bluuebunny/crossref_metadata_2025 huggingface dataset:
The pre-eminent good argument
Authors: BOZZO ALEXANDER
Published: February 2019

According to J. L. Schellenberg, a perfectly loving God wouldn't permit the occurrence of non-resistant non-believers – that is, non-believers who are both capable of believing in and relating to God, but who fail to believe through no fault of their own. Since non-resistant non-believers exist, says Schellenberg, it follows that God doesn't. A popular response to this argument is some version or other of the greater good defence. God, it's argued, is justified in hiding himself when done for the sake of some greater good. But proponents of this defence have overlooked or neglected an important sub-argument in Schellenberg's case – what I call the ‘pre-eminent good argument’. In this article, I identify the nature of the argument and offer a solution to it.
Complaints about technology as a resource for identity-work
Authors: Robles Jessica S. , Parks Elizabeth S.
Published: February 2019

This article examines how people complain about technology. Using discourse analysis, we inspect sixteen hours of video-recorded focus-group interviews and focused one-on-one discussions where technology was topicalized. We investigate these conversations paying attention to (i) features of language and its situated delivery, including emphasis, word choice, metaphor, and categorizations; and (ii) how these accomplish social actions. We show how interactants use narratives of complaint-like activities about hypothetical categories of people and confessions of their own complainable participation to accomplish a ‘bemoaning’ speech act that manages competing affiliations, demands, and disagreements to construct reasonable moral identities in the situated interaction. By engaging in specific micro-level discursive practices in interaction, participants produce and reproduce what new technologies ‘mean’ to them and for contemporary society. This shows how important it is to examine opinions as situated actions rather than as simple facts about what people believe. (Complaints, accounts, stance, technology, discourse analysis, identity)*
Healthcare: between a human and a conventional right
Authors: Pavel Carmen E.
Published: February 2019

One of the most prevalent rationales for public healthcare policies is a human right to healthcare. Governments are the typical duty-bearers, but they differ vastly in their capacity to help those vulnerable to serious health problems and those with severe disabilities. A right to healthcare is out of the reach of many developing economies that struggle to provide the most basic services to their citizens. If human rights to provision of such goods exist, then governments would be violating rights without doing anything wrong. I argue that such variable ability to provide healthcare depends not only on financial resources, but on institutional capacity, and that the latter represents a more fundamental challenge to the existence of a human right to healthcare than previously recognized. This challenge does not imply that government has no obligations to protect and improve the health of their citizens, but that it is best to think of such obligations as generated by conventional rights, namely rights arising from local legal and social conventions, which require governments to pursue health-related moral goals such as reducing suffering, closing opportunity gaps for the disadvantaged, and preventing the spread of contagious diseases. We need not think of such moral goals in terms of human rights.
High prevalence of selected viruses and parasites and their predictors in Malawian children
Authors: Fan Y.-M. , Oikarinen S. , Lehto K.-M. , Nurminen N. , Juuti R. , Mangani C. , Maleta K. , Hyöty H. , Ashorn P.
Published: February 2019

Enteric pathogens have been related to child undernutrition. Whereas there are lots of data on enteric bacterial microbiota and infections, much less is known about the incidence of prevalence of intestinal colonisation with viruses or important parasitic species. This study assessed the presence of selected viruses and parasites in stools of 469, 354, 468 Malawian children at 6, 12 and 18 months. We also assessed environmental predictors of the presence of viruses and parasites among 6-month infants. Microbial presence was documented using real-time polymerase chain reaction (PCR). Enteroviruses were identified in 68%, 80% and 81% of the stool samples at 6, 12 and 18 months children, rhinovirus in 28%, 18% and 31%, norovirus in 24%, 22% and 16%, parechovirus in 23%, 17% and 17%, rotavirus in 3%, 1% and 0.6%,Giardia lambliain 9.6%, 23.5% and 26%, andCryptosporidium(spp.) in 6%, 8% and 2% of the 6, 12 and 18 months stool samples. Dry season (May–October) was associated with a low infection rate of enterovirus, norovirus andCryptosporidium(spp.). Higher father's education level, less number of person in the household and higher sanitation were associated with a low infection rate of enterovirus, norovirus and rotavirus, respectively. The results suggest that the prevalence of asymptomatic viral and parasitic infections is high among Malawian children and that the family's living conditions and seasonality influence the rate of infections.
Nipah virus infection: A review
Authors: Aditi  , Shariff M.
Published: February 2019

Nipah virus (NiV) is an emerging bat-borne pathogen. It was first identified 20 years ago in Malaysia and has since caused outbreaks in other parts of South and Southeast Asia. It causes severe neurological and respiratory disease which is highly lethal. It is highly infectious and spreads in the community through infected animals or other infected people. Different strains of the virus show differing clinical and epidemiological features. Rapid diagnosis and implementation of infection control measures are essential to contain outbreaks. A number of serological and molecular diagnostic techniques have been developed for diagnosis and surveillance. Difficulties in diagnosis and management arise when a new area is affected. The high mortality associated with infection and the possibility of spread to new areas has underscored the need for effective management and control. However, no effective treatment or prophylaxis is readily available, though several approaches show promise. Given the common chains of transmission from bats to humans, a One Health approach is necessary for the prevention and control of NiV infection.
Characterizing the Transition From Balanced to Unbalanced Motions in the Southern California Current
Authors: Chereskin Teresa K. , Rocha Cesar B. , Gille Sarah T. , Menemenlis Dimitris , Passaro Marcello
Published: February 2019

