parahaemolyticus. The data presented here show that H-NS acts as a repressor of the swarming motility in V. parahaemolyticus. A single σ28-dependent promoter was detected for lafA encoding the flagellin of the lateral flagella, and its activity was directly repressed by H-NS. Thus, H-NS represses swarming motility by directly acting on lafA. Briefly, this work revealed a novel function for H-NS as a repressor of the expression of lafA and swarming motility in V. parahaemolyticus.
AN EXPLICIT IMPLIED VOLATILITY FORMULA
Authors: STEFANICA DAN , RADOIČIĆ RADOŠ
Published: November 2017

We show that an explicit approximate implied volatility formula can be obtained from a Black–Scholes formula approximation that is 2% accurate. The relative error of the approximate implied volatility is uniformly bounded for options with any moneyness and with arbitrary large or small option maturities and volatilities, including for long dated options and options on highly volatile underlying assets. For options within a large trading range, such as options with maturity less than five years and implied volatility less than 150%, the error of the approximate implied volatility relative to the Black–Scholes implied volatility is less than 10% points.
GENDER DISPARITIES IN SCIENCE? DROPOUT, PRODUCTIVITY, COLLABORATIONS AND SUCCESS OF MALE AND FEMALE COMPUTER SCIENTISTS
Authors: JADIDI MOHSEN , KARIMI FARIBA , LIETZ HAIKO , WAGNER CLAUDIA
Published: November 2017

Scientific collaborations shape ideas as well as innovations and are both the substrate for, and the outcome of, academic careers. Recent studies show that gender inequality is still present in many scientific practices ranging from hiring to peer-review processes and grant applications. In this work, we investigate gender-specific differences in collaboration patterns of more than one million computer scientists over the course of 47 years. We explore how these patterns change over years and career ages and how they impact scientific success. Our results highlight that successful male and female scientists reveal the same collaboration patterns: compared to scientists in the same career age, they tend to collaborate with more colleagues than other scientists, seek innovations as brokers and establish longer-lasting and more repetitive collaborations. However, women are on average less likely to adopt the collaboration patterns that are related with success, more likely to embed into ego networks devoid of structural holes, and they exhibit stronger gender homophily as well as a consistently higher dropout rate than men in all career ages.
ROLE OF NEUTRAL EVOLUTION IN WORD TURNOVER DURING CENTURIES OF ENGLISH WORD POPULARITY
Authors: RUCK DAMIAN , ALEXANDER BENTLEY R. , ACERBI ALBERTO , GARNETT PHILIP , HRUSCHKA DANIEL J.
Published: November 2017

Here, we test Neutral models against the evolution of English word frequency and vocabulary at the corpus scale, as recorded in annual word frequencies from three centuries of English language books. Against these data, we test both static and dynamic predictions of two neutral models, including the relation between corpus size and vocabulary size, frequency distributions, and turnover within those frequency distributions. Although a commonly used Neutral model fails to replicate all these emergent properties at once, we find that modified two-stage Neutral model does replicate the static and dynamic properties of the corpus data. This two-stage model is meant to represent a relatively small corpus of English books, analogous to a ‘canon’, sampled by an exponentially increasing corpus of books among the wider population of authors. More broadly, this model — a smaller neutral model within a larger neutral model — could represent more broadly those situations where mass attention is focused on a small subset of the cultural variants.
Vector potential quantization and the photon intrinsic electromagnetic properties: Towards nondestructive photon detection
Authors: Meis Constantin , Dahoo Pierre Richard
Published: November 2017

We employ here the enhancement of the vector potential amplitude quantization at a single photon state. The analysis of the general solution of the vector potential, obtained by resolving Maxwell’s equations, implies that the amplitude is proportional to the angular frequency. The photon vector potential function αkλ(r,t) can be written in the plane wave representation satisfying the classical wave propagation equation, Schrödinger’s equation for the energy with the relativistic massless field Hamiltonian and a linear time-dependent equation for the vector potential amplitude operator. Thus, the vector potential αkλ(r,t) with the quantized amplitude may play the role of a real wave function for the photon in a nonlocal representation that can be suitably normalized. We then deduce that the amplitudes of the electric and magnetic fields, respectively, of a single free photon are proportional to the square of the angular frequency. This might open perspectives for the development of nondestructive photon detection methods based on the influence of the electric and/or magnetic fields of photons on the energy levels of atoms and molecules.
Dielectric properties of composite based on ferroelectric copolymer of poly(vinylidene fluoride-trifluoroethylene) and ferroelectric ceramics of barium lead zirconate titanate
Authors: Solnyshkin A. V. , Kislova I. L. , Morsakov I. M. , Belov A. N. , Shevyakov V. I. , Kiselev D. A. , Shvartsman V. V.
Published: November 2017

