bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Transformation and Comparative Advantage: Implications for Small Open Economies
Authors: Whang Unjung 
Published: April 2016

AbstractData from the last half‐century show that revealed comparative advantage in agriculture (manufacturing) is negatively (positively) associated with the rate of decline in labour share in agriculture. Motivated by this finding, the author constructs and calibrates a simple open‐economy model, where there is learning‐by‐doing in manufacturing and industry‐supplied inputs to agricultural production. This paper focuses on the effects of comparative advantage and learning‐by‐doing on structural transformation and calibrate the model to the US and the UK data to estimate key parameters of the model. Quantitative experiments show that holding constant other factors a small difference in a country's comparative advantage can account for a large variation in structural transformation for open economies, which does not require nearly as much differential productivity growth as in closed‐economy models.
DNA methylation and targeted sequencing of methyltransferases family genes in canine acute myeloid leukaemia, modelling human myeloid leukaemia
Authors: Bronzini I. , Aresu L. , Paganin M. , Marchioretto L. , Comazzi S. , Cian F. , Riondato F. , Marconato L. , Martini V. , te Kronnie G. 
Published: April 2016

AbstractTumours shows aberrant DNA methylation patterns, being hypermethylated or hypomethylated compared with normal tissues. In human acute myeloid leukaemia (hAML) mutations in DNA methyltransferase (DNMT3A) are associated to a more aggressive tumour behaviour. As AML is lethal in dogs, we defined global DNA methylation content, and screened the C‐terminal domain of DNMT3 family of genes for sequence variants in 39 canine acute myeloid leukaemia (cAML) cases. A heterogeneous pattern of DNA methylation was found among cAML samples, with subsets of cases being hypermethylated or hypomethylated compared with healthy controls; four recurrent single nucleotide variations (SNVs) were found in DNMT3L gene. Although SNVs were not directly correlated to whole genome DNA methylation levels, all hypomethylated cAML cases were homozygous for the deleterious mutation at p.Arg222Trp. This study contributes to understand genetic modifications of cAML, leading up to studies that will elucidate the role of methylome alterations in the pathogenesis of AML in dogs.
Development and Validation of a Quantitative, One-Step, Multiplex, Real-Time Reverse Transcriptase PCR Assay for Detection of Dengue and Chikungunya Viruses
Authors: Simmons Monika , Myers Todd , Guevara Carolina , Jungkind Donald , Williams Maya , Houng Huo-Shu 
Published: April 2016

ABSTRACT

Dengue virus (DENV) and chikungunya virus (CHIKV) are important human pathogens with common transmission vectors and similar clinical presentations. Patient care may be impacted by the misdiagnosis of DENV and CHIKV in areas where both viruses cocirculate. In this study, we have developed and validated a one-step multiplex reverse transcriptase PCR (RT-PCR) to simultaneously detect, quantify, and differentiate between four DENV serotypes (pan-DENV) and chikungunya virus. The assay uses TaqMan technology, employing two forward primers, three reverse primers, and four fluorophore-labeled probes in a single-reaction format. Coextracted and coamplified RNA was used as an internal control (IC), and
in vitro
-transcribed DENV and CHIKV RNAs were used to generate standard curves for absolute quantification. The diagnostic 95% limits of detection (LOD) within the linear range were 50 and 60 RNA copies/reaction for DENV (serotypes 1 to 4) and CHIKV, respectively. Our assay was able to detect 53 different strains of DENV, representing four serotypes, and six strains of CHIKV. No cross-reactivity was observed with related flaviviruses and alphaviruses, To evaluate diagnostic sensitivity and specificity, 89 clinical samples positive or negative for DENV (serotypes 1 to 4) and CHIKV by the standard virus isolation method were tested in our assay. The multiplex RT-PCR assay showed 95% sensitivity and 100% specificity for DENV and 100% sensitivity and specificity for CHIKV. With an assay turnaround time of less than 2 h, including extraction of RNA, the multiplex quantitative RT-PCR assay provides rapid diagnosis for the differential detection of two clinically indistinguishable diseases, whose geographical occurrence is increasingly overlapping.
Epidemiology of Invasive Group B Streptococcal Disease in Alberta, Canada, from 2003 to 2013
Authors: Alhhazmi Areej , Hurteau Donna , Tyrrell Gregory J. 
Published: April 2016