As observations and models improve their resolution of oceanic motions at ever finer horizontal scales, interest has grown in characterizing the transition from the geostrophically balanced flows that dominate at large‐scale to submesoscale turbulence and waves that dominate at small scales. In this study we examine the mesoscale‐to‐submesoscale (100 to 10 km) transition in an eastern boundary current, the southern California Current System (CCS), using repeated acoustic Doppler current profiler transects, sea surface height from high‐resolution nadir altimetry and output from a (1/48)° global model simulation. In the CCS, the submesoscale is as energetic as in western boundary current regions, but the mesoscale is much weaker, and as a result the transition lacks the change in kinetic energy (KE) spectral slope observed for western boundary currents. Helmholtz and vortex‐wave decompositions of the KE spectra are used to identify balanced and unbalanced contributions. At horizontal scales greater than 70 km, we find that observed KE is dominated by balanced geostrophic motions. At scales from 40 to 10 km, unbalanced contributions such as inertia‐gravity waves contribute as much as balanced motions. The model KE transition occurs at longer scales, around 125 km. The altimeter spectra are consistent with acoustic Doppler current profiler/model spectra at scales longer than 70/125 km, respectively. Observed seasonality is weak. Taken together, our results suggest that geostrophic velocities can be diagnosed from sea surface height on scales larger than about 70 km in the southern CCS.
Representation of Model Error in Convective‐Scale Data Assimilation: Additive Noise Based on Model Truncation Error
Authors: Zeng Yuefei , Janjić Tijana , Sommer Matthias , de Lozar Alberto , Blahak Ulrich , Seifert Axel
Published: February 2019

To account for model error on multiple scales in convective‐scale data assimilation, we incorporate the small‐scale additive noise based on random samples of model truncation error and combine it with the large‐scale additive noise based on random samples from global climatological atmospheric background error covariance. A series of experiments have been executed in the framework of the operational Kilometre‐scale ENsemble Data Assimilation system of the Deutscher Wetterdienst for a 2‐week period with different types of synoptic forcing of convection (i.e., strong or weak forcing). It is shown that the combination of large‐ and small‐scale additive noise is better than the application of large‐scale noise only. The specific increase in the background ensemble spread during data assimilation enhances the quality of short‐term 6‐hr precipitation forecasts. The improvement is especially significant during the weak forcing period, since the small‐scale additive noise increases the small‐scale variability which may favor occurrence of convection. It is also shown that additional perturbation of vertical velocity can further advance the performance of combination.
Tumor-derived exosomal HMGB1 promotes esophageal squamous cell carcinoma progression through inducing PD1+ TAM expansion
Authors: Li Bin , Song Tie-Niu , Wang Fu-Rong , Yin Ci , Li Zheng , Lin Jun-Ping , Meng Yu-Qi , Feng Hai-Ming , Jing Tao
Published: February 2019

Macrophages constitute one of the most common components of immune cells, which penetrate tumors and they have a key role in tumor prognosis. Here, we identified an unrecognized macrophage subpopulation, which favors tumorigenesis. These macrophages express programmed cell death protein 1 (PD1) in a constitutive manner and accumulates in esophageal squamous cell carcinoma (ESCC) in advanced stage of the disease and is negatively associated with the survival of ESCC patients. The PD1+ tumor-associated macrophages (PD1+ TAMs) displayed surface pattern and function akin to M2: a substantial enhancement in CD206 and IL-10 expression; a specific reduction in HLA-DR, CD64, and IL-12 expression; and a significant increase in the ability to inhibit CD8+ T-cell proliferation. Triggering of PD1 signal is effective in increasing PD1+ TAM function. Moreover, exosomal HMGB1 obtained from tumors are efficient in triggering differentiation of monocytes into PD1+ TAMs, which display phenotypic and functional properties of M2. Overall, our work is the first finding to confirm that exosomal HMGB1 obtained from ESCC can successfully trigger clonal expansion of PD1+ TAM. Further, as the macrophages exhibit an M2-like surface profile and function, thereby creating conditions for development of ESCC. Thus, effective methods of treatment include combining immunotherapy with targeting PD1+ TAMs and tumor-derived exosomal HMGB1 to resuscitate immune function in individuals suffering from ESCC.
Saikosaponin D suppresses enterovirus A71 infection by inhibiting autophagy
Authors: Li Chang , Huang Lihong , Sun Wei , Chen Ying , He Ming-Liang , Yue Jianbo , Ballard Heather
Published: February 2019

The dysregulation of autophagy, an evolutionarily conserved lysosomal degradation process, has been implicated in a wide variety of human diseases, and thus, small chemicals that modulate autophagy have therapeutic potential. Here, we assessed the ability of active components isolated from Bupleurum falcatum, a popular Chinese herb, to modulate autophagy. We found that saikosaponin D (SsD) and A (SsA) but not C (SsC) potently and reversibly inhibited the fusion of autophagosomes and lysosomes, resulting in the accumulation of autophagosomes, an increased lysosomal pH, and TFEB nuclear translocation. RAB5A knockdown or the expression of a dominant-negative RAB5 mutant significantly reduced the ability of SsD or SsA to block autophagy. Enterovirus A71 (EV-A71), the cause of hand-foot-mouth disease, has been shown to induce autophagy. We found that SsD potently inhibited EV-A71 RNA replication and subsequent viral protein synthesis, thereby preventing EV-A71-induced cell death. ATG5 knockdown inhibited EV-A71 viral protein synthesis, whereas autophagy induction by rapamycin promoted synthesis. Taken together, our data indicate that SsD and SsA are potent late-stage autophagy inhibitors that can be used to prevent EV-A71 infection.
Gambogic acid triggers vacuolization-associated cell death in cancer cells via disruption of thiol proteostasis
Authors: Seo Min Ji , Lee Dong Min , Kim In Young , Lee Dongjoo , Choi Min-Koo , Lee Joo-Youn , Park Seok Soon , Jeong Seong-Yun , Choi Eun Kyung , Choi Kyeong Sook
Published: February 2019