A study of dielectric properties of composite films on the base of poly(vinylidene fluoride-trifluoroethylene) copolymer P(VDF-TrFE) and ferroelectric ceramics of barium lead zirconate titanate (BPZT) solid solution is presented in this work. The composite films containing up to 50 vol.% of BPZT grains with size [Formula: see text]1[Formula: see text][Formula: see text]m were prepared by the solvent cast method. Frequency dependences of real and imaginary components of the complex permittivity were determined. The concentration dependence of the dielectric constant was discussed.
Specific heat of a PIN-PMN-PT single-crystal up to 500K
Authors: Grabovsky S. , Shnaidshtein I. , Przeslawski J. , Li Zhenrong , Xu Zhuo , Strukov B.
Published: November 2017

The temperature dependence of the specific heat of the single crystal Pb(In[Formula: see text]Nb[Formula: see text])O3-Pb(Mg[Formula: see text]Nb[Formula: see text])O3-PbTiO3 (PIN-PMN-PT) was obtained at 80–500[Formula: see text]K by means of ac-calorimetry, and comparison with the calorimetric data for PMN was made, allowing one to determine absolute values of the specific heat of PIN-PMN-PT. For the high-temperature region ([Formula: see text][Formula: see text]K), the background heat capacity was calculated, the anomalies of the heat capacity for both compounds were determined, and the hump of the temperature dependence of specific heat PIN-PMN-PT was detected for the first time.
Analyzing memory management methods on integrated CPU-GPU systems
Authors: Dashti Mohammad , Fedorova Alexandra
Published: November 2017

Heterogeneous systems that integrate a multicore CPU and a GPU on the same die are ubiquitous. On these systems, both the CPU and GPU share the same physical memory as opposed to using separate memory dies. Although integration eliminates the need to copy data between the CPU and the GPU, arranging transparent memory sharing between the two devices can carry large overheads. Memory on CPU/GPU systems is typically managed by a software framework such as OpenCL or CUDA, which includes a runtime library, and communicates with a GPU driver. These frameworks offer a range of memory management methods that vary in ease of use, consistency guarantees and performance. In this study, we analyze some of the common memory management methods of the most widely used software frameworks for heterogeneous systems: CUDA, OpenCL 1.2, OpenCL 2.0, and HSA, on NVIDIA and AMD hardware. We focus on performance/functionality trade-offs, with the goal of exposing their performance impact and simplifying the choice of memory management methods for programmers.
Flexible and efficient memory object metadata
Authors: Liu Zhengyang , Criswell John
Published: November 2017

Compiler-based tools can protect software from attack and find bugs within programs. To support programs written in type-unsafe languages such as C, such tools need to add code into a program that must, at run-time, take a pointer into a memory object and locate metadata for that memory object. Current methods of locating metadata are either flexible (supporting metadata of varying sizes) at the expense of speed and scalability or are fast (e.g., by using shadow tables) at the cost of flexibility (metadata is small and must always be the same size).

This paper presents a new method of attaching metadata to memory objects, named Padding Area MetaData (PAMD), that is both flexible and efficient. Metadata can be any size, and different memory objects can have different sized metadata. While flexible, the algorithm for finding the metadata given a pointer into the memory object takes constant time. Our method extends Baggy Bounds with Accurate Checking (BBAC) which attaches constant-sized metadata to memory objects for performing precise dynamic bounds checks. Our design supports variable-sized metadata, and our implementation supports larger programs.