ABSTRACT

Group B streptococci (GBS) cause severe invasive disease in both neonates and adults. Understanding the epidemiology of GBS provides information that can include determining disease prevalence rates in defined populations and geographic regions, documenting the success of GBS screening programs, and understanding antimicrobial susceptibility patterns. In Alberta, only neonatal invasive GBS (iGBS) disease is notifiable to health authorities. We performed a surveillance study of iGBS in Alberta, Canada, from 2003 to 2013. Over the 11-year period, the disease incidence rate increased from a low of 3.92 cases/100,000 population to a high of 5.99 cases/100,000 population. The capsular polysaccharide serotypes (CPSs) found were CPS III (20.3%), CPS V (19.1%), CPS Ia (18.9%), CPS Ib (12.7%), CPS II (11.1%), CPS IV (6.3%), and nontypeable GBS (9.4%). Rates of early-onset disease (0 to 7 days) increased from 0.15 cases/1,000 live births (in 2003) to 0.34 cases/1,000 live births (in 2013). Rates of late-onset disease (>7 to 90 days) also rose, from 0.15 cases/1,000 live births (in 2003) to 0.39 cases/1,000 live births (in 2013). Alberta also experienced an increase in CPS IV isolates, from 2 cases (in 2003) to 24 cases (in 2013), of which the majority were
hvgA
positive (86.6%). The predominant sequence type (ST) in 2013 was ST459. Erythromycin resistance rose from 23.6% to 43.9% (in 2013). Clindamycin resistance also increased, from 12.2% to 32.5%. In summary, Alberta, Canada, has experienced an increase in GBS disease; the increase includes both neonatal and adult disease. CPS IV cases also notably increased during the surveillance period, as did resistance to erythromycin and clindamycin.
Depletion of Alveolar Macrophages Does Not Prevent Hantavirus Disease Pathogenesis in Golden Syrian Hamsters
Authors: Hammerbeck Christopher D. , Brocato Rebecca L. , Bell Todd M. , Schellhase Christopher W. , Mraz Steven R. , Queen Laurie A. , Hooper Jay W. 
Published: April 2016

ABSTRACTAndes virus (ANDV) is associated with a lethal vascular leak syndrome in humans termed hantavirus pulmonary syndrome (HPS). The mechanism for the massive vascular leakage associated with HPS is poorly understood; however, dysregulation of components of the immune response is often suggested as a possible cause. Alveolar macrophages are found in the alveoli of the lung and represent the first line of defense to many airborne pathogens. To determine whether alveolar macrophages play a role in HPS pathogenesis, alveolar macrophages were depleted in an adult rodent model of HPS that closely resembles human HPS. Syrian hamsters were treated, intratracheally, with clodronate-encapsulated liposomes or control liposomes and were then challenged with ANDV. Treatment with clodronate-encapsulated liposomes resulted in significant reduction in alveolar macrophages, but depletion did not prevent pathogenesis or prolong disease. Depletion also did not significantly reduce the amount of virus in the lung of ANDV-infected hamsters but altered neutrophil recruitment, MIP-1α and MIP-2 chemokine expression, and vascular endothelial growth factor (VEGF) levels in hamster bronchoalveolar lavage (BAL) fluid early after intranasal challenge. These data demonstrate that alveolar macrophages may play a limited protective role early after exposure to aerosolized ANDV but do not directly contribute to hantavirus disease pathogenesis in the hamster model of HPS.IMPORTANCEHantaviruses continue to cause disease worldwide for which there are no FDA-licensed vaccines, effective postexposure prophylactics, or therapeutics. Much of this can be attributed to a poor understanding of the mechanism of hantavirus disease pathogenesis. Hantavirus disease has long been considered an immune-mediated disease; however, by directly manipulating the Syrian hamster model, we continue to eliminate individual immune cell types. As the most numerous immune cells present in the respiratory tract, alveolar macrophages are poised to defend against hantavirus infection, but those antiviral responses may also contribute to hantavirus disease. Here, we demonstrate that, like in our prior T and B cell studies, alveolar macrophages neither prevent hantavirus infection nor cause hantavirus disease. While these studies reflect pathogenesis in the hamster model, they should help us rule out specific cell types and prompt us to consider other potential mechanisms of disease in an effort to improve the outcome of human HPS.
Influenza Virus Hemagglutinin Glycoproteins with Different N-Glycan Patterns Activate Dendritic Cells
In Vitro
Authors: Liu Wen-Chun , Lin Yu-Li , Spearman Maureen , Cheng Pei-Yun , Butler Michael , Wu Suh-Chin 
Published: April 2016