Gambogic acid (GA), a xanthonoid extracted from the resin of the tree,Garcinia hanburyi, was recently shown to exert anticancer activity in multiple studies, but the underlying action mechanism remains unclear. Here, we show that GA induces cancer cell death accompanied by vacuolation in vitro and in vivo. This GA-induced vacuolation in various cancer cells was derived from dilation of the endoplasmic reticulum (ER) and mitochondria, and was blocked by cycloheximide. These findings suggest that GA kills cancer cells by inducing paraptosis, a vacuolization-associated cell death. We found that megamitochondria formation, which arose from the fusion of swollen mitochondria, preceded the fusion of ER-derived vacuoles. GA-induced proteasomal inhibition was found to contribute to the ER dilation and ER stress seen in treated cancer cells, and megamitochondria formation was followed by mitochondrial membrane depolarization. Interestingly, GA-induced paraptosis was effectively blocked by various thiol-containing antioxidants, and this effect was independent of ROS generation. We observed that GA can react with cysteinyl thiol to form Michael adducts, suggesting that the ability of GA to covalently modify the nucleophilic cysteinyl groups of proteins may cause protein misfolding and subsequent accumulation of misfolded proteins within the ER and mitochondria. Collectively, our findings show that disruption of thiol proteostasis and subsequent paraptosis may critically contribute to the anti-cancer effects of GA.
MiR-15b and miR-322 inhibit SETD3 expression to repress muscle cell differentiation
Authors: Zhao Meng-Jie , Xie Jun , Shu Wen-Jie , Wang Hong-Yan , Bi Jianping , Jiang Wei , Du Hai-Ning
Published: February 2019

SETD3 is a member of SET-domain containing methyltransferase family, which plays critical roles in various biological events. It has been shown that SETD3 could regulate the transcription of myogenic regulatory genes in C2C12 differentiation and promote myoblast determination. However, how SETD3 is regulated during myoblast differentiation is still unknown. Here, we report that two important microRNAs (miRNAs) could repress SETD3 and negatively contribute to myoblast differentiation. Using microRNA (miRNA) prediction engines, we identify and characterize miR-15b and miR-322 as the primary miRNAs that repress the expression of SETD3 through directly targeting the 3’-untranslated region of SETD3 gene. Functionally, overexpression of miR-15b or miR-322 leads to the repression of endogenous SETD3 expression and the inhibition of myoblast differentiation, whereas inhibition of miR-15b or miR-322 derepresses endogenous SETD3 expression and facilitates myoblast differentiation. In addition, knockdown SETD3 in miR-15b or miR-322 repressed myoblasts is able to rescue the facilitated differentiation phenotype. More interestingly, we revealed that transcription factor E2F1 or FAM3B positively or negatively regulates miR-15b or miR-322 expression, respectively, during muscle cell differentiation, which in turn affects SETD3 expression. Therefore, our results establish two parallel cascade regulatory pathways, in which transcription factors regulate microRNAs fates, thereby controlling SETD3 expression and eventually determining skeletal muscle differentiation.
Circular RNA circBACH2 plays a role in papillary thyroid carcinoma by sponging miR-139-5p and regulating LMO4 expression
Authors: Cai Xiaoyan , Zhao Zheng , Dong Jiangnan , Lv Qiang , Yun Bei , Liu Jiangqi , Shen Yan , Kang Jie , Li Jun
Published: February 2019

Circular RNAs (circRNAs) are a class of non-coding RNAs that are broadly expressed in various biological cells and function in regulating gene expression. They are structurally stable and tissue-specific. However, the function of human circRNAs and the role of circRNAs in papillary thyroid carcinoma (PTC) remain to be determined. Herein, the function of circRNA circBACH2 was investigated in human PTC cells. First, we detected the expression of circBACH2 in PTC tissues and PTC cell lines by RT-PCR. FISH was used to confirm the subcellular localization of circBACH2. A luciferase reporter assay and AGO2-RIP was used to confirm the relationship between circBACH2 and miR-139-5p. PTC cells were stably transfected with siRNA against circBACH2 and cell proliferation, migration and invasion were detected to evaluate the effect of circBACH2 in PTC, while tumorigenesis was assayed in nude mice. We found that circBACH2 was highly expressed in PTC tissues and PTC cell lines. Mechanistically, we confirmed that circBACH2 could directly bind to miR-139-5p and relieve suppression of the target LMO4. Functionally, we found that inhibiting circBACH2 expression decreased cell proliferation, migration, and invasion. Finally, down-regulating circBACH2 suppressed the growth of PTC xenografts in nude mice. Our findings indicate that circBACH2 acts as a novel oncogenic RNA that sponges miR-139-5p and can be used as a tumor biomarker of PTC. What’s more, these results revealed that the circBACH2/miR-139-5p/LMO4 axis could be targeted as a potential treatment strategy for PTC.
A healthy individual with a homozygous PTCH2 frameshift variant: Are variants of PTCH2 associated with nevoid basal cell carcinoma syndrome?
Authors: Altaraihi M. , Wadt K. , Ek J. , Gerdes A. M. , Ostergaard E.
Published: February 2019