We evaluated the performance and scalability of PAMD using dynamic bounds checking as an exemplar of our method. Our results show that our method adds at most 33% overhead to an identical dynamic bounds checking tool that trades precision for performance by using a simple shadow table. Our results also show that our method, while having the same flexibility as splay trees, performs significantly faster and scales better as a program allocates more memory.
Continuous checkpointing of HTM transactions in NVM
Authors: Giles Ellis , Doshi Kshitij , Varman Peter
Published: November 2017

This paper addresses the challenges of coupling byte addressable non-volatile memory (NVM) and hardware transaction memory (HTM) in high-performance transaction processing. We first show that HTM transactions can be ordered using existing processor instructions without any hardware changes. In contrast, existing solutions posit changes to HTM mechanisms in the form of special instructions or modified functionality. We exploit the ordering mechanism to design a novel persistence method that decouples HTM concurrency from back-end NVM operations. Failure atomicity is achieved using redo logging coupled with aliasing to guard against mistimed cache evictions. Our algorithm uses efficient lock-free mechanisms with bounded static memory requirements. We evaluated our approach using both micro-benchmarks, and, benchmarks in the STAMP suite, and showed that it compares well with standard (volatile) HTM transactions. We also showed that it yields significant gains in throughput and latency in comparison with persistent transactional locking.
Avoiding consistency exceptions under strong memory models
Authors: Zhang Minjia , Biswas Swarnendu , Bond Michael D.
Published: November 2017

Shared-memory languages and systems generally provide weak or undefined semantics for executions with data races. Prior work has proposed memory consistency models that ensure well-defined, easy-to-understand semantics based on
region serializability
(RS), but the resulting system may throw a
consistency exception
in the presence of a data race. Consistency exceptions can occur unexpectedly even in well-tested programs, hurting availability and thus limiting the practicality of RS-based memory models.

To our knowledge, this paper is the first to consider the problem of availability for memory consistency models that throw consistency exceptions. We first extend existing approaches that enforce
RSx
, a memory model based on serializability of synchronization-free regions (SFRs), to avoid region conflicts and thus consistency exceptions. These new approaches demonstrate both the potential for and limitations of avoiding consistency exceptions under RSx. To improve availability further, we introduce (1) a new memory model called
RIx
based on
isolation
of SFRs and (2) a new approach called
Avalon
that provides RIx. We demonstrate two variants of Avalon that offer different performance-availability tradeoffs for RIx.

An evaluation on real Java programs shows that this work's novel approaches are able to reduce consistency exceptions, thereby improving the applicability of strong memory consistency models. Furthermore, the approaches provide compelling points in the performance-availability tradeoff space for memory consistency enforcement. RIx and Avalon thus represent a promising direction for tackling the challenge of availability under strong consistency models that throw consistency exceptions.
NG2C: pretenuring garbage collection with dynamic generations for HotSpot big data applications
Authors: Bruno Rodrigo , Oliveira Luís Picciochi , Ferreira Paulo
Published: November 2017

Big Data applications suffer from unpredictable and unacceptably high pause times due to Garbage Collection (GC). This is the case in latency-sensitive applications such as on-line credit-card fraud detection, graph-based computing for analysis on social networks, etc. Such pauses compromise latency requirements of the whole application stack and result from applications' aggressive buffering/caching of data, exposing an ill-suited GC design, which assumes that most objects will die young and does not consider that applications hold large amounts of middle-lived data in memory.

To avoid such pauses, we propose NG2C, a new GC algorithm that combines pretenuring with user-defined dynamic generations. By being able to allocate objects into different generations, NG2C is able to group objects with similar lifetime profiles in the same generation. By allocating objects with similar lifetime profiles close to each other, i.e. in the same generation, we avoid object promotion (copying between generations) and heap fragmentation (which leads to heap compactions) both responsible for most of the duration of HotSpot GC pause times.