ABSTRACT

Influenza virus hemagglutinin (HA) N-glycans play important regulatory roles in the control of virus virulence, antigenicity, receptor-binding specificity, and viral escape from the immune response. Considered essential for controlling innate and adaptive immune responses against influenza virus infections, dendritic cells (DCs) trigger proinflammatory and adaptive immune responses in hosts. In this study, we engineered Chinese hamster ovary (CHO) cell lines expressing recombinant HA from pandemic H1, H5, and H7 influenza viruses. rH1HA, rH5HA, and rH7HA were obtained as wild-type proteins or in the presence of kifunensine (KIF) or further with endo-β-
N
-acetylglucosaminidase-treated KIF (KIF+E) to generate single-
N
-acetylglucosamine (GlcNAc) N-glycans consisting of (i) terminally sialylated complex-type N-glycans, (ii) high-mannose-type N-glycans, and (iii) single-GlcNAc-type N-glycans. Our results show that high-mannose-type and single-GlcNAc-type N-glycans, but not complex-type N-glycans, are capable of inducing more active hIL12 p40, hIL12 p70, and hIL-10 production in human DCs. Significantly higher HLA-DR, CD40, CD83, and CD86 expression levels, as well reduced endocytotic capacity in human DCs, were noted in the high-mannose-type rH1HA and single-GlcNAc-type rH1HA groups than in the complex-type N-glycan rH1HA group. Our data indicate that native avian rHA proteins (H5N1 and H7N9) are more immunostimulatory than human rHA protein (pH1N1). The high-mannose-type or single-GlcNAc-type N-glycans of both avian and human HA types are more stimulatory than the complex-type N-glycans. HA-stimulated DC activation was accomplished partially through a mannose receptor(s). These results provide more understanding of the contribution of glycosylation of viral proteins to the immune responses and may have implications for vaccine development.

IMPORTANCE
Influenza viruses trigger seasonal epidemics or pandemics with mild-to-severe consequences for human and poultry populations. DCs are the most potent professional antigen-presenting cells, which play a crucial role in the link between innate and adaptive immunity. In this study, we obtained stable-expression CHO cells to produce rH1HA, rH5HA, and rH7HA proteins containing distinct N-glycan patterns. These rHA proteins, each with a distinct N-glycan pattern, were used to investigate interactions with mouse and human DCs. Our data indicate that native avian rHA proteins (H5N1 and H7N9) are more immunostimulatory than human rHA protein (pH1N1). High-mannose-type and single-GlcNAc-type N-glycans were more effective than complex-type N-glycans in triggering mouse and human DC activation and maturation. We believe these results provide some useful information for influenza vaccine development regarding how influenza virus HA proteins with different types of N-glycans activate DCs.
Epidemiology of neurological manifestations in Sjögren's syndrome: data from the French ASSESS Cohort
Authors: Carvajal Alegria Guillermo , Guellec Dewi , Mariette Xavier , Gottenberg Jacques-Eric , Dernis Emmanuelle , Dubost Jean-Jacques , Trouvin Anne-Priscille , Hachulla Eric , Larroche Claire , Le Guern Veronique , Cornec Divi , Devauchelle-Pensec Valérie , Saraux Alain 
Published: April 2016

ObjectivesNeurological manifestations seem common in primary Sjögren's syndrome (pSS) but their reported prevalences vary. We investigated the prevalence and epidemiology of neurological manifestations in a French nationwide multicentre prospective cohort of patients with pSS, the Assessment of Systemic Signs and Evolution in Sjögren's syndrome (ASSESS) cohort.MethodsThe ASSESS cohort, established in 2006, includes 395 patients fulfilling American–European Consensus Group criteria for pSS. Demographic and clinical data were compared between patient groups with and without neurological manifestations, and across patient groups with peripheral nervous system (PNS) manifestations, central nervous system (CNS) manifestations and no neurological manifestations.ResultsData at inclusion were available for 392 patients, whose mean age was 58±12 years. Mean follow-up was 33.9 months. Neurological manifestations were present in 74/392 (18.9%) patients, including 63 (16%) with PNS manifestations and 14 (3.6%) with CNS manifestations. Prevalences were 9.2% for pure sensory neuropathy, 5.3% for sensorimotor neuropathy, 1.3% for cerebral vasculitis and 1.0% for myelitis. Neurological manifestations were associated with greater pSS activity as assessed using the ESSDAI (9.4±6.8 vs 4.3±4.8; p<0.001) and proportion of patients taking immunomodulatory/immunosuppressive drugs (32.4% (24/74) versus 13.8% (44/318), p=0003). New neurological symptoms were more common in patients with than without prior neurological manifestations (RR=3.918 (95% CI 1.91 to 8.05); p<0.001).ConclusionsPrevalences of peripheral and central neurological manifestations in pSS are about 15% and 5%, respectively. Neurological manifestations are associated with greater pSS activity. New neurological manifestations are more common in patients with prior neurological involvement.
Block-Based High Capacity Multilevel Image Steganography
Authors: Kasana Geeta , Singh Kulbir , Bhatia Satvinder Singh 
Published: April 2016