Variants in PTCH2 have been described to be associated with Nevoid Basal Cell Carcinoma Syndrome (NBCCS). We report a family with a healthy female who is homozygous for a frameshift variant, c.269delG, p.(Gly90Alafs*4), in PTCH2 and her heterozygous daughter. The variant predicts a frameshift and a premature stop codon. A summary of reported heterozygous individuals with germline PTCH2 variants along with the existence of a healthy homozygous individual question whether variants in PTCH2 are associated with NBCCS.
Sensing intracellular calcium ions using a manganese-based MRI contrast agent
Authors: Barandov Ali , Bartelle Benjamin B. , Williamson Catherine G. , Loucks Emily S. , Lippard Stephen J. , Jasanoff Alan
Published: February 2019

Calcium ions are essential to signal transduction in virtually all cells, where they coordinate processes ranging from embryogenesis to neural function. Although optical probes for intracellular calcium imaging have been available for decades, the development of probes for noninvasive detection of intracellular calcium signaling in deep tissue and intact organisms remains a challenge. To address this problem, we synthesized a manganese-based paramagnetic contrast agent, ManICS1-AM, designed to permeate cells, undergo esterase cleavage, and allow intracellular calcium levels to be monitored by magnetic resonance imaging (MRI). Cells loaded with ManICS1-AM show changes in MRI contrast when stimulated with pharmacological agents or optogenetic tools; responses directly parallel the signals obtained using fluorescent calcium indicators. Introduction of ManICS1-AM into rodent brains furthermore permits MRI-based measurement of neural activation in optically inaccessible brain regions. These results thus validate ManICS1-AM as a calcium sensor compatible with the extensive penetration depth and field of view afforded by MRI.
STAT1 signaling shields T cells from NK cell-mediated cytotoxicity
Authors: Kang Yu Hui , Biswas Amlan , Field Michael , Snapper Scott B.
Published: February 2019

The JAK-STAT pathway critically regulates T-cell differentiation, and STAT1 is postulated to regulate several immune-mediated diseases by inducing proinflammatory subsets. Here we show that STAT1 enables CD4+T-cell-mediated intestinal inflammation by protecting them from natural killer (NK) cell-mediated elimination.Stat1−/−T cells fail to expand and establish colitis in lymphopenic mice. This defect is not fully recapitulated by the combinatorial loss of type I and II IFN signaling. Mechanistically,Stat1−/−T cells have reduced expression ofNlrc5and multiple MHC class I molecules that serve to protect cells from NK cell-mediated killing. Consequently, the depletion of NK cells significantly rescues the survival and spontaneous proliferation ofStat1−/−T cells, and restores their ability to induce colitis in adoptive transfer mouse models.Stat1−/−mice however have normal CD4+T cell numbers as innate STAT1 signaling is required for their elimination. Overall, our findings reveal a critical perspective on JAK-STAT1 signaling that might apply to multiple inflammatory diseases.
Author Correction: Solution-processed perovskite light emitting diodes with efficiency exceeding 15% through additive-controlled nanostructure tailoring
Authors: Ban Muyang , Zou Yatao , Rivett Jasmine P. H. , Yang Yingguo , Thomas Tudor H. , Tan Yeshu , Song Tao , Gao Xingyu , Credgington Dan , Deschler Felix , Sirringhaus Henning , Sun Baoquan
Published: February 2019

The original version of this Article contained an error in the spelling of the author Dan Credgington, which was incorrectly given as Dan Credington. This has now been corrected in both the PDF and HTML versions of the Article.
A Novel Role of Prolidase in Cocaine-Mediated Breach in the Barrier of Brain Microvascular Endothelial Cells
Authors: Ysrayl Binah baht , Balasubramaniam Muthukumar , Albert Ife , Villalta Fernando , Pandhare Jui , Dash Chandravanu
Published: February 2019

Cocaine use is associated with breach in the blood brain barrier (BBB) and increased HIV-1 neuro-invasion. We show that the cellular enzyme “Prolidase” plays a key role in cocaine-induced disruption of the BBB. We established a barrier model to mimic the BBB by culturing human brain microvascular endothelial cells (HBMECs) in transwell inserts. In this model, cocaine treatment enhanced permeability of FITC-dextran suggesting a breach in the barrier. Interestingly, cocaine treatment increased the activity of matrix metallo-proteinases that initiate degradation of the BBB-associated collagen. Cocaine exposure also induced prolidase expression and activity in HBMECs. Prolidase catalyzes the final and rate-limiting step of collagen degradation during BBB remodeling. Knock-down of prolidase abrogated cocaine-mediated increased permeability suggesting a direct role of prolidase in BBB breach. To decipher the mechanism by which cocaine regulates prolidase, we probed the inducible nitric oxide synthase (iNOS) mediated phosphorylation of prolidase since mRNA levels of the protein were not altered upon cocaine treatment. We observed increased iNOS expression concurrent with increased prolidase phosphorylation in cocaine treated cells. Subsequently, inhibition of iNOS decreased prolidase phosphorylation and reduced cocaine-mediated permeability. Finally, cocaine treatment increased transmigration of monocytic cells through the HBMEC barrier. Knock-down of prolidase reduced cocaine-mediated monocyte transmigration, establishing a key role of prolidase in cocaine-induced breach in endothelial cell barrier.
Evolutionary dynamics of the chromatophore genome in three photosynthetic Paulinella species
Authors: Lhee Duckhyun , Ha Ji-San , Kim Sunju , Park Myung Gil , Bhattacharya Debashish , Yoon Hwan Su
Published: February 2019