NG2C is implemented for the OpenJDK 8 HotSpot Java Virtual Machine, as an extension of the Garbage First GC. We evaluate NG2C using Cassandra, Lucene, and GraphChi with three different GCs: Garbage First (G1), Concurrent Mark Sweep (CMS), and NG2C. Results show that NG2C decreases the worst observable GC pause time by up to 94.8% for Cassandra, 85.0% for Lucene and 96.45% for GraphChi, when compared to current collectors (G1 and CMS). In addition, NG2c has no negative impact on application throughput or memory usage.
A refinement hierarchy for free list memory allocators
Authors: Fang Bin , Sighireanu Mihaela
Published: November 2017

Existing implementations of dynamic memory allocators (DMA) employ a large spectrum of policies and techniques. The formal specifications of these techniques are quite complicated in isolation and very complex when combined. Therefore, the formal reasoning on a specific DMA implementation is difficult for automatic tools and mostly single-use. This paper proposes a solution to this problem by providing formal models for a full class of DMA, the free list class. To obtain manageable formal reasoning and reusable formal models, we organize these models in a hierarchy ranked by refinement relations. We prove the soundness of models and refinement relations using an off-the-shelf theorem prover. We demonstrate that our hierarchy is a basis for an algorithm theory for the class of free list DMA: it abstracts various existing implementations of DMA and leads to new DMA implementations. We illustrate its application to model-based code generation, testing, run-time verification, and static analysis.
A tale of two provers: verifying monoidal string matching in liquid Haskell and Coq
Authors: Vazou Niki , Lampropoulos Leonidas , Polakow Jeff
Published: November 2017

We demonstrate for the first time that Liquid Haskell, a refinement type checker for Haskell programs, can be used for arbitrary theorem proving by verifying a parallel, monoidal string matching algorithm implemented in Haskell. We use refinement types to specify correctness properties, Haskell terms to express proofs of these properties, and Liquid Haskell to check the proofs. We evaluate Liquid Haskell as a theorem prover by replicating our 1428 LoC proof in a dependently-typed language (Coq - 1136 LoC). Finally, we compare both proofs, uncovering the relative advantages and disadvantages of the two provers.
Elaboration on functional dependencies: functional dependencies are dead, long live functional dependencies!
Authors: Karachalias Georgios , Schrijvers Tom
Published: November 2017

Functional dependencies
are a popular extension to Haskell's type-class system because they provide fine-grained control over type inference, resolve ambiguities and even enable type-level computations.

Unfortunately, several aspects of Haskell's functional dependencies are ill-understood. In particular, the GHC compiler does not properly enforce the functional dependency property, and rejects well-typed programs because it does not know how to elaborate them into its core language, System F
C
.

This paper presents a novel formalization of functional dependencies that addresses these issues: We explicitly capture the functional dependency property in the type system, in the form of explicit type equalities. We also provide a type inference algorithm and an accompanying elaboration strategy which allows all well-typed programs to be elaborated into System F
C
.
Quantified class constraints
Authors: Bottu Gert-Jan , Karachalias Georgios , Schrijvers Tom , Oliveira Bruno C. d. S. , Wadler Philip
Published: November 2017

Quantified class constraints have been proposed many years ago to raise the expressive power of type classes from Horn clauses to the universal fragment of Hereditiary Harrop logic. Yet, while it has been much asked for over the years, the feature was never implemented or studied in depth. Instead, several workarounds have been proposed, all of which are ultimately stopgap measures.

This paper revisits the idea of quantified class constraints and elaborates it into a practical language design. We show the merit of quantified class constraints in terms of more
expressive modeling
and in terms of
terminating type class resolution
. In addition, we provide a declarative specification of the type system as well as a type inference algorithm that elaborates into System F. Moreover, we discuss termination conditions of our system and also provide a prototype implementation.
Improving STM performance with transactional structs
Authors: Yates Ryan , Scott Michael L.
Published: November 2017

Software transactional memory (STM) has made it significantly easier to write correct concurrent programs in Haskell. Its performance, however, is limited by several inefficiencies. While safe concurrent computations are easy to express in Haskell's STM, concurrent data structures suffer unfortunate bloat in the implementation due to an extra level of indirection for mutable references as well as the inability to express unboxed mutable transactional values. We address these deficiencies by introducing TStruct to the GHC run-time system, allowing strict unboxed transactional values as well as mutable references without an extra indirection. Using TStruct we implement several data structures, discuss their design, and provide benchmark results on a large multicore machine. Our benchmarks show that concurrent data structures built with TStruct out-scale and out-perform their TVar-based equivalents.