This paper proposes a block-based high capacity steganography technique for digital images. The cover image is decomposed into blocks of equal size and the largest pixel of each block is found to embed the secret data bits and also the smallest pixel of each block is used for embedding to enhance the capacity. Embedding of secret data is performed using the concept that the pixel of a cover image has only two states — even and odd. Multilevel approach is also combined in the proposed technique to achieve high embedding capacity. In order to make the proposed technique more secure, a key is generated using embedding levels, block size, pixel embedding way, encryption parameters, and starting blocks of each embedding levels. Embedding capacity and visual quality of stego images generated by the proposed steganography technique are higher than the existing techniques. Steganalysis tests have been performed to show the un-detectability and imperceptibility of the proposed technique.
2-Phenethyl Isothiocyanate, Glutathione S-transferase M1 and T1 Polymorphisms, and Detoxification of Volatile Organic Carcinogens and Toxicants in Tobacco Smoke
Authors: Yuan Jian-Min , Murphy Sharon E. , Stepanov Irina , Wang Renwei , Carmella Steven G. , Nelson Heather H. , Hatsukami Dorothy , Hecht Stephen S. 
Published: April 2016

Abstract
Cigarette smoke contains relatively large quantities of volatile organic toxicants or carcinogens such as benzene, acrolein, and crotonaldehyde. Among their detoxification products are mercapturic acids formed from glutathione conjugation, catalyzed in part by glutathione S-transferases (GST). A randomized phase II clinical trial with a crossover design was conducted to evaluate the effect of 2-phenethyl isothiocyanate (PEITC), a natural product formed from gluconasturtiin in certain cruciferous vegetables, on the detoxification of benzene, acrolein, and crotonaldehyde in 82 cigarette smokers. Urinary mercapturic acids of benzene, acrolein, and crotonaldehyde at baseline and during treatment were quantified. Overall, oral PEITC supplementation increased the mercapturic acid formed from benzene by 24.6% (P = 0.002) and acrolein by 15.1% (P = 0.005), but had no effect on crotonaldehyde. A remarkably stronger effect was observed among subjects with the null genotype of both GSTM1 and GSTT1: in these individuals, PEITC increased the detoxification metabolite of benzene by 95.4% (P &lt; 0.001), of acrolein by 32.7% (P = 0.034), and of crotonaldehyde by 29.8% (P = 0.006). In contrast, PEITC had no effect on these mercapturic acids in smokers possessing both genes. PEITC had no effect on the urinary oxidative stress biomarker 8-iso-prostaglandin F2α or the inflammation biomarker prostaglandin E2 metabolite. This trial demonstrates an important role of PEITC in detoxification of environmental carcinogens and toxicants which also occur in cigarette smoke. The selective effect of PEITC on detoxification in subjects lacking both GSTM1 and GSTT1 genes supports the epidemiologic findings of stronger protection by dietary isothiocyanates against the development of lung cancer in such individuals. Cancer Prev Res; 9(7); 598–606. ©2016 AACR.
Morphine delays the onset of action of prasugrel in patients with prior history of ST-elevation myocardial infarction
Authors: Thomas Mark , Morton Allison , Hossain Rashed , Chen Beining , Luo Lei , Shahari Nur Nazihah , Hua Peng , Beniston Richard , Judge Heather , Storey Robert 
Published: April 2016