The thecate amoeba Paulinella is a valuable model for understanding plastid organellogenesis because this lineage has independently gained plastids (termed chromatophores) of alpha-cyanobacterial provenance. Plastid primary endosymbiosis in Paulinella occurred relatively recently (90–140 million years ago, Mya), whereas the origin of the canonical Archaeplastida plastid occurred >1,500 Mya. Therefore, these two events provide independent perspectives on plastid formation on vastly different timescales. Here we generated the complete chromatophore genome sequence from P. longichromatophora (979,356 bp, GC-content = 38.8%, 915 predicted genes) and P. micropora NZ27 (977,190 bp, GC-content = 39.9%, 911 predicted genes) and compared these data to that from existing chromatophore genomes. Our analysis suggests that when a basal split occurred among photosynthetic Paulinella species ca. 60 Mya, only 35% of the ancestral orthologous gene families from the cyanobacterial endosymbiont remained in chromatophore DNA. Following major gene losses during the early stages of endosymbiosis, this process slowed down significantly, resulting in a conserved gene content across extant taxa. Chromatophore genes faced relaxed selection when compared to homologs in free-living alpha-cyanobacteria, likely reflecting the homogeneous intracellular environment of the Paulinella host. Comparison of nucleotide substitution and insertion/deletion events among different P. micropora strains demonstrates that increases in AT-content and genome reduction are ongoing and dynamic processes in chromatophore evolution.
Novel RU486 (mifepristone) analogues with increased activity against Venezuelan Equine Encephalitis Virus but reduced progesterone receptor antagonistic activity
Authors: DeBono Aaron , Thomas David R. , Lundberg Lindsay , Pinkham Chelsea , Cao Ying , Graham J. Dinny , Clarke Christine L. , Wagstaff Kylie M. , Shechter Sharon , Kehn-Hall Kylene , Jans David A.
Published: February 2019

There are currently no therapeutics to treat infection with the alphavirus Venezuelan equine encephalitis virus (VEEV), which causes flu-like symptoms leading to neurological symptoms in up to 14% of cases. Large outbreaks of VEEV can result in 10,000 s of human cases and mass equine death. We previously showed that mifepristone (RU486) has anti-VEEV activity (EC50 = 20 μM) and only limited cytotoxicity (CC50 > 100 μM), but a limitation in its use is its abortifacient activity resulting from its ability to antagonize the progesterone receptor (PR). Here we generate a suite of new mifepristone analogues with enhanced antiviral properties, succeeding in achieving >11-fold improvement in anti-VEEV activity with no detectable increase in toxicity. Importantly, we were able to derive a lead compound with an EC50 of 7.2 µM and no detectable PR antagonism activity. Finally, based on our SAR analysis we propose avenues for the further development of these analogues as safe and effective anti-VEEV agents.
Enhancing the sensitivity of micro magnetic resonance relaxometry detection of low parasitemia Plasmodium falciparum in human blood
Authors: Thamarath Smitha Surendran , Xiong Aoli , Lin Po-Han , Preiser Peter Rainer , Han Jongyoon
Published: February 2019

Upon Plasmodium falciparum infection of the red blood cells (RBCs), the parasite replicates and consumes haemoglobin resulting in the release of free heme which is rapidly converted to hemozoin crystallites. The bulk magnetic susceptibility of infected RBCs (iRBCs) is changed due to ferric (Fe3+) paramagnetic state in hemozoin crystallites which induce a measurable change in spin-spin relaxation (transverse relaxation) rate in proton nuclear magnetic resonance (NMR) of iRBCs. Earlier, our group reported that this transverse relaxation rate (R2) can be measured by an inexpensive, portable 0.5 Tesla bench top magnetic resonance relaxometry (MRR) system with minimum sample preparation and is able to detect very low levels of parasitemia in both blood cultures as well as animal models. However, it was challenging to diagnose malaria in human blood using MRR, mainly due to the inherent variation of R2 values of clinical blood samples, caused by many physiological and genotypic differences not related to the parasite infection. To resolve the problem of baseline R2 rates, we have developed an improved lysis protocol for removing confounding molecular and cellular background for MRR detection. With this new protocol and by processing larger volume of blood (>1 ml), we are able to reliably detect very low level of parasitemia (representing early stage of infection, ~0.0001%) with a stable baseline and improved sensitivity using the current MRR system.
Eigenvalues of the covariance matrix as early warning signals for critical transitions in ecological systems
Authors: Chen Shiyang , O’Dea Eamon B. , Drake John M. , Epureanu Bogdan I.
Published: February 2019

Many ecological systems are subject critical transitions, which are abrupt changes to contrasting states triggered by small changes in some key component of the system. Temporal early warning signals such as the variance of a time series, and spatial early warning signals such as the spatial correlation in a snapshot of the system’s state, have been proposed to forecast critical transitions. However, temporal early warning signals do not take the spatial pattern into account, and past spatial indicators only examine one snapshot at a time. In this study, we propose the use of eigenvalues of the covariance matrix of multiple time series as early warning signals. We first show theoretically why these indicators may increase as the system moves closer to the critical transition. Then, we apply the method to simulated data from several spatial ecological models to demonstrate the method’s applicability. This method has the advantage that it takes into account only the fluctuations of the system about its equilibrium, thus eliminating the effects of any change in equilibrium values. The eigenvector associated with the largest eigenvalue of the covariance matrix is helpful for identifying the regions that are most vulnerable to the critical transition.
Estimation of the effective reproduction number of influenza based on weekly reports in Miyazaki Prefecture
Authors: Yamauchi Takenori , Takeuchi Shouhei , Yamano Yuko , Kuroda Yoshiki , Nakadate Toshio
Published: February 2019

In Japan, as part of surveillance for seasonal influenza, the number of patients per influenza sentinel site is counted on a weekly basis. Currently, reference values are set for the weekly reported number of influenza cases per sentinel, and pre-epidemic and epidemic warnings are issued based on these values. In this study, we examined the association between these reference values and the effective reproduction number (Rt) using surveillance data for Miyazaki Prefecture collected from 2010 to 2011. There are nine public health centre jurisdictions in this prefecture, and Rt exceeded 1.0 at the time when pre-epidemic warnings were issued in almost all the jurisdictions. Thus, it was indicated that the validity of the reference value was also high for influenza transmission. However, our results indicated the presence of secondary epidemic caused by infections originating both from other jurisdictions and inner jurisdictions, and it is occasionally not possible to evaluate the end of an epidemic in a jurisdiction using only the reference value of termination. It is necessary to establish new methods after considering the situation in the surrounding jurisdictions for more detailed epidemic predictions.
Biphasic changes in spontaneous cardiovagal baroreflex sensitivity during passive hyperthermia
Authors: Turcani Marian , Ghadhanfar Elham
Published: February 2019

Successful adaptation to passive hyperthermia requires continual adjustment of circulation, which is mediated mainly by the autonomic nervous system. The goal of this study was to explore the alterations in spontaneous cardiovagal baroreflex sensitivity (BRS) during exposure to a hot environment. To continuously follow changes in core body temperature (Tc), haemodynamics, and BRS, male Wistar-Kyoto rats were implanted with telemetric transmitters. BRS at an ambient temperature of 23 °C was not steady but oscillated with a maximum power in the range of 0.02–0.2 Hz. Exposure to hot air immediately shifted the distribution of BRS to higher values, although Tc remained unchanged (37.2 (0.3) °C), and the average BRS changed from 1.3 (0.3) to 3 (1.4) ms.mmHg−1, p < 0.0001. The degree of initial cardiovagal baroreflex sensitization explained 57% of the variability in the time to the onset of arterial pressure decline (p = 0.0114). With an increasing Tc (>38.8 (0.6) °C), BRS non-linearly declined, but haemodynamic parameters remained stable even above a Tc of 42 °C when the cardiovagal baroreflex was virtually non-operative. Abrupt full desensitization of the cardiovagal baroreflex with a muscarinic blocker did not induce arterial pressure decline. Our data indicate that a progressive decrease in BRS during passive hyperthermia does not induce haemodynamic instability. The positive association between initial cardiovagal baroreflex sensitization and the time to the onset of arterial pressure decline may reflect the potential protective role of parasympathetic activation during exposure to a hot environment.
The promiscuous activity of alpha-amylase in biodegradation of low-density polyethylene in a polymer-starch blend
Authors: Karimi M. , Biria D.
Published: February 2019

Blending polyolefins with certain types of natural polymers like starch can be beneficial to their biodegradation. The impact of alpha-amylase on the biodegradation of low-density polyethylene (LDPE)-starch blend samples in an aqueous solution was investigated through characterizing their physical, mechanical and chemical properties. Results indicated that the weight and tensile strength of the enzyme treated samples were reduced by 48% and 87% respectively. Moreover, differential scanning calorimetry (DSC) showed an increase in fusion enthalpy of degraded samples which means that the crystallinity has been increased. The biodegradation of LLDPE appeared in Fourier-transform infrared spectroscopy (FT-IR) through the reduction in the intensity of the related peaks. This observation was supported by energy dispersive x-ray spectroscopy (EDXS) analysis where decreasing the percentage of carbon atoms in the treated blend was obtained. Likewise, the gel permeation chromatography (GPC) results pointed to a significant reduction in both the molecular weight and viscosity of LDPE more than 70% and 60% respectively. Furthermore, thermal gravimetric analysis (TGA) affirmed the function of amylase in degradation of the blend. On the basis of the obtained results, it can be claimed that the main backbone of the polymer, as well as the side branches, have been scissored by the enzyme activity. In other words, alpha-amylase has a promiscuous cometabolic effect on biodegradation of LDPE in polymer-starch blends.
Climate and symbioses with ants modulate leaf/stem scaling in epiphytes
Authors: Chomicki Guillaume , Renner Susanne S.
Published: February 2019