SummaryDelays in the onset of action of prasugrel during primary percutaneous coronary intervention (PPCI) have been reported and could be related to the effects of morphine on gastric emptying and subsequent intestinal absorption. The study objective was to determine whether morphine delays the onset of action of prasugrel in patients with a prior history of ST-elevation myocardial infarction (STEMI) treated with PPCI. This was a crossover study of 11 aspirin-treated patients with prior history of STEMI treated with PPCI, for which prasugrel and morphine had been previously administered. Patients were randomised to receive either morphine (5 mg) or saline intravenously followed by 60 mg prasugrel. Blood samples were collected before randomised treatment and over 24 hours after prasugrel administration. The inhibitory effects of prasugrel on platelets were determined using the VerifyNow P2Y12 assay and light transmission aggregometry. Plasma levels of prasugrel and prasugrel active metabolite were measured. Platelet reactivity determined by VerifyNow PRU, VerifyNow % Inhibition and LTA was significantly higher at 30–120 minutes (min) when morphine had been co-administered compared to when saline had been co-administered. Morphine, compared to saline, significantly delayed adequate platelet inhibition after prasugrel administration (158 vs 68 min; p = 0.006). Patients with delayed onset of platelet inhibition also had evidence of delayed absorption of prasugrel. In conclusion, prior administration of intravenous morphine significantly delays the onset of action of prasugrel. Intravenous drugs may be necessary to reduce the risk of acute stent thrombosis in morphine-treated STEMI patients undergoing PPCI.
Functional Versus Anatomic Assessment of Myocardial Bridging by Intravascular Ultrasound: Impact of Arterial Compression on Proximal Atherosclerotic Plaque
Authors: Yamada Ryotaro , Tremmel Jennifer A. , Tanaka Shigemitsu , Lin Shin , Kobayashi Yuhei , Hollak M. Brooke , Yock Paul G. , Fitzgerald Peter J. , Schnittger Ingela , Honda Yasuhiro 
Published: April 2016

Background

The presence of a myocardial bridge (
MB
) has been shown to promote atherosclerotic plaque formation proximal to the
MB
, presumably because of hemodynamic disturbances provoked by retrograde blood flow toward this segment in cardiac systole. We aimed to determine the anatomic and functional properties of an
MB
related to the extent of atherosclerosis assessed by intravascular ultrasound.

Methods and Results

We enrolled 100 patients with angina but no significant obstructive coronary artery disease who had an intravascular ultrasound–detected
MB
in the left anterior descending artery (median age 54 years, 36% male). The
MB
was identified with intravascular ultrasound by the presence of an echolucent band (halo). Anatomically, the
MB
length was 22±13 mm, and halo thickness was 0.7±0.6 mm. Functionally, systolic arterial compression was 23±12%. The maximum plaque burden up to 20 mm proximal to the
MB
entrance was significantly greater than the maximum plaque burden within the
MB
segment. Among the intravascular ultrasound–defined
MB
properties, arterial compression was the sole
MB
parameter that demonstrated a significant positive correlation with maximum plaque burden up to 20 mm proximal to the
MB
entrance (
r
=0.254,
P
=0.011 overall;
r
=0.545,
P
<0.001 low coronary risk). In multivariate analysis, adjusting for clinical characteristics and coronary risk factors, arterial compression was independently associated with maximum plaque burden up to 20 mm proximal to the
MB
entrance.

Conclusions

In patients with an MB in the left anterior descending artery, the percentage of arterial compression is related directly to the burden of atherosclerotic plaque located proximally to the
MB
, particularly in patients who otherwise have low coronary risk. This may prove helpful in identifying high‐risk
MB
patients.
Characteristics of Gravity Waves from Convection and Implications for Their Parameterization in Global Circulation Models
Authors: Stephan Claudia , Alexander M. Joan , Richter Jadwiga H. 
Published: April 2016

Abstract
Characteristic properties of gravity waves from convection over the continental United States are derived from idealized high-resolution numerical simulations. In a unique modeling approach, waves are forced by a realistic thermodynamic source based on observed precipitation data. The square of the precipitation rate and the gravity wave momentum fluxes both show lognormal occurrence distributions, with long tails of extreme events. Convectively generated waves can give forces in the lower stratosphere that at times rival orographic wave forcing. Throughout the stratosphere, zonal forces due to convective wave drag are much stronger than accounted for by current gravity wave drag parameterizations, so their contribution to the summer branch of the stratospheric Brewer–Dobson circulation is in fact much larger than models predict. A comparison of these forces to previous estimates of the total drag implies that convectively generated gravity waves are a primary source of summer-hemisphere stratospheric wave drag. Furthermore, intermittency and strength of the zonal forces due to convective gravity wave drag in the lower stratosphere resemble analysis increments, suggesting that a more realistic representation of these waves may help alleviate model biases on synoptic scales. The properties of radar precipitation and gravity waves seen in this study lead to a proposed change for future parameterization methods that would give more realistic drag forces in the stratosphere without compromising mesospheric gravity wave drag.