In most seed plants, leaf size is isometrically related to stem cross-sectional area, a relationship referred to as Corner’s rule. When stems or leaves acquire a new function, for instance in ant-plant species with hollow stems occupied by ants, their scaling is expected to change. Here we use a lineage of epiphytic ant-plants to test how the evolution of ant-nesting structures in species with different levels of symbiotic dependence has impacted leaf/stem scaling. We expected that leaf size would correlate mostly with climate, while stem diameter would change with domatium evolution. Using a trait dataset from 286 herbarium specimens, field and greenhouse observations, climatic data, and a range of phylogenetic-comparative analyses, we detected significant shifts in leaf/stem scaling, mirroring the evolution of specialized symbioses. Our analyses support both predictions, namely that stem diameter change is tied to symbiosis evolution (ant-nesting structures), while leaf size is independently correlated with rainfall variables. Our study highlights how independent and divergent selective pressures can alter allometry. Because shifts in scaling relationships can impact the costs and benefits of mutualisms, studying allometry in mutualistic interactions may shed unexpected light on the stability of cooperation among species.
Leukocyte–mimicking Pluronic–lipid nanovesicle hybrids inhibit the growth and metastasis of breast cancer
Authors: Chen Qinyue , Chen Yiting , Sun Yali , He Wenxiu , Han Xiaoli , Lu Enhao , Sha Xianyi
Published: February 2019

We have constructed a novel biomimetic Pluronic-lipid nanovesicle hybrid that mimics leukocytes, to target breast cancer and suppress metastasis.
Direct evidence of 2H hexagonal Si in Si nanowires
Authors: He Zhanbing , Maurice Jean-Luc , Li Qikai , Pribat Didier
Published: February 2019

Hexagonal Si (2H polytype) has attracted great interest because of its unique physical properties and wide range of potential applications. Here, through the use of atomic resolution high-angle annular dark-field scanning transmission electron microscopy, we unambiguously report the coherent intergrowth of diamond cubic (3C polytype) and 2H hexagonal Si in a silicon nanowire grown by chemical vapor deposition.
Na2S-promoted reduction of azides in water: synthesis of pyrazolopyridines in one pot and evaluation of antimicrobial activity
Authors: Kale Ashok , Medishetti Nagaraju , Kanugala Sirisha , C Ganesh Kumar , Atmakur Krishnaiah
Published: February 2019

Reduction of various azides using Na2S has been accomplished in water, and, in situ, the resulting amines on reaction with various ketones lead to pyrazolo[3,4-b]pyridines in one pot.
Interfacial competition between a borophene-based cathode and electrolyte for the multiple-sulfide immobilization of a lithium sulfur battery
Authors: Rao Dewei , Liu Xiaojing , Yang Huan , Zhang Linyan , Qiao Guanjun , Shen Xiangqian , Xiaohong Yan , Wang Gongming , Lu Ruifeng
Published: February 2019

The polarized surfaces of borophenes provide appropriate sites to immobilize polysulfides, even under conditions of 300 K and high sulfur loading.
Self-assembled monolayers of chiral periodic mesoporous organosilica as a stimuli responsive local drug delivery system
Authors: Motealleh Andisheh , Dorri Pooya , Kehr Nermin Seda
Published: February 2019

pH responsive PMOs deliver higher dosages of drugs to malignant cells while delivering less of the drugs to healthy cells.
Dinuclear lanthanide complexes supported by a hybrid salicylaldiminato/calix[4]arene-ligand: synthesis, structure, and magnetic and luminescence properties of (HNEt3)[Ln2(HL)(L)] (Ln = SmIII, EuIII, GdIII, TbIII)
Authors: Ullmann Steve , Hahn Peter , Blömer Laura , Mehnert Anne , Laube Christian , Abel Bernd , Kersting Berthold
Published: February 2019

Salicylaldimine/calix[4]arenes support dinuclear, triply bridged, luminescent, lanthanide complexes.
A switchable NO-releasing nanomedicine for enhanced cancer therapy and inhibition of metastasis
Authors: Xu Yan , Ren Hao , Liu Jiwei , Wang Yonglu , Meng Zhengjie , He Zhanjie , Miao Wenjun , Chen Guoguang , Li Xueming
Published: February 2019

Clinical chemotherapy for cancer is limited by the physiological barrier of tumors, resulting in low drug delivery to tumors, poor efficacy of drugs and inability to block tumor metastasis.
Correction: CpG incorporated DNA microparticles for elevated immune stimulation for antigen presenting cells
Authors: Jung Heejung , Kim Dajeong , Kang Yoon Young , Kim Hyejin , Lee Jong Bum , Mok Hyejung
Published: February 2019

Correction for ‘CpG incorporated DNA microparticles for elevated immune stimulation for antigen presenting cells’ by Heejung Jung et al., RSC Adv., 2018, 8, 6608–6615.
High performance opaque and semi-transparent organic solar cells with good tolerance to film thickness realized by a unique solid additive
Authors: Du Xiaoyang , Li Xinrui , Lin Hui , Zhou Lei , Zheng Caijun , Tao Silu
Published: February 2019

The novel solid additive DDO endows organic solar cells with high efficiency, excellent thermostability and good tolerance to film thickness.
A non-enzymatic glucose sensor based on a CoNi2Se4/rGO nanocomposite with ultrahigh sensitivity at low working potential
Authors: Amin Bahareh Golrokh , Masud Jahangir , Nath Manashi
Published: February 2019

A CoNi2Se4–rGO nanocomposite fabricated on Ni foam shows excellent efficiency for non-enzymatic glucose sensing at low applied potential.
Detection and localisation of hesitant steps in people with Alzheimer's disease navigating routes of varying complexity
Authors: McCarthy Ian , Suzuki Tatsuto , Holloway Catherine , Poole Teresa , Frost Chris , Carton Amelia , Tyler Nick , Crutch Sebastian , Yong Keir
Published: February 2019

People with Alzheimer's disease (AD) have characteristic problems navigating everyday environments. While patients may exhibit abnormal gait parameters, adaptive gait irregularities when navigating environments are little explored or understood. The aim of this study was to assess adaptive locomotor responses of AD subjects in a complex environment requiring spatial navigation. A controlled environment of three corridors was set up: straight (I), U‐shaped (U) and dog‐leg (S). Participants were asked to walk along corridors as part of a counterbalanced repeated‐measures design. Three groups were studied: 11 people with posterior cortical atrophy (PCA), 10 with typical Alzheimer's disease (tAD) and 13 controls. Spatio‐temporal gait parameters and position within the corridors were monitored with shoe‐mounted inertial measurement units (IMUs). Hesitant steps were identified from statistical analysis of the distribution of step time data. Walking paths were generated from position data calculated by double integration of IMU acceleration. People with PCA and tAD had similar gait characteristics, having shorter steps and longer step times than controls. Hesitant steps tended to be clustered within certain regions of the walking paths. IMUs enabled identification of key gait characteristics in this clinical population (step time, length and step hesitancy) and environmental conditions (route complexity) modifying their expression.
Base types selection of PSS based on a priori algorithm and knowledge‐based ANN
Authors: Zhang Zaifang , Chai Nana , Liu Yuan , Xia Beixin
Published: February 2019

Manufacturers tend to bundle a product with its related services as a product service system (PSS), to create more values for customers and gain competitive advantages for themselves. Configuration design is the key process of PSS development. Configuring a PSS involves selecting and combining appropriate product and service components, to satisfy individual customer requirements. This study studies the mapping relationship between customer requirement attributes and PSS base types in PSS for CNC machine tools, which provides a great reference value for engineers in configuration design. Owing to the high complexity and non‐linearity between customer requirement and product, an integrated intelligent learning method based on a priori algorithm and knowledge‐based artificial neural network (ANN) is proposed in this study. First, the data of historical configuration instance data sets are processed and then a priori algorithm is used to extract the effective rules as domain knowledge. Domain knowledge is used to build the initial structure of ANN. Moreover, data sets are used to further optimize the network. The knowledge‐based ANN is used to realize the mapping between customer requirement attributes and PSS base types. The proposed method is validated in the selection of the PSS base type for CNC machine tools.
Insulation protection and online stress agent identification for electric machines using artificial intelligence
Authors: Guedes Armando Souza , Silva Sidelmo Magalhaes
Published: February 2019

Insulation failures are among the most important problems affecting electric machines. Although standard procedures are widely used to assess the insulation condition of these machines, no alternative is available to allow the identification of the stress agents affecting the insulation system. Another limitation of the standard procedures is the fact that they are based on tests that require the interruption of the operation of the machine. This study presents a technique that allows the online assessment and protection of the insulation of low‐ and medium‐voltage electric machines, along with the identification of the stress agents responsible for the degradation of the insulation. The proposed technique is based on the use of a highly sensitive current transformer, an algorithm to identify the most affected phase, and an artificial neural network to indicate the stress agent affecting the machine. The presented experimental results show that the proposed system can identify thermal degradation, moisture absorption and contamination by oil. The low current levels that can be measured by the developed system enable the application of the proposed technique to low‐ and medium‐voltage machines.
Influence of static eccentricity on unbalanced magnetic force of external rotor permanent magnet brushless direct current motor used as In‐wheel motor
Authors: Ma Conggan , Cui Hongwei , Zheng Ping , Zhang Yuying , Gao Haibo
Published: February 2019

Here, analytical expressions of the unbalanced magnetic force (UMF）of the stator and the rotor under static eccentricity (SE) are deduced by using complex relative magnetic conductivity method and Maxwell stress tensor method. The frequency characteristics of the UMF are obtained. Further the influence of different eccentricity ratio on the UMF is researched. Then, an external rotor permanent magnet brushless direct current motor (PMBLDCM) with 46 poles and 51 slots used as an in‐wheel motor is taken as an example to verify the frequency characteristics by finite element analysis (FEA). The research shows that the frequency characteristics of the UMF of the stator s related to electric frequency. The frequency characteristics of the UMF of the rotor are related to the power source frequency and the rotation frequency of the wheel. It does not introduce new frequency components when the motor SE occurs. As the SE ratio increases, the amplitude of the UMF increases. The UMF without eccentricity exists in all directions with the change of the time. However, as the eccentricity ratio increases, the direction of the UMF is closer to the eccentric direction.
Developing three‐dimensional‐phase surface‐based wide area protection centre in a smart grid with renewable resources
Authors: Eissa Moustafa M
Published: February 2019

The complexity of interconnection modern power systems has made them more subject to wide area disturbances that have contributed to several failures of system protection that operate as a standalone and with the multi‐zones operation. The high penetration of doubly‐fed‐induction‐generator wind farms in power grid has a negative impact on the operation of the modern system protection while the sensing components of the current signals decay rapidly due to the high crowbar resistance during fault events. Such cases can drop the relays that operate in standalone mode and depend on the current magnitude only. Standalone relays are not a proper solution for the future of protecting large‐scale interconnected grid. Wide area monitoring has been developed to enhance the protection schemes but unfortunately it is limited to backup protection application and also work in standalone mode. More than 70% of the wide area disturbances are caused by relay mal‐operation due to protection settings and miss‐coordination. The concept of the idea does not depend on the short‐circuit current magnitude and operates as one‐zone. The developed idea is based on describing the dynamic operation of the lines before and after the faults using differential‐equations. The differential equations are solved through orbits movement in a phase‐diagram.